Epidermal Coverage of Traumatic Wound Injuries Via Use of Autologous Skin Cell Harvesting Device in Combination With Widened Meshed Autograft Applied Over Bilayered Wound Matrix
Phase: NA
Conditions: Wounds and Injury
Sponsor: Rubin, J. Peter, MD

 
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Protocol Title: Epidermal Coverage of Traumatic Wound Injuries via Use of 
  Autologous Skin Cell Harvesting Device in Combination with Widened Meshed Autograft 
  Applied Over Bilayered Wound Matrix 
 
NCT02469168 
 
Study Protocol including statistical plan 
 
Approved V4 09-04-15 
 
 

 
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WALTER REED NATIONAL MILITARY MEDICAL CENTER (WRNMMC) 
BETHESDA, MD 
 
1. GENERAL INFORMATION 
 
  1.1 Protocol Title: Epidermal Coverage of Traumatic Wound Injuries via Use of 
  Autologous Skin Cell Harvesting Device in Combination with Widened Meshed Autograft 
  Applied Over Bilayered Wound Matrix 
  
1.2 Principal Investigator (PI) 
LTC Leon J. Nesti, MC, USA 
Associate Professor, USUHS 
Chief, Clinical and Experimental Orthopaedics 
Uniformed Services University of the Health Sciences (USUHS) 
4301 Jones Bridge Rd. Bethesda, MD 20814 
Hand and Upper Extremity Reconstructive Surgeon 
Department of Orthopaedics 
Walter Reed National Military Medical Center (WRNMMC) 
8901 Wisconsin Ave. Bethesda, MD 20889 
Phone: (240) 994-7347 
E-mail: Leon.J.Nesti.mil@mail.mil 
Directorate: Surgery 
Responsibilities: Will be responsible for protocol development, adherence and execution, 
passage of the protocol through the local IRB, overall data integrity, applying for and 
receiving approval for any modifications to the protocol or informed consent form, 
training of associate investigators, ensuring safety of the volunteers, reporting of any AEs 
or protocol deviations, full accountability and proper storage of the investigational device, 
interpretation of study data results and presentation and preparation of manuscripts. The 
PI assures overall coordination of the study and the filing of a final clinical study report 
with the Sponsor. 
 
1.3 Associate Investigator(s) 
COL Barry Martin, MC, USA 
Chief of Plastic and Reconstructive Surgery Service 
Department of Surgery 
Walter Reed National Military Medical Center (WRNMMC) 
8901 Wisconsin Ave Bethesda, MD 20889 
Phone: 301-319-4226 
E-mail: Barry.D.Martin2.mil@mail.mil 
Directorate: Surgery 
Responsibilities: Identification and enrollment of study subjects; will provide and/or assist 
with surgical intervention including use of the investigational device, provide input and 
expertise; clinical evaluator of surgical outcomes as needed; will assist PI and Sponsor with 
interpretation of study data results and presentation and preparation of manuscripts.   
DATES OF INVOLVEMENT: Sept 2013 to study completion 
 
LtCol Kerry Latham, MC, USAF 
Staff Plastic Surgeon  

 
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Director, Walter Reed National Military Medical Center Craniofacial Team 
Plastic and Reconstructive Surgery Service 
Department of Surgery 
Walter Reed National Military Medical Center (WRNMMC) 
8901 Wisconsin Ave Bethesda, MD 20889 
Phone: 301-319-4226 
E-mail: kerry.p.latham.mil@mail.mil 
Directorate: Surgery 
Responsibilities: Identification and enrollment of study subjects; will provide and/or assist 
with surgical intervention including use of the investigational device, provide input and 
expertise; clinical evaluator of surgical outcomes as needed; will assist PI and Sponsor with 
interpretation of study data results and presentation and preparation of manuscripts.   
DATES OF INVOLVEMENT: Sept 2015 to study completion 
 
LTC Jon H. Meyerle, MC, USA 
Division Chief, Immunodermatology 
Department of Dermatology 
Walter Reed National Military Medical Center (WRNMMC) 
8901 Wisconsin Ave Bethesda, MD 20889 
Phone: 301-319-2449 
E-mail: Jon.Meyerle@usuhs.edu 
Responsibilities: Provide input and expertise; clinical evaluator of surgical outcomes. 
Will not be directly involved in treating the subject; will perform assessments for 
healing/scar evaluation via Vancouver Scar Scale (VSS) and the Patient and Observer 
Scar Assessment Scale (POSAS) (will be blinded to treatment provided at the target 
wound site). 
DATES OF INVOLVEMENT: Sept 2013 to study completion 
 
LTC Jason D. Marquart, MC, USA 
Chief of Dermatology Service 
Director of Procedural Dermatology Division 
Department of Medicine 
Walter Reed National Military Medical Center (WRNMMC) 
8901 Wisconsin Ave Bethesda, MD 20889 
Phone: 301-295-4551 
E-mail: Jason.D.Marquart2.mil@mail.mil 
Directorate: Medicine 
Responsibilities: Provide input and expertise; clinical evaluator of surgical outcomes. 
Will not be directly involved in treating the subject; will perform assessments for 
healing/scar evaluation via Vancouver Scar Scale (VSS) and the Patient and Observer 
Scar Assessment Scale (POSAS) (will be blinded to treatment provided at the target 
wound site).  
DATES OF INVOLVEMENT: Sept 2013 to study completion 
 
Nancy E. Lee, BA 
Contractor: Geneva Foundation, Research Associate/Coordinator 
Department of Orthopaedics 
Walter Reed National Military Medical Center (WRNMMC)  

 
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8901 Wisconsin Ave Bethesda, MD 20889 
Phone: 240-372-9513 
E-mail: Nancy.Lee36.ctr@mail.mil 
Directorate: Surgery 
Responsibilities: Study coordinator, regulatory submission and communication with IRB 
and Sponsor, recruitment, obtain consent, perform/review screening evaluations, 
implementation of study protocol, data collection and analysis, query resolution, monitor 
subject for adverse event occurrences, assists with development of study reports (initial, 
continuing review and final) 
DATES OF INVOLVEMENT: March 2013 to study completion 
 
   1.4 Collaborators/Consultants 
  James Holmes, IV, MD 
Medical Advisor 
Wake Forest School of Medicine 
Institute for Regenerative Medicine 
Richard H. Dean Biomedical 
Building 391 Technology Way 
Winston-Salem, NC 27101  
Phone: 336-716-2255 
Email: jholmes@wakehealth.edu 
Directorate: Not Applicable 
Responsibilities: Subject matter expert in regenerative medicine and the use of the ReCell 
device for the treatment of burns 
DATES OF INVOLVEMENT: Feb 2013 to study completion 
 
Kimberly Strohkirch, MSEE 
Regulatory Consultant 
Memphis Regulatory Consulting, LLC (MRC) 
3786 Russell Hurst Drive W 
Memphis, TN 38135 
Phone: 901-361-2037 
Email: strohkirch@memphisregulatory.com 
Directorate: Not Applicable 
Responsibilities: Regulatory affairs consultant.  Assist with FDA IDE preparation as 
needed. 
DATES OF INVOLVEMENT: Feb 2013 to study completion 
 
Sandy Maddock, RN, BSN, MSHS, CCRA 
President 
IMARC Research, Inc. 
22560 Lunn Road 
Strongsville, OH 44149 
Phone: 440-801-1540 
Email: SMaddock@imarcresearch.com 
Website: www.imarcresearch.com 
Directorate: Not Applicable 
Responsibilities: Contract Research Organization (CRO) which will be providing clinical 

 
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monitoring and auditing oversight. Collective monitoring activities will be provided to 
assist study site in compliance with the protocol, the signed agreement, IRB 
requirements, and applicable FDA regulations in an effort to ensure human subject 
protection. 
DATES OF INVOLVEMENT: July 2013 to study completion 
 
J. Peter Rubin, MD 
Director, Center for Innovation in Restorative Medicine (CIRM)  
University of Pittsburgh School of Medicine 
690 Scaife Hall 
3550 Terrace Street 
Pittsburgh, PA 15261 
Phone: 412-383-8080 
Email: rubipi@upmc.edu 
Directorate: Not Applicable  
Responsibilities: Sponsor of the IDE (will hold IDE), will retain overall responsibility 
for the progress of the clinical trial and will ensure that it is conducted, recorded and 
reported in accordance with the protocol, SOPs, GCP and regulatory requirements to 
assure the protection of human subjects and data integrity.  Will submit IDE application 
to FDA as well as prompt reporting of safety reports to the FDA.  
Additional Responsibilities: Data Coordinating Center (housing of data), will be 
accountable for maintaining oversight of all data management activities to ensure data 
quality and integrity with accurate reporting, interpretation and verification, and will 
ensure systems and procedures are in place for the protection and safeguarding of 
confidentiality of records. 
DATES OF INVOLVEMENT: Feb 2013 to study completion 
 
Patsy Simon, RN, BSN, CCRC 
Director, Regulatory and Clinical Affairs UPMC Center for 
Innovation in Restorative Medicine (CIRM) Department of 
Plastic Surgery University of Pittsburgh 
University of Pittsburgh School of Medicine 
225 University Center 
120 Lytton Avenue 
Pittsburgh, PA 15213 
Phone: 412-864-2580 
Email: simonpa@upmc.edu 
Directorate: Not Applicable 
Responsibilities: Will provide direct management and operational aspects for the FDA 
IDE and local Institutional Review Board regulatory process and data management of the 
clinical trial. This includes assisting with development of clinical practice, SOP 
generation and clinical procedural process specific to the site while adhering to 
all levels of regulatory regulation and guidance, clinical trial conduct and data 
compliance with primary focus on good clinical practice. 
DATES OF INVOLVEMENT: Fall 2012 to study completion 
 
Patrick Cantini 
OSD Program Manager 

 
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Director, Scientific Collaborations 
McGowan Institute for Regenerative Medicine 
450 Technology Drive, Suite 300 
Pittsburgh, PA 15219 
Phone: 412-624-5209 
Email: cantinip@upmc.edu 
Directorate: Not Applicable 
Responsibilities: Will be responsible for all aspects of project planning, direction, 
and development. Additionally, will serve as the primary administrative liaison for 
this project and will coordinate the myriad of activities to support a seamless 
interface with WRNMMC, Geneva, ReCell (Avita) and other collaborators. 
DATES OF INVOLVEMENT: Fall 2012 to study completion 
 
Dale Glaser, Ph.D  
Glaser Consulting  
3115 4th Avenue 
San Diego, CA 92103  
Phone: 619-220-0602 
Fax: 619-220-0412 
Email: glaserconsult@sbcglobal.net 
Website: www.glaserconsult.com  
Directorate: Not Applicable  
Responsibilities: Biostatistical support 
DATES OF INVOLVEMENT: Oct 2013 to 
study completion 
 
Andrew Quick, MS 
Avita Medical Americas, LLC  
9221 Corbin Ave, Suite 220 
Northridge, CA 91324-2494 
Phone: 818-698 8345 
Email: aquick@avitamedical.com  
Directorate: Not Applicable 
Responsibilities: Vendor agreement for the procurement of the ReCell Autologous Cell 
Harvesting Device that will be used for the proposed intervention. Will also provide 
training on device use for study team members 
DATES OF INVOLVEMENT: Feb 2013 to study completion 
 
  1.5 Medical Research Monitor  
Carlton Q. Brown, M.D.  
Attending Anesthesiologist, Anesthesiology Service 
  Department of Surgery 
  Walter Reed National Military Medical Center (WRNMMC) 
8901 Wisconsin Ave Bethesda, MD 20889 
Phone: (301) 295-4455 x166 
Email: Carlton.Q.Brown.ctr@mail.mil 
Directorate: Surgery 
RESPONSIBILITIES: To provide safety monitoring of research subjects for 

 
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conditions that may arise during the conduct of the study including the authority to 
remove human subjects from the study and take any other actions necessary to protect 
the subjects of the study.  Duties may include discussion of the protocol with the 
investigators, review study monitoring plans, data collection and analysis, interview 
human subjects, and consult with others outside the protocol about the research and 
make recommendations on changes to the informed consent process based on the 
review of study events. All adverse events will be reviewed and signed off on by the 
research monitor. Any observations and findings considered unanticipated problems 
involving risk to subjects will be promptly reported to the Institutional Review Board 
(IRB), the Human Research Protection Office (HRPO), the Human Protections 
Administrator (HPA), or the Institutional Official as deemed appropriate. 
Additionally, will review and sign substantial submissions to the IRB.  If necessary, 
shall have authority to stop this clinical trial, remove subjects and take whatever steps 
needed to protect the safety and well-being of human subjects until the IRB can assess 
the monitor’s report. 
DATES OF INVOLVEMENT: June 2013 to study completion 
 
      1.6 Outside Laboratory Facility    
    Annapath, Inc. 
Sachin Shetty, President 
4801 Telsa Drive, Suite H 
Bowie, MD 20715 
Phone: 301-352-6100 or 410-370-0836 
Fax: 301-352-6300 
Email: sachinshetty_us@yahoo.com 
Directorate: Not Applicable 
Responsibilities: Processing of biopsy specimens to include grossing, processing 
(staining), embedding into paraffin blocks and slide preparation (Note: Histology 
assessments will be performed by a dermatopathologist at WRNMMC) 
DATES OF INVOLVEMENT: Fall 2013 to study completion 
 
 

 
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Study Team Responsibilities 
Principal 
Investigator 
Associate 
Investigator 
Collaborator 
▪ 
Study design and general coordination of research 
X 
X 
▪ 
Provide access to subjects 
X 
X 
▪ 
Recruit eligible subjects 
X 
X 
▪ 
Screen eligible subjects 
X 
X 
▪ 
Obtain informed consent 
X 
X 
▪ 
Obtain Health Insurance Portability and 
Accountability Act (HIPAA) Authorizations from 
participants 
X 
X 
▪ 
Conduct research procedures involving direct 
interaction with subjects 
X 
X 
▪ 
Clinical laboratory tests or support 
X 
X 
▪ 
Research laboratory assays, tests, or support 
X 
X 
▪ 
Pharmacy support (i.e. storage, inventory, and 
dispensing of all investigational drugs used in the 
research) 
X 
▪ 
Data entry (eCRFs at WRNMMC; 
database UPitt/UPMC) 
X 
X 
X 
▪ 
Data analysis 
X 
X 
X 
▪ 
Retain/share research data 
X 
X 
X 
▪ 
Retention of research protocol documents 
(including consent/information sheets) 
X 
X 
▪ 
Retention of HIPAA documentation, including 
HIPAA authorization or other HIPAA templates 
with required representations from PI 
X 
X 
▪ 
Retain/share specimens for current research 
X 
X 
X 
▪ 
Reporting to appropriate IRB(s), institutional 
officials, and /or sponsor - unanticipated problems 
involving risks to subjects or others, adverse 
events, and serious or continuing non-compliance 
X 
X 
X 
▪ 
Establishing procedures to ensure subject privacy 
and confidentiality of research data (DoD 
6025.18R; 45 CFR 160 and 164). 
X 
X 
▪ 
Submission of Continuing Review reports for IRB 
review 
X 
X 
▪ 
Establish a plan for the destruction of research 
data containing identifiers or for the retention of 
the identifiers for public health or research 
purposes or as otherwise required by law 
X 
X 
▪ 
Post-approval monitoring of the conduct of the 
research 
X 
X 
X 
▪ 
Data monitoring plan – coordination and 
communication 
X 
X 
X 
▪ 
Clearance of research-related publications or 
presentations 
X 
X 
▪ 
Training of ReCell device, provide investigational 
ReCell device kits 
X 
▪ 
Sponsor for IDE 
X 
 

 
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 ABSTRACT 
 
2.1 Purpose 
The purpose of this investigation is to evaluate the safety, tolerability, preliminary and 
long-term effectiveness of utilizing the ReCell Autologous Cell Harvesting Device 
(ReCell) combined with widened split-thickness skin graft (STSG) mesh onto the 
dermal regenerate INTEGRA™ Meshed Bilayer Wound Matrix (MBWM) for healing 
of full-thickness wounds. 
 
2.2 Research Design 
The proposed study is a prospective, single-center, randomized within-patient controlled 
feasibility study to evaluate the safety, tolerability, preliminary and long-term effectiveness 
of the ReCell Device for re-epithelialization (healing) of full-thickness wounds following 
previously successful treatment with INTEGRA™ MBWM. 
 
2.3 Methodology /Technical Approach 
In the proposed study, each patient will serve as his/her own control. Due to the nature 
of the study, only patients whose wounds have been previously successfully treated 
with INTEGRA™ MBWM as part of their standard of care will qualify for 
participation. 
 
Therefore, as part of enrollment eligibility criteria for this study, the identified study 
wound will first be treated with INTEGRA™ MBWM. The wound will then be allowed 
to heal for approximately two to four weeks, at which time a viable granulation layer 
will have developed thus allowing for next stage STSG grafting. The timing of the 
STSG application will be determined by clinician judgment based on the state of the 
granulation process, which varies between patients, but typically takes 2 to 4 weeks. 
 
Approximately two to four weeks after INTEGRA™ MBWM treatment, the studied 
wound will be divided into a ReCell-treated area (over 1:5 meshed STSG) and a control 
area treated with 1:1.5 meshed STSG (no ReCell).  In all cases, the ReCell region may 
be up to 320cm2 in size; the upper limit of application area for one ReCell kit, with a 
similarly sized control region.  If the wound is larger than the combined ReCell and 
control regions (over 640cm2), the areas outside the study regions will be designated as 
non-study areas and treated according to standard of care. The same primary and 
secondary dressings will be used on ReCell-treated areas, control areas and donor sites. 
Once the study and control wounds are determined to have healed, standard local 
clinical practice will be followed. 
 
Within-subject comparisons of the ReCell region and control region, in order to 
evaluate improvements associated with use of ReCell, a battery of measurements and 
evaluations will be made.  These measurements are divided into three categories: 
safety and tolerability, preliminary effectiveness (acute healing process) and long-term 
effectiveness. 
 
The safety of research participants is foremost. Therefore, efforts will be made to 
control risks to participants throughout the duration of their study participation. Wound 
healing time, donor site morbidity and histology will be assessed during an acute 6 

 
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week phase, with follow-up visits at Weeks 1, 2, 3, 4 and 6 post-treatment. 
 
Subjects will continue in the study for long-term follow-up with clinic visits at Week 12 
and 24 post-treatment.  Healing of treated wound sites (A region and B region) and 
donor sites (STSG 1:5, STSG 1:1.5 and ReCell) will be assessed at each visit.  Treated 
wounds will be considered healed when 95% or greater of the study area has re-
epithelialized by Week 6 post-treatment.  Donor sites will be considered healed when 
≥95% of the donor site has re-epithelialized by Week 4 post-treatment. Aesthetic and 
functional outcomes of the treated areas will be assessed and documented.  Subject 
satisfaction will also be assessed and documented at these two time points. 
 
3.OBJECTIVES AND SPECIFIC AIMS 
The goal of the study described herein is to determine the safety, tolerability, preliminary 
and long-term effectiveness of the use of the Recell device over a widened STSG mesh.  
It is hypothesized the ReCell cell suspension, in combination with INTEGRA™ MBWM, 
will improve upon the current standard of care. The potential for ReCell’s promotion of 
healing in the interstices of the STSG mesh may close gaps that are potential points of 
failure during subsequent rehabilitation and return to physical activity. Within the  
current study, each participant will serve as his/her own control, allowing for comparison 
of ReCell treated (experimental) and non-ReCell treated (control) regions of the grafted 
wound.  The specific aims of this pilot clinical study are delineated below. 
 
Specific Aim 1: Evaluate safety and tolerability of ReCell treatment of full-thickness 
wounds treated STSG over INTEGRA™ MBWM compared to control site. The safety 
and tolerability of ReCell treatment relative to standard of care (the control site) will be 
evaluated during the first 12 weeks after treatment, when the wound is most vulnerable 
for potential graft failure. Safety-related issues will continue to be monitored through 
24 weeks after treatment. 
 
Participants will be assessed for the following safety issues at each visit: 
 
• 
Delayed healing/non-healing of wound and donor site 
• 
Graft loss 
• 
Heterotopic ossification 
• 
Infection 
• 
Scar contracture 
• 
Durability (i.e. abrasions/injuries at graft site due to graft fragility) 
• 
Allergic response to trypsin (the enzyme used in the ReCell process) 
• 
Subject Complaint (i.e. pain and itching) 
• 
Vital Signs 
• 
Blood chemistries and hematology 
• 
Other Treatment-related adverse events requiring surgical intervention prior to 
Week 12 post-treatment and all serious adverse event (SAE) occurrences 
throughout the study. 
 
We predict non-inferiority in safety measures between ReCell-treated areas and control 

 
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areas of the wound. 
 
Specific Aim 2: Evaluate the preliminary effectiveness of ReCell treatment of full- 
thickness wounds treated with STSG over INTEGRA™ MBWM compared to a control 
site. Preliminary effectiveness will be assessed during an acute healing phase (Week 1– 
6) and will focus on healing of both wound and donor sites. Evaluations to be performed 
include: 
 
• 
Wound epithelialization 
• 
Histology 
• 
Patient pain rating 
 
We predict that, at each time point, more ReCell-treated areas will be healed to an extent 
defined as non-inferior compared to the control areas of the wound. 
 
Specific Aim 3: Evaluate the long-term effectiveness of ReCell treatment of full- 
thickness wounds treated with INTEGRA™ MBWM compared to a control site. Long- 
term effectiveness will be assessed at Weeks 12 and 24 post-ReCell treatment. 
Evaluations will focus on the integrity and durability of regenerated tissue as well as 
physical characteristics such as pliability and cosmesis. Patient satisfaction will also be 
evaluated. Evaluations to be performed include: 
 
• 
Scar assessment scale using the Patient and Observer Scar Assessment Scale 
(POSAS) and Vancouver Scar Scale 
• 
Functional outcome rating 
• 
Patient satisfaction 
• 
Histology 
• 
Radiographic evaluation for assessment of heterotopic ossification 
 
We predict that scar/functional outcomes and patient satisfaction metrics will be non- 
inferior for ReCell treated areas. 
 
INTRODUCTION TO STUDY CONDUCT 
This document is a protocol for a human research study. This study is to be conducted 
according to US and international standards of Good Clinical Practice (International 
Conference on Harmonization ICHE6), the Code of Federal Regulations Title 21 parts 
803 and 812, and other applicable government regulations and Institutional research 
policies and procedures. No amendment to the protocol or deviation from the protocol 
will be implemented without the prior review and approval of the Institutional Review 
Board (IRB) except where it may be necessary to eliminate an immediate hazard to a 
research participant.  In such a case, the deviation will be reported to the IRB as soon as 
possible. 
 
4.BACKGROUND AND SIGNIFICANCE 
 
4.1 Literature Review. 
As survival rates of our war wounded continue to improve through significant advances 

 
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in our military’s forward medical care, the number of complex soft tissue and orthopedic 
extremity injuries present difficult ongoing challenges. Extremity injuries secondary to 
war conflict, especially those caused by improvised explosive devices (IEDs), can result 
in massive soft tissue losses secondary to foreign body contamination, infection-related 
soft tissue necrosis, development of compartment syndromes, and secondary 
requirements for serial debridement and surgical procedures to aid in controlling the 
local wound environments. Often, these extremity injuries lead to significant utilization 
of health care resources not only within the post-trauma inpatient settings, but also 
through the course of the wounded service members extensive rehabilitation 
requirements. 
 
In addition to the direct injury patterns and soft tissue losses experienced within certain 
wounded service members, donor site burdens for their reconstructions can also be rather 
significant.  Many of the wounded service members who suffer from traumatic extremity 
injuries will require advanced reconstructions. These reconstructions typically involve 
complex soft tissue procedures often coupled with orthopedic surgeries to eventually 
cover vital structures and/or the soft tissue defects. Soft tissue injuries require various 
immediate as well as staged reconstructions including but not limited to need for eventual 
skin grafts, local or regional flaps, to advanced techniques such as microsurgical free 
tissue transfers. 
 
Wounds that penetrate deep into the skin (full-thickness) remain a major clinical 
challenge to patients and reconstructive surgeons. Application of split or full-thickness 
skin grafts is associated with significant donor site morbidity (e.g., bleeding and scar 
formation) and often in the severely wounded patient, harvest sites are limited. For this 
reason, there has been much interest in the application of artificial substrates that can be 
used to enhance healing of the full-thickness wound.  One such substrate is the 
INTEGRA™ MBWM (Integra Life Sciences Corporation, USA), a bilayer membrane 
designed to provide immediate coverage of full-thickness wounds. This wound care 
device is comprised of a porous matrix of cross-linked bovine tendon collagen and 
glycosaminoglycans and a semi-permeable polysiloxane (silicone layer). The semi- 
permeable silicone membrane controls water vapor loss, provides a flexible adherent 
covering for the wound surface and adds increased tear and suture retention strength to 
the device. The collagen-glycosaminoglycan biodegradable matrix provides a scaffold for 
dermal cellular invasion and capillary growth. During use, the INTEGRA™ MBWM is 
placed on a surgically debrided or excised wound, providing the needed framework for 
the blood vessels and dermal skin cells to remodel the damaged site. As skin cells migrate 
into the matrix, the collagen is slowly absorbed and replaced with collagen produced 
from the patient’s own cells. In approximately 14 to 28 days, the scaffold is eventually 
remodeled as the patient's cells rebuild the damaged site. Once the dermal cells have 
integrated with the porous matrix, the silicone layer is removed and typically replaced 
with a thin meshed STSG. Application of the meshed STSG over INTEGRA™ MBWM 
is currently the standard care for patients with full-thickness wounds treated at Walter 
Reed National Military Medical Center (WRNMMC). 
 
However, individuals who have sustained a traumatic injury, particularly wounded 
warriors, frequently possess limited donor site availability due to the nature and extent of 
associated injuries. 

 
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Therefore, harvest sites for the STSG are often limited. The ReCell Autologous Cell 
Harvesting Device system allows autologous transplant of the patient’s own skin cells, 
including epidermal progenitor cells using a small thin biopsy site (typically no larger than 
2 cm by 2 cm).  
 
Our primary hypothesis is that when used in combination with a meshed STSG over 
INTEGRA™ MBWM, ReCell will produce non-inferior safety and performance using an 
expanded meshing ratio, thereby decreasing the required donor site and a secondary 
hypothesis of  potential superiority to promote faster healing, minimization of mesh 
patterned scar and overall improved patient quality of life.  
 
4.2 Preliminary Data and/or Findings 
The safety of ReCell has been demonstrated with over 5,000 treatment procedures 
conducted worldwide. ReCell has CE Marking in Europe, TGA clearance in 
Australia, SFDA clearance in China and Health Canada approval as well as 
approval in other markets (e.g., Taiwan, Hong Kong, Mexico, Brazil and 
Venezuela). Case series studies include an 81-patient Australian study (PSR-01 and 
PSR-02) of epidermal replacement due to acute superficial skin injury, unhealed 
donor site, raised scars, or correction of hypopigmentation caused by a previous 
injury or skin resurfacing procedure. These studies included both pediatric and adult 
patients. Effectiveness assessments included: percent re-epithelialization through 6 
weeks post-treatment, clinical assessment of wound appearance at recipient site (e.g., 
healed, not healed), assessment of skin quality by a blinded assessor (photography 
assessment) in terms of color match with the surrounding skin, pigment and texture 
at recipient site, and appearance of scar at donor site in terms of color, pigment and 
texture and degree of scarring. In both studies, minimum follow- up was 26 weeks 
post-treatment. Safety was assessed based on adverse events, vital signs and 
concomitant medication. All wounds achieved healing (≥ 95% re- epithelialization) 
by Week 6.  At the final assessment (Week 52 for PSR-01 and Week 56 for PSR-
02), no wounds were determined to be grossly mismatched to the surrounding 
area with respect to color, pigment, or texture. Within these studies, use of the 
ReCell device in epidermal restructuring was well tolerated and did not show any 
systemic effect. There was no association with any alteration in vital signs. Overall 
the safety profile of ReCell kit observed in these studies demonstrated that the ReCell 
device can be used in patients requiring epidermal restructuring without causing 
any systemic toxicity. 
 
Furthermore, several recent publications report on positive clinical results with 
ReCell in a variety of indications, including deep partial thickness burns [Gravante 
G, et al., 2007], vitiligo [Mulekar SV, et al., 2007] and hypopigmented scarring 
[Goodman GJ, 2008, Cervelli V, et al., 2009, Draaijers LJ, et al., 2004]. 
 
To date, there is no preliminary data applicable for this indication. However, ReCell is 
currently being evaluated in the United States as a primary treatment of partial-thickness 
burns compared with standard split thickness meshed skin grafts in a multi-center clinical 
trial and at Wake Forest School of Medicine, Institute for Regenerative Medicine under 
the direction of Dr. James Holmes, Medical Advisor for this proposed clinical trial. 
Safety monitoring of adverse events reveals application of the ReCell device has been 
well-tolerated and there have been no adverse events which are inconsistent or 
unexpected for the subject population. 
 

 
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4.3 Scientific Justification and Military Relevance 
Significant soft tissue losses due to blast injuries are becoming more common in 
modern warfare. The efforts to manage these wounds are becoming more challenging. 
More than half of the injuries in modern combat are due to explosions; including 
mortars, rockets, and IEDs. The majority of these injuries are to the extremities, 
resulting in significant soft tissue loss and the need for available autologous skin 
sources. Given the complex and massive soft tissue injuries that traumatic blast injuries 
cause in a number of our wounded warriors, improved availability of skin 
regenerative techniques and methods to not only expand autologous skin donor 
sources but also to aid in lessening donor site morbidity is of great interest and 
importance. The ReCell Device is a stand-alone, battery operated regenerative skin 
cell separation device that enables preparation of a cell suspension from a small, thin, 
split-thickness skin biopsy site, thus, providing for great expansion of a limited 
autologous skin donor site. 
 
Additionally, because the autologous epidermal cell suspension is available for 
immediate delivery onto a prepared skin surface at the time of skin donor harvest, the 
need for further cell expansion within the laboratory setting is avoided. The 
performance of ReCell over INTEGRA™ MBWM in combination with 1:5 meshed 
split-thickness skin graft (STSG) will be compared to standard practice control (i.e., 
1:1.5 meshed STSG over INTEGRA™ MBWM), with the ultimate potential benefit 
of earlier re-epithelialization, acceptable durability, and reduction in the risk of 
infection and scarring for those wounds treated with ReCell. 
 
Based on preclinical and early clinical results, the short-term benefits of this study will 
include potential viable and readily available regeneration of necessary autologous 
skin to place on a dermal regenerate in massive soft tissue injuries. This clinical 
model would be the first to potentially show the benefit of such treatments in 
traumatic wounds, outside of burn patients.  It would also have immense benefits - 
both for those military healthcare beneficiaries suffering from soft tissue injuries as 
well as traumatic civilian injuries that likewise pose significant issues with available 
autologous skin coverage (e.g. necrotizing fasciitis, motor vehicle accidents or other 
trauma with associated soft tissue avulsion injuries, etc.).  Important data on the 
mechanism of action, refinements of technique, expansion of the device and technique 
to future applications, and most importantly, technology transfer throughout 
WRNMMC, associated military treatment facilities (MTF), and civilian or academic 
centers is of great interest. 
 
We expect all ReCell treated and control areas of the wounds to heal adequately. 
However, we hypothesize areas treated with ReCell will re-epithelialize more 
quickly than control areas, which has the potential to reduce the risk of infection 
and scarring in ReCell treated areas compared to control areas.  Healing will be 
defined as: 95% or greater re-epithelialization has occurred at area treated by 
Week 6 post-treatment. 
 
4.4 Human Subjects Justification. 
The proposed prospective, non-randomized, within-patient controlled feasibility study 
will enroll 20 military healthcare beneficiaries, both male and female, currently 

 
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receiving treatment for a traumatic wound injury at WRNMMC. The goal of this 
study is to evaluate the safety, tolerability, preliminary and long-term effectiveness of 
the ReCell device for re-epithelialization of full-thickness wounds treated with 
INTEGRA™ MBWM. 
 
Data collected in the completion of the proposed study will support or refute the 
hypothesis that the use of the ReCell device over a widened STSG mesh in combination 
with INTEGRA™ MBWM will improve upon the current standard of care for treating 
full-thickness wounds within the traumatic injury population. We believe that ReCell 
will promote improved healing within the interstices of finely meshed STSG, thus 
improving durability among STSG gaps that are potential points of failure during later 
physical activity. 
 
Furthermore, ReCell will reduce the burden of donor skin graft sites by decreasing 
the amount of autologous skin grafting harvest necessary to cover massive soft tissue. In 
effect, we propose by using the existing standard for dermal regenerate in INTEGRA™ 
MBWM, full thickness wounds will be converted into partial thickness wounds, which 
can then be covered with finely meshed STSG and ReCell regenerative skin expansion 
system to provide more durable stable skin coverage while also reducing donor site 
morbidity and pain. 
 
The impact of scar complications (i.e. pain, itching and fragility), may have impact on 
the quality of life. For the patient, the presence of pain and itching is often more 
disturbing than the actual appearance, and therefore these symptoms have a major 
impact on the quality of life.  Additionally, scar formation can result in disabilities that 
impact activity levels for some. 
 
Leveraging from prior experiences and successes of using ReCell within burn patients, 
this model will be the first to explore and allow for treating massive soft tissue injuries 
in a true traumatic setting. The results of the study will be presented at national 
meetings geared toward audiences that provide care to similarly injured individuals. 
 
5.PLAN 
5.1 Study Design 
This is a prospective, single-center, randomized within-patient controlled feasibility 
study to evaluate safety, tolerability, preliminary and long-term effectiveness of the 
ReCell device when used in combination with STSG mesh for healing of full-
thickness wounds previously treated successfully with INTEGRA™ MBWM. Due to 
the nature of the study, only patients whose wounds have been treated with 
INTEGRA MBWM as part of their standard of care will qualify for study 
participation. The local standard of care is considered the application of INTEGRA 
MBWM after the wound is amenable. Amenable being no evidence of evolving 
necrosis, clean and devoid of infection.  The INTEGRA is allowed to mature until it 
takes (adheres) to the underlying tissue, which takes 2 to 4 weeks until the wound is 
amenable for split thickness skin grafting.  Therefore, before consenting and 
enrollment into the study, the wound area to be studied will be treated first with 
INTEGRA™ MBWM then be allowed to heal for approximately two to four weeks 
(consistent with standard of care), at which time an assessment will be made to 

 
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determine if a viable granulation layer suitable for second stage grafting is present. 
(Note: At this time the patient will complete the consent process as described below 
in Section 5.5.2). 
 
The basic study design has the following characteristics: 
 
• 
Each subject will serve as his/her own control 
 
• 
After INTEGRA™ MBWM treatment (and once viable granulation is 
present), the study wound area will be divided into two regions within itself. 
Study treatment to each of the two regions will be assigned by 
randomization. Subjects will be blinded to treatment area assignments to 
avoid bias 
• 
Each subject will be treated with meshed STSG over both the control and 
ReCell regions of the Integra-treated wound.  The control area will have 
standard 1:1.5 meshing (only) STSG, and the experimental area will have 1:5 
meshing STSG plus application of ReCell (ReCell will be applied over the 1:5 
meshed STSG).  
 
Once harvested, a STSG may be meshed by placing the graft on a carrier and passing it 
through a meshing device. A skin graft may be meshed to provide coverage of a greater 
surface area at the recipient site, with expansion ratios generally ranging from 1:1 to 6:1. 
This also allows for expansion of the donor skin to be grafted/transferred and permits 
egress of serous or sanguineous fluid from under the graft; however, it results in a pebbled 
appearance upon healing that may ultimately be of poorer cosmesis. 
The carrier has a grooved side that must be directed superiorly and upon which the graft 
should be laid out. This technique allows expansion of the graft surface area up to 9 
times the donor site surface area. Expansion slits allow wound fluid to escape through 
the graft rather than accumulating beneath the graft and preventing adherence. To create 
a meshed graft, a “mashing” apparatus (Zimmer, Padgett, and/or Bryan meshing 
systems) is used to put open spaces in the STSG in an organized fashion.  This expands 
the graft so it can cover a larger surface area. The difference in ratios determines the 
expansion of the skin graft. For example, a 1:1.5 ratio has open spaces that are one and a 
half as large as the skin and a 1:5 ratio has open spaces that are five times as large as the 
skin.  The larger the meshing ratio, the larger the surface area that can be covered by the 
graft.  
a.                                                                               b. 

 
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c.  
 
 
 
 
 
                                                                                         
 
                                                                          d. 
 
 
 
 
 
e. 
  
 
 
 
      
 
. 
a. Zimmer Dermatome utilize to harvest the split thickness skin graft.  The thickness 
and width of the harvested graft can be adjusted. 
b. Dermatome blade width to determine the width of the harvested graft. 
c. Harvested split thickness skin graft 
d. Graft mesher 
e. Recipient site grafted. 
 
Treatment Summary Table: 
 
ReCell Region (experimental) 
Control Region (standard of care) 
ReCell + 1:5 Meshed STSG 
1:1.5 Meshed STSG (no ReCell) 
INTEGRA™ MBWM 
INTEGRA™ MBWM 
Wound Bed 
Wound Bed 
 
Allocation of treatments (Recell vs Control) to the INTEGRA™ MBWM treated 
wound sites will be assigned at random using a computer generated randomization 
table assignment to the two defined wound regions. Wound regions will initially be 
labeled A region and B region by the surgeon, and then the subject assigned 
randomization envelope will be opened to determine which of the two treatments will 
be used at A region and which treatment will be used at B region. 
 

 
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The wound area to be followed in the study will be between 200cm2  and 640cm2. 
One ReCell kit is intended to treat up to 320cm2 (which will cover half of the total 
“maximum” 640cm2  wound area), allowing for comparison with a similar size control 
area of up to 320cm2 that is treated according to the standard of care. 
In all cases, the ReCell region may be up to 320cm2 in size, the upper limit of 
application area for one ReCell kit, with a similarly sized control region. If the wound 
is larger than the combined control and ReCell regions (over 640 cm2), areas outside 
the study regions will be designated non-study areas and treated according to the 
standard of care. Additionally, areas with incomplete granulation, defined as a 
contiguous vascularized granulation layer at the INTEGRA™ MBWM application 
site, will be excluded from the study wound area. 
 
The same primary and secondary dressings will be used on ReCell-treated areas, 
control areas and donor sites. Once the wounds are determined to be healed, standard 
local clinical practice will be followed. 
 
In order to evaluate improvements associated with use of ReCell, within-subject 
comparisons across a battery of measurements and evaluations will be made. These 
measurements are divided into three categories: 
• 
Safety and tolerability measures 
• 
Preliminary effectiveness (acute healing phase) 
• 
Long-term effectiveness 
 
5.2 Anticipated Requirements 
Study procedures will be performed at WRNMMC within the following areas: In a 
private room within the Orthopaedic Surgery and/or Plastic Surgery Service clinic 
(screening and most post-operative visits), WRNMMC laboratory, WRNMMC 
Radiology, WRNMMC Dermopathology, WRNMMC Biomedical Research 
Laboratory (BRL) (obtainment of liquid nitrogen), WRNMMC Peri-Operative 
Services and surgical ward (Note, as per standard of care for surgical procedure and 
recovery) and utilization of the WRNMMC Investigational Pharmacy Services and 
the WRNMMC Information Technology (IT) Services (CHCS, Essentris and 
AHLTA) for conducting medical record review. Study procedures being performed 
at/by non-WRNMMC include: The collective monitoring activities intended to assess 
the investigator’s compliance with the protocol, the signed agreement, IRB 
requirements, and applicable FDA regulations in an effort to ensure human subject 
protection will be performed by IMARC, Inc.  Under the supervision of Dr. Peter 
Rubin (Sponsor and holder of the IDE), study data will be housed at UPMC and the 
Center for Innovation in Restorative Medicine (CIRM) will serve as the data 
management center.  Dr. Rubin will maintain oversight regarding regulatory 
requirements and compliance of clinical data and data analysis.  In collaboration with 
Dr. Rubin, coded data will be shared with Glaser Consulting who will perform all 
statistical analysis of data. Examination of cellular properties of the biopsy tissue 
material obtained from each subject by a member of the study team to determine skin 
composition relative to normal skin will be sent to and processed by an outside 
laboratory facility, Annapath, Inc. They in turn will ship slides back to WRNMMC to 
be interpreted by WRNMMC’s dermatopathologist, Dr. Abel Jarell. 
 
 The study design consists of screening pre-treatment/baseline assessments, an acute 

 
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phase and a long term follow-up phase. The acute phase duration is 6 weeks 
subsequent to treatment with INTEGRA™ MBWM and post treatment with the ReCell 
device. Subjects will continue to be followed for up to 24 weeks to capture long-term 
outcomes. The total duration of the subject’s participation in this research study across 
all visits, including screening and follow-up surveillance is expected to be up to 26-28 
weeks. 
 
The time required to complete the research (including data analysis) 
Anticipated Start Date: May 2014 
Expected Completion Date: Oct 2017 
 
Budget and Source of Funds 
Please see Appendix K for copy of budget 
Funding will be provided by the United States Army Medical Research Acquisition 
Activity (USAMRAA) under Grant # W81XWH1320004 
 
5.3 Subject Population 
The research population to be studied will include male or female military healthcare 
beneficiary of any race or ethnicity, aged 18 years or older, who is being treated for a 
traumatic wound at WRNMMC.  With a target enrollment of 20 evaluable subjects, this 
investigation will include individuals treated for traumatic wounds at WRNMMC with 
full-thickness wounds, with loss of the dermis extending to deeper tissue layers and 
disrupting dermal blood vessels, and deep partial-thickness wounds, with injury limited 
to the epidermis and superficial dermis with no damage to the dermal blood vessels 
that were successfully treated with INTEGRA™ MBWM.  Successful INTEGRA™ 
MBWM engrafting is defined as the presence of a contiguous vascularized granulation 
layer. 
 
It is planned to enroll a sufficient number of subjects at WRNMMC in order to ensure a 
total number of 20 evaluable subjects.  Therefore, up to 30 subjects will be consented and 
enrolled then screened to achieve a maximum of 20 evaluable subjects. Subjects who do 
not receive treatment with the assigned study device (ReCell) will be considered non-
evaluable and therefore a screen failure for study participation. 
 
WRNMMC will be the coordinating center for this clinical trial and will be the only site to 
enroll subjects for participation. The University of Pittsburgh, UPMC Center for 
Innovation in Restorative Medicine (CIRM), under the direction of Dr. J. Peter Rubin will 
be the Sponsor of the IDE and will also function as the Data Coordinating Center (DCC) 
accountable for maintaining oversight of all data management activities to ensure quality 
and integrity with accurate reporting, interpretation and verification, and will ensure 
systems and procedures are in place for the protection and safeguarding of the 
confidentiality of all data records. 
 
It is anticipated the availability of the study population will be derived from the 
investigators’ clinical practices, individuals evaluated and/or referred by healthcare 
providers aware of the study within the WRNMMC Orthopaedic Surgery, Plastic 
Surgery and General Surgery Clinics. Additionally, study participants will be recruited 
by use of a posting on the research registry at www.clinicaltrials.gov. Those interested 

 
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in study participation will be instructed to contact a study team member. This study 
will not use any advertisements, flyers or brochures. 
 
5.4 Subject Inclusion and Exclusion Criteria 
a. Inclusion Criteria 
Subjects will be eligible for study participation if they meet all of the 
following criteria: 
 
• 
The subject is a male or female military healthcare beneficiary of any 
race or ethnicity, aged 18 years or older, who is being treated for a 
traumatic wound at WRNMMC 
• 
The subject has soft tissue loss resulting from a traumatic mechanism 
such as an explosive blast (i.e. motar, rocket, IED), high-velocity shells 
(i.e. missile), an avulsion injury, gunshot wound motor vehicle accident 
and/or burn secondary to blast  
• 
The subject’s full-thickness or deep partial-thickness traumatic wound 
injury has been treated with  INTEGRA™ MBWM as part of their 
standard of care 
• 
The wound area is at least 200 cm2 
• 
All areas of the study wound area are covered with INTEGRA™ MBWM 
and has fully engrafted – engrafting defined as the presence of a 
contiguous vascularized granulation layer indicated by the formation of a 
viable granulation layer (Note: there may be some areas of incomplete 
granulation at the INTEGRA™ MBWM application site, these areas will 
be excluded from the study wound area). 
• 
The subject will comply with protocol requirements 
• 
The subject will provide voluntary written informed consent and 
Health Insurance Portability and Accountability Act (HIPAA) 
authorization 
 
b. Exclusion Criteria 
Subjects will not be eligible for study participation if they meet any of the 
following criteria: 
 
• 
The subject is pregnant and/or lactating (self-reported) 
• 
The subject has evidence of the following lab value results: 
a. Hematocrit  ≤ 20% 
b. INR > 1.8 second 
c. Creatinine (serum) > 2.0 mg/dL 
d. Bilirubin Total (serum) within upper limit of normal (normal range  
0.3-1.9 md/dL 
                          e.   Liver function test (AST/ALT) greater than 2 times upper limit of   
                                normal as defined by the clinical laboratory defined normal ranges   
                          f.    Albumin (serum) < 2.0 g/dL 
                          g.   Platelets < 70 K/µL 
• 
The subject’s targeted traumatic wound injury is a craniofacial wound  

 
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• 
The subject’s targeted traumatic wound injury is on a weight-bearing surface 
• 
The subject’s targeted traumatic wound is a full-thickness burn injury with 
visible eschar present (Note: Subjects with a traumatic wound of a burn nature 
secondary to an explosive blast injury resulting in significant soft tissue loss 
will NOT be excluded) 
• 
The subject has active infection processes, that in the opinion of the 
investigator may compromise safety or study objectives 
• 
The subject is known to have a pre-existing condition that may interfere 
with wound healing, e.g. malignancy, diabetes or autoimmune disease, 
immunocompromised blood borne diseases, has AIDS, is HIV or 
Hepatitis-A positive, or currently has a severe dermatological disorder 
(e.g. severe psoriasis, epidermolysis bullosa, pyoderma gangrenosum) 
• 
The subject has other concurrent conditions that in the opinion 
of the investigator may compromise safety or study objectives 
• 
The subject has a known hypersensitivity to Trypsin and/or 
Compound Sodium Lactate for Irrigation (Hartmann’s) solution 
• 
The subject cannot be compliant with study procedures and that, in the 
investigator’s opinion, would interfere with the study objectives 
5.5 Study Methodology/Procedures 
 
5.5.1 Describe when, where and how the study subjects will be identified and 
recruited. Study participants will be recruited from a population of patients being treated 
for a traumatic wound at Walter Reed National Medical Center (WRNMMC).  In this 
investigation, patients whose full-thickness wounds have been treated with 
INTEGRA™ MBWM as part of their standard of care will be considered for 
potential participation when a viable granulation layer has formed to allow for 
second stage grafting (approximately 2 to 4 weeks after Integra treatment).   It is 
anticipated availability of the population to be studied will be derived from  
investigators’  clinical  practices,  individuals  evaluated and/or referred by healthcare 
providers aware of the study within the WRNMMC Orthopaedic Surgery, Plastic 
Surgery or General Surgery clinics and services. Additionally, study participants will 
be recruited by use of a posting on the research registry at www.clinicaltrials.gov.  Those 
interested in study participation will be instructed to contact a study team member to 
receive an explanation of the study purpose, requirements and risks. This study will 
not use any advertisements, flyers or brochures. 
 
5.5.2 Consent Process 
WRNMMC will be the only site to enroll subjects for study participation.  Informed 
consent/HIPAA authorization will be obtained in a private room within the 
Orthopaedic Surgery, Plastic Surgery, General Surgery service clinic or at the 
potential subject’s bedside if he/she is an in-patient, by a member of the research 
team after educating the subject on the study specifics to include: the nature of the 
research study, study design schema, the risks and benefits of participation, what 
will be expected of them should they choose to participate, their  rights as a  
research  subject, any cost and payments. The potential subject will be allowed 

 
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ample time to review all information, exchange information and to ask questions. 
Should the potential participant wish to take the consent and review it outside of 
the clinic setting or discuss with other family members or medical personnel, he/she 
will be able to leave the clinic to do so and return at a later date. 
 
After reviewing all components of an IRB-approved informed consent/HIPAA 
authorization document and all questions regarding study participation have been 
answered to the potential participant’s satisfaction, the study investigator or his 
designee will obtain written informed consent/HIPAA authorization prior to 
beginning any research activities. Written consent will be obtained and documented 
in accordance with the principles of Good Clinical Practice (GCP) and International 
Conference on Harmonisation (ICH).  Source documentation of the consenting 
process will include, but not limited to, confirmation of the participants willingness 
to participate in the study after having been informed of all aspects of the clinical 
trial that are relevant to the volunteer's decision to participate and that written 
informed consent was obtained prior to conducting any study specific procedures.  A 
copy of the signed informed consent/HIPAA authorization document will be 
provided to the subject for his/her records in order to provide continuing references 
for contacts and a copy will be placed in the subject’s research chart. It will be 
documented in the source record that the subject was given a copy of the signed and 
dated fully executed consent/HIPAA authorization document. 
 
The original signed consent document will be placed and maintained in the study site’s 
regulatory files. The subject will then be assigned a unique 3-digit study ID number 
that will be used throughout the study to code all protected health information (PHI). 
 
Additional protections are in place to minimize undue influence of DoD personnel. 
These additional protections include the following: 1) Officers will be not be in 
uniform (will be in scrub attire) when obtaining consent and no visible indication 
of rank; 2) Officers cannot influence the decision of their subordinates to participate 
in the research; 3) Officers and senior non-commissioned officers cannot be present 
at the time of recruitment into the research; 4) Officers and senior non- 
commissioned officers have a separate opportunity to participate in the research. 
 
No research related tests or procedures, including but not limited to the screening 
procedures or the review of medical records will be performed before the informed 
consent/HIPAA authorization form has been obtained. 
 
Efforts will be made to promote the subject's understanding of the consent. At all times, 
the use of explanatory terms that are in accordance with the subject's education level will 
be utilized; the information provided to the participant will be in language understandable 
to him/her. No subject should grant consent until questions have been answered to 
his/her satisfaction.  Additionally, after obtaining the subject's voluntary consent, the 
Investigator and members of the study team will be obligated to continue to provide 
information as the subject's needs, or the clinical situation, dictate. The subject should 
understand that the study product is an investigational device and is not licensed by the 
FDA for commercial use, but is permitted to be used in this clinical research study. 
Informed consent includes the principle that it is critical that the subject be informed 

 
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about the principal potential risks and benefits. This information will allow the subject to 
make a personal risk versus benefit decision and understand the following: 
• 
Participation is entirely voluntary, 
• 
Subjects may withdraw from participation at any time, 
• 
Refusal to participate involves no penalty, and 
• 
The individual is free to ask any questions that will allow him/her to 
understand the nature of the protocol 
 
If there are any modifications made to the original protocol that may be relevant to the 
subject's original consent (e.g. change in study procedures, new PI assigned, significant 
safety or new information becomes available about the study device), the consent 
document must be revised to reflect the changes to the protocol.  If a previously 
enrolled subject is directly affected by the change, the subject will receive a copy of the 
revised IRB approved informed consent document.  Subjects still participating in the 
study will be re-consented by repeating the process of reading, signing and dating the 
revised consent/HIPAA authorization form to acknowledge protocol changes. 
 
5.5.3 Compensation for Participation 
Participants will not be compensated for participating in this study.  Should the 
participant be injured as a direct result of participating in this study, they will be 
provided medical care, at no cost, for that injury. They will not receive any injury 
compensation, only medical care. 
 
5.5.4 Research Interventions 
NOTE: All activities and procedures described below are being performed solely for 
the purpose of research unless otherwise specifically denoted as standard of care. 
 
Participants recruited for study participation consideration will be derived from 
investigators’ clinical practices, individuals evaluated and/or referred by healthcare 
providers aware of the study within the WRNMMC Orthopaedic Surgery, Plastic 
Surgery or General Surgery clinics and services. Additionally, study participants will be 
recruited by use of a posting on the research registry at www.clinicaltrials.gov. Those 
interested in study participation will be instructed to contact a study team member. 
 
In this investigation, subjects whose full-thickness wounds have been treated with 
INTEGRA™ MBWM as part of their standard of care will qualify for participation. 
Approximately two to four weeks after the patient has undergone INTEGRA™ 
MBWM treatment, the wound will be assessed by a clinician to verify that the 
INTEGRA™ MBWM treated wound has produced a viable granulation layer 
suitable for meshed STSG and ReCell treatment. If there is incomplete take of the 
initial INTEGRA™ MBWM, an additional treatment with INTEGRA™ MBWM 
may be performed. The patient will be treated according to standard of care until a 
viable granulation layer is present (approximately two to four weeks). Standard 
clinical care for this type of wound injury includes treatment with negative pressure 
wound therapy (NPWT) such as a wound vac device over the INTEGRA™ 
MBWM.  Therefore, potential study participants will be allowed to continue 

 
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receiving NPWT up until the time of the STSG procedure. After two to four weeks 
of incorporation of the INTEGRA™ MBWM product, coverage of the new dermal 
regenerate will then be the next step in staged reconstruction of these wounds. 
Assuming a viable granulation layer is present, the patient may be approached by an 
Investigator for their consent to participate. 
 
Following discussion of the protocol, including a thorough explanation of the 
experimental procedures, written informed consent and Health Insurance Portability 
and Accountability Act (HIPAA) authorization will be obtained from all subjects 
prior to performing any study-related tests or procedures. The subject will then be 
enrolled into the study and assigned a unique 3-digit study ID number that will be 
used throughout the study to code all protected health information (PHI). The 
investigator will maintain a Subject Enrollment Log for all participants consented 
and enrolled into the study.  The master Subject Enrollment Log will be kept in the 
study regulatory files in a locked file cabinet located in the Orthopaedic Surgery 
Clinic at WRNMMC. 
 
After the subject has been consented, he/she will undergo thorough screening 
procedures to assess eligibility to participate in the study. The specific screening 
procedures are outlined below. 
 
Screening Pre-Treatment/Baseline Assessments: 
Screening procedures will be performed by an investigator (PI and/or AI) up to 30 days 
prior to receiving treatment with the investigational device. 
 
A member of the study team will obtain a medical history including current medication 
use and allergies derived from both subject reporting and information obtained from a 
review of their medical record with a focus on pre-existing conditions that may interfere 
with wound healing. The surgical report from the INTEGRA™ MBWM treatment 
procedure will be included as part of the medical history and relevant data will be 
captured on the Baseline Medical History eCRF.  Demographic information (date of 
birth, gender, race/ethnicity) will be recorded on the eCRF. 
 
As part of the inclusion eligibility criteria, the subject will undergo a physical 
examination to include obtainment of the subject’s height, weight, temperature and vital 
signs (heart rate, respiratory rate and blood pressure).  Findings will be recorded on the 
eCRF. Any conditions or symptoms reported after the subject receives investigational 
product will be recorded as an adverse event (AE) on the AE eCRF.  This includes new 
events after study device administration, conditions that become more severe or increase 
in frequency, any disease-related signs or symptoms present at the Screening Pre- 
Treatment visit that have worsen in severity or frequency, as well as any event or finding 
that the Investigator feels is clinically significant. 
 
An evaluation of the traumatic wound area treated with INTEGRA™ MBWM will be 
made and recorded on the eCRF.  The total wound area will be measured. The wound 
area will be inspected to ensure all areas of the study wound has fully engrafted as 
indicated by the formation of a viable granulation layer as this will allow for grafting. 
Both of these findings will be recorded on the eCRF. 

 
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A baseline assessment for heterotopic ossification will be established using radiographic 
imaging.  Anterior/posterior and lateral films of the wound area targeted for treatment 
will be obtained. If the subject’s medical record contains an x-ray taken of the wound area 
targeted for treatment within 30 days prior to enrollment indicating the presence or 
absence of heterotopic ossification, these radiograph images (x-rays) may be used to 
avoid unnecessary exposure to radiation. 
 
A baseline assessment for pain and pruritus at the traumatic wound site will be obtained 
for comparison after receiving study treatment with ReCell. Subjects will be asked to 
rate their pain using a 0-10 point verbal numerical rating scale where “0” equals no pain 
and “10” equals worst pain possible. Additionally, the subject will be questioned if 
experiencing pruritus at the targeted wound site. If so, he/she will be asked to rate the 
intensity using the following options: mild, moderate and severe. Responses from both 
assessments will be recorded on the eCRF. 
 
A blood sample (15 mls) will be drawn for hematological analysis including a complete 
blood count (CBC) with differential panel, coagulation studies to include prothrombin 
time (PT) and international normalized ratio (INR) and comprehensive metabolic panel 
(CMP). Results will be reviewed by a physician investigator and documented on the 
eCRF. 
 
The total time of participant commitment for this portion of the screening pre-treatment 
baseline assessments including the consenting process will take approximately 1.5 to 2 
hours. 
 
Each subject must meet all inclusion and no exclusion criteria in order to qualify for 
receiving treatment using the ReCell device.  The PI or designee will make the final 
determination of subject eligibility. Subjects who sign the informed consent/HIPAA 
authorization document, but do not meet eligibility criteria will be defined as a screen 
failure. The investigator will maintain a screening log that documents the subject ID 
number and reason(s) for screen failure. 
 
Once the surgery plan has been determined, the following procedures will occur as part 
of standard of care: 
 
Scheduling Surgery 
An OR scheduler will select the first appropriate date and time for surgery according to 
OR time availability. 
 
Scheduling Pre-Operative Clinic Visit 
It is anticipated many of the subjects enrolled will be of an in-patient status. If not, the 
subject will be scheduled for a Pre-Operative clinic visit when the surgery date has been 
determined.  The subject will be informed he/she will be required to undergo a pre- 
operative evaluation to ensure suitability for surgery as per standard of care. Per 
WRNMMC procedures and guidelines for pre-operative patients, individuals will 
undergo the following activities prior to surgery: obtainment of a medical history 
including current medication use, a physical examination, weight, vital signs (heart rate, 

 
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breathing rate, and blood pressure), temperature, laboratory work and possibly, a standard 
chest x-ray and electrocardiogram (EKG), if deemed necessary. All females will be 
required to provide a urine sample for the purpose of pregnancy testing that must be 
negative in order to participate in this study as pregnancy is an exclusion criterion. No 
data will be collected for the pre-operative procedures performed. 
 
The total time of participant commitment for completing the Pre-Operative assessments 
will take approximately 1.5 to 2 hours. 
 
Upon confirmation of the subject’s eligibility and scheduled surgery date, an order for the 
ReCell kit will be written by the Investigator and sent to the WRNMMC investigational 
pharmacy to request the treatment ReCell device kit for availability on the scheduled day 
of surgery for the subject enrolled. 
 
The manufacturer of the ReCell Autologous Cell Harvesting Device, Avita Medical 
Americas, LLC, will supply the study site with ReCell kits containing the processing unit 
and items for cell harvesting. Arrangements will be made to have the investigational 
device kits shipped from the manufacturer directly to the Investigational Pharmacy 
Services at WRNMMC, to the ATTN: Dr. Parvenah Moussavian, Departmental Chief, 
where they will be housed until ordered by the investigator for use. 
 
Please refer to Section 5.6.2 for IDENTIFICATION AND DESCRIPTION OF 
INVESTIGATIONAL PRODUCT 
 
A Pharmacy Manual will be provided by the Sponsor to maintain records of 
investigational device disposition.  The Research Pharmacist will follow the procedures 
in this manual for maintaining adequate records for documentation purposes of shipment 
and receipt of the investigational device, device dispensing records and maintaining 
device accountability log and final disposition of the investigational devices to include 
return of unused devices. 
 
The ReCell device will be administered only to those subjects enrolled in the clinical 
study and under investigator or designee’s supervision (as noted on the 
Enrollment/Randomization Log and Delegation of Responsibility Log maintained in the 
study regulatory files). 
 
Re-verification of subject meeting all inclusion and exclusion criteria will be confirmed 
by the investigator before obtaining the ReCell device kit from the investigational 
pharmacy on the day of surgery. 
 
Treatments with the ReCell device will be staggered for the initial three subjects.  A 
treatment pause period of 1 week (5-7 days) will be implemented for the first and second 
subject, as well as the second and third subject within this study. 
 
On the day of surgery, a member of the study team will pick up 2 kits; one will be 
dispensed for use and the other will be obtained for the purpose of having “on-hand” in 
the event of a device malfunction while in the operating room. The investigational 
pharmacist will record dispensing of both device kits. One kit will be denoted as 

 
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“intended for use” and the second kit will be denoted as the “back-up device” in the 
device accountability log.  At the end of surgery, the second device deemed as the “back 
up device” will be returned to the investigational pharmacy by the study coordinator and 
logged back in on the device accountability log to be dispensed for future use with the 
next subject enrolled. Stringent record keeping of this process will be maintained for 
device accountability. 
 
Anesthesia procedures will follow the same clinical standards as all operative procedures 
performed at WRNMMC. Subjects will be maintained NPO after midnight the morning 
of surgery. With the ReCell treatment, the subject will be given general anesthesia during 
the entire procedure. No data will be collected for the anesthetic regimen provided. 
 
Surgical Procedure and Methods: 
Subjects will be anesthetized and the wound will be prepared according to hospital 
standard of care practices. It is anticipated that the total surgical time will be up to 3 
hours. The operative procedure will be performed by the PI and/or the Co-PI in the 
operating room at WRNMMC.  The INTEGRA™ MBWM treated wound will be 
sectioned into two similarly sized study regions up to 320cm2 each, the upper limit of 
application area for one ReCell kit. The surgeon will label these two regions “A” and “B” 
with a surgical pen. A pre-generated randomization envelope will then be opened to 
determine which area will be the control area and which area will be treated with ReCell. 
Any wound area outside the study regions will be treated according to standard of care. 
 
In this study, serial histology assessments of the wound site will be made. Baseline 
punch biopsies of 3 mm diameter tissue samples from the INTEGRA™ MBWM treated 
wound site and adjacent normal skin will be obtained in the operating room prior to start 
of the surgical procedure. This baseline histological analysis will examine the 
vasculogenesis and cytology of the regenerate before ReCell treatment.  The biopsy 
procedure will be recorded in the eCRF. 
 
A digital photograph will be taken of the control and ReCell sites (“A” region and “B” 
region) and noted on the eCRF. Next, the wound bed will be gently scrubbed and 
“prepared” then the thin silicone layer is removed, the wound bed will be prepped and 
prepared again for receipt of proposed STSG or STSG in conjunction with ReCell 
regenerative skin treatment system. 
 
Harvesting of autograft will be the same thickness for both control and investigational site; 
at a depth of 0.012 inch to 0.016 inch which is alignment with standard of care practice. 
Donor tissue for the STSG for the ReCell treatment area may be harvested from the same 
area as for the control STSG or separate area.  To assess healing of the donor sites for 
ReCell, the site has to be at a discrete location, but can be collocated, i.e. same thigh, but 
different area. 
 
A digital photograph will be taken of donor sites following tissue removal and will be 
noted in the eCRF. These and all subsequent photographs at each study visit will be 
taken in ambient light, with a consistent background and distance between camera and 
subject. 
 

 
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Donor tissue for the control assigned area will be meshed at 1:1.5 with a meshing system 
of the surgeon’s choice as per standard of care surgical practice. Application of the 
prepared STSG meshed at 1:1.5 will be secured in place with staples to the randomized 
control region.  
 
Donor tissue for the ReCell treatment assigned area will have a 1:5 meshed STSG using the 
same meshing system as the control area.  Application of the prepared STSG meshed at 1:5 
will be secured in place with staples to the randomized investigational region followed by 
the use of the ReCell device treatment over this widened STSG mesh as outlined below. 
 
ReCell 
Below is a picture of the investigational product, the Autologous Cell Harvesting Device 
kit (ReCell): 
 
 
 
The ReCell assigned area will be treated as described in the ReCell Instructions For Use 
(IFU) document and the “Set Up Card” included with each ReCell device kit (see 
Appendix A1 and 2). 
 
A representative from Avita Medical Americas, LLC will provide training to the PI and 
study team members for use of the ReCell device kit.  Initial training will be conducted at 
the site initiation visit.  Training will include review of the Instructions for Use (IFU) 
brochure which contains background and product safety information pertaining to the 
autologous cell harvesting device kit, materials and instruments needed during the ReCell 
procedure, step-by-step instructions for preparation and set up of the ReCell kit prior to 
use, ReCell skin processing, cell suspension preparation and cell suspension 
administration to the targeted ReCell wound region, aftercare and troubleshooting tips. 
 
Subsequent, periodic training on the investigational product over course of study will be 
carried out by the Avita representative and/or PI as needed (i.e. addition of new study 
team members). All training sessions for study personnel will be documented on the 
Study Personnel Training Log and will be placed in the study regulatory files. 
 
ReCell Procedure: 

 
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           1                      2                      3                     4                    5 
 
 
         6 
     
1. A thin, split thickness shave biopsy, 0.15 - 0.2 mm in depth, is taken of site matched skin 
2. Skin sample is incubated in the ReCell enzyme solution for approximately 15 minutes 
3. Skin sample is removed from incubator, mechanically agitated to separate cells 
4. Cells are then rinsed and collected using ReCell buffer solution 
5. Cells are filtered and suspension is drawn up 
6. ReCell suspension is then sprayed or dripped on wound followed by covering with recommended 
dressing  
 
The surgeon will follow manufacturer instructions for determining the appropriate skin 
biopsy size to cover the ReCell treatment area.  The ReCell donor site will be 
approximately 2cm x 2cm in area and harvested using a dermatone instrument of 
surgeon’s choice set at a depth of 0.006 inch to 0.008 inch (equivalent to 0.15 - 0.2 mm) 
(Note: the thickness for traditional skin grafts are thicker at a depth of 0.012 inch to 
0.016 inch).  Selection of a site-specific donor site is important for promotion of the 
same functional and cosmetic characteristics as the area to be treated with ReCell; e.g., a 
donor site is chosen with similar pigment and texture to the treatment site. Site-specific 
characteristics may include the thickness of keratinocyte layers in glabrous tissues (soles 
of the feet and palms of the hands), melanocyte distribution and secretory functions of 
the epithelium.  It is essential the donor site is clean, of appropriate depth, and shows no 
evidence of surrounding cellulitis or infection. Biopsy size, location and depth will be 
recorded in the eCRF. 
 
For optimum cell viability, the skin sample should be processed immediately after 
harvesting.  If a skin sample is harvested and processed according to the IFU, it should 
only require between 15 and 30 minutes of contact with the enzyme. The total time of 
incubation in enzyme solution will be recorded on the eCRF. Contact in excess of 60 
minutes is not recommended by the manufacturer; if this should occur, a protocol 
deviation will be reported to the IRB and Medical Research Monitor. 
 
The volume of suspension prepared is dictated by the size of the treatment area as 
identified in the ReCell IFU as indicated in the table below. The volume of cell 
suspension produced will be recorded on the eCRF. 
 

 
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Treatment Area 
200 cm2 - 260 cm2 
>261 cm2 – 320 cm2 
Buffer Solution Volume 
3 mL 
4.5 mL 
  
The cell suspension spray created using the ReCell device will be applied over the 
prepared STSG wound site meshed at 1:5 as detailed below.  The PI and/or Co-PI (only) 
will apply the investigational product to the pre-determined wound region. 
 
• 
For wound areas 200cm2 - 260cm2: The 18 gauge blunt cannula supplied with the 
ReCell device will be attached to the syringe containing the cell suspension. The 
syringe will be inverted several times prior to application to ensure an even 
suspension. Telfa™ Clear wound dressing (Covidien, USA) will be applied to the 
inferior margin of the wound and the cell suspension will be manually dripped 
along the superior edge of the wound. 
 
• 
For wound areas >261cm2 - 320cm2: Telfa™ Clear wound dressing (Covidien, 
USA) will be applied to the inferior margin of the wound. The spray nozzle 
supplied with the ReCell device kit will be attached to the syringe containing the 
cell suspension using firm pressure. The syringe will be inverted several times 
prior to application to ensure an even suspension. The spray applicator will be 
held approximately 10 cm from the most elevated point of the wound surface and 
moderate pressure will be applied to the plunger of the syringe. Spraying begins at 
the most elevated part of the wound so that any run-off helps to cover the more 
dependent areas of the wound. One application of a fine mist of cells will be 
delivered to the entire wound surface. To cover the area, the spray applicator will 
be carefully moved in one continuous motion from one side of the wound to the 
other while spraying. Special care will be taken by the surgeon when applying the 
ReCell spray to ensure the cell suspension is only applied to the designated 
treatment area; the dressing will serve as a barrier to avoid applying the spray skin 
to the control area.   
 
The volume of cell suspension applied to the ReCell treated wound and method of 
application will be recorded on the eCRF. 
 
The ReCell suspension will be applied to the designated randomized treatment region 
only; donor sites will not receive application of any Recell suspension.  Any deviations 
from this will be captured in the eCRF.  
 
The subject will not be made aware of treatment area assignments (will be blinded) until 
study participation completion to avoid bias when completing questionnaires provided at 
each follow-up visit. 
 
Dressings:  
  Upon completion of the surgical procedure, the treatment area and donor sites will be   
  dressed in the following manner: 
 
The primary dressing will be Telfa™ Clear wound dressing (Covidien, USA). Post- 
treatment photographs will be taken after placement of the primary dressing. After 

 
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placement of the primary dressing, a secondary dressing, Xeroform™ Petrolatum Gauze 
(Covidien, USA) will be applied to keep wounds moist then area will be wrapped with 
bulk dressing (e.g. gauze) to protect the wound surface, with or without an adhesive 
retention dressing as clinically indicated. The primary and secondary dressings should 
remain in situ for a minimum of 6 to 8 days and are not to be manipulated until the first 
post-operative visit unless medically necessary. 
 
The donor area will be dressed in the following manner: The primary dressing will be 
Xeroform™ Petrolatum Gauze (Covidien, USA). The area will then be wrapped with 
bulk dressing (e.g. gauze) plus or minus a compressive wrap (ace-wrap) based on the area 
of harvest (extremity vs torso).   The donor area bulk dressing will be removed at 48 
hours.   The primary dressing (Xeroform™ Petrolatum Gauze) will remain in place and 
be gradually peeled off over several days. 
 
The primary dressing can be trimmed and removed as the Telfa™ Clear lifts from the 
wound bed.  Under no circumstances will the primary dressing be forcibly removed; the 
Telfa™ Clear should be allowed to fall off on its own accord.  If the Telfa™ Clear 
dressing hasn’t fallen off in 3 weeks, only at this time point can it be moisten to peel off. 
It is essential that any dressing not easily removed be soaked in aqueous or oil-based 
solutions to prevent trauma upon removal.  Once the primary dressing has been removed, 
a dressing of the investigator’s choice will be applied to protect the wound surface, with 
or without an adhesive retention dressing as clinically indicated.  All dressing regimens, 
dressing changes and dressing types will be recorded on the eCRF. Once the wounds are 
determined to be healed, therapy will be applied that is consistent with the standard of 
care at the clinical site. 
 
Any dressing used other than Telfa™ Clear as primary dressing and Xeroform™ 
Petrolatum Gauze as secondary dressing at the treatment site areas prior to wound healing 
will be considered a protocol deviation. 
 
Negative pressure wound therapy (NPWT) (i.e. wound vac) will not be reapplied after 
treatment with ReCell as this may compromise the treated area by removing the applied 
cells. 
 
Post-Operative Care: 
Following surgery, subjects will be transferred to the Post Anesthesia Care Unit (PACU) 
and then to the In-Patient ward. Post-Operative recovery in terms of hospitalization and 
length of stay will be as per standard of care for this type of procedure. 
 
It has been identified from previous use, the loss of formed skin at the ReCell site appears 
to be primarily associated with secondary trauma due to inadvertent inadequate care 
and/or protection of the newly epithelialized area. As a corrective measure, the wound 
will be appropriately protected while the skin is maturing. These measures include use of 
appropriate protective dressings after initial wound closure to give the epithelium 
adequate time to mature and cornify, ensuring the primary dressing removal is atraumatic 
and not before post-treatment Day 6 and avoidance of potentially damaging cleansing 
regimens and cytotoxic creams (i.e., silver sulfadiazine). Additionally, for the duration of 
their care, subjects will be informed on the following post-treatment ReCell site care 

 
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guidelines recommended by the manufacturer: 
 
• 
Prevent the treated area from getting wet while the wound is still open 
 
• 
Refrain from strenuous activity 
 
• 
Protect the healed area; don’t bump, wear loose clothing over treated area 
 
• 
Once the area has healed, massage and keep area moisturized (using a gentle 
moisturizer) at least twice a day 
 
• 
Avoid direct sun exposure at least 4 weeks following treatment and use sunscreen 
 
Post-Treatment Study Visits 
Subjects will be re-evaluated by the Orthopaedic Surgery Service, General Surgery 
Service and/or Plastic Surgery Service clinic at WRNMMC or on the in-patient wards. 
At all post-treatment study visits (Week 1 ± 3 days, Weeks 2, 3, 4, 6 ± 2 days, Weeks 12 
and 24 ± 14 days post-treatment), the PI and/or AI will perform the following 
assessments as outlined below: 
 
• 
Wound and Donor Site Healing Assessments: The ReCell treated area and 
control site will be assessed by an Investigator for signs of atypical healing, 
including delayed healing (not healed 95% or greater by Week 6 post-treatment), 
inflammation, heterotopic ossification, scar contracture and graft loss. 
Inflammation in the absence of infection will be assessed as a possible allergic 
reaction to Trypsin (see below). Any signs of atypical healing will be detailed in 
the eCRF. Each of the donor sites will be assessed for signs of infection and 
healing (healed ≥ 95% or not healed by Week 4 post-treatment). Findings will 
be recorded on the eCRF. 
 
• 
Infection: The presence of infection for the ReCell treated areas and the control 
site will be evaluated at each postoperative visit. Infection will be evaluated in 
accordance with the Center for Disease Control (CDC) guidelines for nosocomial 
infections using standard clinical measures such as visual examination of the 
treatment sites for delayed healing, redness, inflammation and surrounding 
cellulitis. In the presence of symptoms (i.e., purulent exudate, changes in wound 
appearance such as hyperemia, and erythema in the uninjured skin surrounding 
the wound), infection will be confirmed using microbiological testing procedures 
and treatments initiated according to the institutions’ infection management 
protocols, which will be recorded on the eCRF. Infection will be managed 
according to the standard protocols of the clinical site. For example, treatment of 
infection will involve the daily cleaning and dressing of wound sites until such 
time that the infection is clear. Treatment with broad spectrum antibiotics until 
microbiology sensitivities return from the testing laboratory is recommended. 
Upon return of sensitivities, antibiotic therapy may either continue as is, or be 
changed at the discretion of the investigator. All treatment regimens applied in 
the management of infection will be recorded in the eCRF. 
 

 
Page 33 of 76 
Dermal Protocol Version 4, 04 SEP 15 
 
• 
Allergic response to Enzyme (Trypsin): The allergic response to Trypsin, the 
enzyme used in the ReCell Device for disaggregation of the biopsy, will be 
evaluated.  An allergic response to Trypsin is most likely to present as contact 
dermatitis (defined as an altered state of skin reaction induced by exposure to an 
external agent). Substances that produce this condition after single or multiple 
exposures may be irritating or allergic in nature and induce an inflammatory 
response.  The most common clinical expression of this induced inflammation is 
dermatitis (eczema). The evaluation tools for assessment of the allergic response 
to Trypsin have been developed in accordance with guidelines published in the 
Journal of the American Academy of Dermatology [Drake, LA, et al., 1995]. Any 
allergic response(s) to trypsin will be recorded in the eCRF and depending on 
severity, will have additional reporting to the IRB and Research Monitor. 
 
• 
Durability: Abrasions or injuries at the graft site due to graft fragility will be 
noted and described in the eCRF. 
 
• 
Digital Photography: The healing process at the ReCell donor site and at the 
treated and control wound sites will be documented pictorially. Photographs 
obtained will be documented in the eCRF. 
 
• 
Vital Signs: Vital to be assessed include oral temperature, heart rate, respiratory 
rate and blood pressure. Results will be recorded in the eCRF. 
 
• Subject complaint: Subject complaints will be rated on a 10-point scale by the 
subject utilizing the “patient” portion on the POSAS (see description below) for 
the treated wound sites and documented in the eCRF. 
 
• Adverse Events: The research team will assess if the subject has experienced 
any adverse effects post-treatment with the investigational device.  The subject 
will be asked if he/she has any problems, issues and/or concerns since the last 
encounter visit that could be potentially related to study participation. Other 
treatment-related adverse events requiring surgical intervention prior to Week 12 
post-treatment and all serious adverse event (SAE) occurrences will be treated 
and recorded in the eCRF.  For all adverse events, the Investigator will provide 
an assessment of the event, its treatment resolution, and relationship to the 
investigational device. 
 
• 
Concomitant Medication Use: Concomitant medication use (excluding 
anesthetic regimen) and all treatment regimens applied in the management of 
infection during the acute healing phase will be recorded in the eCRF. 
Concomitant medication used for the treatment of an adverse event occurring 
from time of receiving investigational product through Week 24 post-treatment 
will also be recorded in the eCRF 
 
In additional to above assessments, additional “visit specific” assessments will be made 
as outlined below: 
 
At Week 1 post–treatment: 

 
Page 34 of 76 
Dermal Protocol Version 4, 04 SEP 15 
 
 
• 
Bloodwork: A blood sample (15 mls) will be drawn for hematological analysis 
including a complete blood count (CBC) with differential panel, coagulation 
studies to include prothrombin time (PT) and international normalized ratio 
(INR) and comprehensive metabolic panel (CMP), which is consistent with 
standard of care practices.  The sample will be labeled and processed by 
WRNMMC laboratory medicine per institutional policy.  Due to the nature of 
complexity and multi- system involvement resulting from trauma in the targeted 
subject population, the occurrence of a deviation from the institutional normal 
reference range(s) for laboratory assay results is anticipated.  Therefore, 
laboratory levels falling outside of the “normal” reference range and/or with a 
change in test result of 20% from baseline value will be evaluated for clinical 
significance by the Principal Investigator and/or AI physician.  Any laboratory 
value deemed clinically significant will be captured on the adverse event eCRF. 
Additional laboratory testing will be performed only as clinically indicated. 
 
At Week 2, 4 and 12 post–treatment: 
 
• 
Histology: 3-mm punch biopsies will be obtained by a physician investigator. A 
sample collection of 3mm diameter will be taken from both the control and 
ReCell treated sites and documented in the eCRF.  Biopsies will be obtained 
from a centralized region of each wound. Biopsies will be taken for histologic 
analysis and analyzed to determine skin composition relative to normal skin. 
 
At Week 12 and 24 post-treatment: 
 
• 
Scar Assessment Scales: The entire POSAS (both patient and observer scales) 
will be utilized (see Appendix B).  Scar appearance will be assessed by the patient 
and by two independent observers (WRNMMC dermatologist subject matter 
expert investigator) who will be blinded to treatment provided at the wound site.  
Each scar (control and ReCell-treated sites, denoted on assessment forms as A 
Region and B Region due to “blinded” component) will be evaluated once by 
each observer.  The evaluations will be made blind to each other. Findings will be 
documented in the eCRF. 
 
In addition, the Vancouver Scar Scale (VSS) (see Appendix C) will be used at 
each of these visits. Using word descriptions, the VSS assesses four variables: 
scores pigmentation, vascularity, pliability and scar height/thickness. The four 
categories are given a score between 0 and 3 or 0 and 5, depending on the value, 
leading to a total score between 0 and 13 points.  Evaluations of the control and 
ReCell-treated sites (denoted on assessment forms as A Region and B Region due 
to “blinded to treatment” component) will be performed utilizing this scale by the  
two independent observers (WRNMMC dermatologist subject matter expert 
investigator)  who will be blinded to treatment provided at the wound site and 
will be recorded in the eCRF. 
 
• 
Functional Outcome Rating Questionnaire: The Functional Outcome Rating 
Questionnaire consists of a 10-point visual analog scale (see Appendix D) used to 

 
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Dermal Protocol Version 4, 04 SEP 15 
 
rate scar pain.  Subjects will be asked to evaluate the amount of scar pain 
experienced at the control and ReCell-treated sites (denoted on assessment forms 
as A Region and B Region due to the subject being “blinded” to treatment). 
Findings will be documented in the eCRF. 
 
• 
Patient Satisfaction: A 2-question (per study area) non-standardized Patient 
Satisfaction Questionnaire regarding treatment (denoted on assessment forms 
as A Region and B Region due to “blinded to treatment” component)  (see 
Appendix E) will be completed by the subject and documented in the eCRF. 
 
At Week 24 post-treatment: 
 
• Radiographic imaging (anterior/posterior and lateral films) for assessment of 
presence/absence of heterotopic ossification.  
 
The total duration of participant time commitment for each of the post-treatment study 
visits is approximately 1 hour. 
 
Subject Discontinuation and/or Withdrawal 
A subject may withdraw consent and discontinue participation in the study at any time and 
for any reason without penalty, if he/she wishes to do so. The investigator may also 
withdraw a subject if continuing participation is believed to be harmful to the subject’s 
well-being or in the event of protocol violations, non-compliance (i.e. loss to follow-up), 
the need to initiate care contraindicated to study procedures and/or requirements, 
pregnancy, serious inter-current illness and if the study is cancelled due to other 
administrative reasons and/or unanticipated circumstances by the Sponsor of this study or 
the FDA. Additionally, the subject’s participation may be stopped without their consent if 
the military mission requires it or if the individual loses his/her DoD healthcare 
beneficiary status. 
 
If the subject’s participation is stopped, the investigator will notify the subject and 
provide reason for doing so in person, by mail, email and/or telephone. 
 
In the event that the subject withdraws and/or is withdrawn from the study before the 
completion of the Week 24 post-treatment assessment, he/she will be asked to come to 
the clinic for a final assessment of safety evaluations. If a subject withdraws before 
study completion, the reason for discontinuation will be captured on the appropriate 
eCRF page. Additionally, any data collected up until the time of subject withdrawal will 
be included in the final study analysis. (Please see section 5.5.7 for additional 
information pertaining to biological specimens/withdrawal) 
 
Subjects who are withdrawn will not be replaced if they have received study treatment. 
 
Additional Information: 
Patient and Observer Scar Assessment Scale (POSAS) 
The standard and comprehensive Patient and Observer Scar Assessment Scale (POSAS) 
[Draaijers LJ, et al., 2004] will be employed in this study, as a standard tool for capturing 
both the subject’s and two independent observer’s assessment of the scar post-treatment 

 
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Dermal Protocol Version 4, 04 SEP 15 
 
[Idriss N, 2009]. Although many methods of rating scars exist, little consensus exists to 
dictate which method is optimal [Fearmonti R, et al., 2010, Durani P, et al., 2009]. 
Objective measures may be useful for evaluating a particular characteristic (e.g. color or 
elasticity), but these do not satisfactorily convey overall, clinically-relevant information 
about the scar as a whole [Brusselaers N, et al., 2010]. 
 
The POSAS, consists of two multi-item numeric rating scales, an observer scale and a 
patient scale. The Observer Scale is devised with items based on literature review and the 
authors’ clinical experience: ‘vascularization’, ‘pigmentation’, ‘thickness’, ‘relief’, 
‘pliability’ and ‘vascularization’ rated on a 1 - 10-point numeric scale, with ‘normal skin’ 
and ‘worst scar imaginable’ used as end-anchor labels. The items on the Patient scale 
directly correspond to these except with regard to scar color. Individual items for both 
scales are summed with higher scores representing poorer scars and lower scores 
representing scars more closely resembling normal skin. Both scales have demonstrated 
acceptable internal consistency (Cronbach’s alpha 0.76 (patient) and 0.69 (observer 
scale)), suggesting that individual items for each scale can be reliably summed to 
generate a total score. The POSAS has the added benefit of capturing the subjects’ ratings 
for scar pain and itching and expands on the objective data captured in the VSS. 
 
Vancouver Scar Scale (VSS) 
The VSS is a quantitative objective scale which seeks to provide a standard for analyzing 
scar tissue. This assessment tool is widely used in clinical practice and research as it 
allows for a means to document changes in scar appearance. The scale is based on four 
values: pliability, height, vascularity and pigmentation. The four categories are given a 
score between 0 and 3 or 0 and 5, depending on the value, leading to a total score 
between 0 and 13 points. A low score indicates an appearance closer to normal skin. 
 
Malfunction of ReCell Device 
In the event of a malfunction occurrence of the ReCell device or any of the kit 
components, the “back-up” ReCell device dispensed by the investigational pharmacy will 
be utilized.  In addition, if a ReCell kit or any of its components malfunctions and is 
replaced or results in an adverse event occurrence, the information will be documented in 
source documents and captured in the eCRF. 
 
Procedure If Malfunctioning of Investigational Device Occurs: 
If any device fails to operate, the failed ReCell device (kit) system will be returned to 
Avita Medical for evaluation via use of their established Return Material Authorization 
(RMA) process.  Per manufacturer directives, the study site will notify manufacturer of 
need to return malfunctioning investigational device kit. They in turn will generate and 
send site an Investigational Device Return Form along with a return FedEx air bill to 
cover return shipment fees. The devices will be returned to the address below: 
 
Return to: 
Avita Medical 
c/o Parker Hannifin Corp 
ATTN: Customer Service 
3007 Bunsen Avenue, Suite L 
Ventura CA 93003 

 
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Dermal Protocol Version 4, 04 SEP 15 
 
Telephone: 818) 356-9419 
 
Histological methods: 
Histological methods will be similar to those used in the Moiemen and colleagues article 
[2006] who described histological analysis of punch biopsies taken from patients who 
had received INTEGRA™ MBWM treatment. That study identified four stages of tissue 
development after application of Integra. The first three phases, imbibition, fibroblast 
migration and neovascularization should be well established by the proposed study’s first 
histological assessment four to six weeks after INTEGRA™ MBWM application (two 
weeks after ReCell treatment).  Histological assessment of the proposed study will 
therefore focus on the last phase, remodeling and maturation, which begins four weeks 
after INTEGRA™ MBWM application, coinciding in time with our first scheduled punch 
biopsy. During this remodeling and maturation phase, fibroblasts imbue the matrix and 
fill the interstices with host collagen. Matrix collagen is progressively replaced by this 
new host collagen which appears as normal dermis. The neodermis is initially thicker 
than normal dermis, but becomes thinner and more pliable as it matures over a period of 
months.  In the Moiemen study, an autograft was applied to the wound four weeks after 
INTEGRA™ MBWM treatment. The autograft was seen to adhere to the surface of the 
neodermis during this final phase, and rete ridges were seen along the dermal-epidermal 
junction. Given the similarities between the proposed study and the methods used by 
Moiemen and colleagues, we expect both ReCell-treated and control areas will show 
histological similarities to the results seen during the remodeling and maturation phase 
described in that study. 
 
Punch biopsies of 3mm diameter will be obtained pre-skin graft from /the INTEGRA™ 
MBWM treated wound site and adjacent normal skin and from ReCell and control 
treated sites at Weeks 2, 4 and 12 post ReCell treatment. The investigator will discuss the 
procedure with the subject in detail and will obtain a separate consent form as per 
standard of care.  Samples will be analyzed to confirm the thickness of new tissue and 
assess the normality of structures present in the newly regenerated skin. 
 
With the exception of the baseline INTEGRA™ MBWM treated wound site and adjacent 
normal skin punch biopsies, the procedure will take place in a private room within the 
Orthopaedic Surgery, General Surgery Service and/or Plastic Surgery Service clinic at 
WRNMMC. Utilizing sterile technique, the site will be prepped and draped as per 
standard of care. Approximately 3-5cc’s of 1% lidocaine (with epinephrine) solution will 
be instilled as a local analgesic to the treated wound area (Note: No local analgesic will 
be used for pre-STSG sample as subject will be anesthetized for surgical procedure).  
The specimen will be obtained by using a standard punch biopsy instrument consisting 
of a circular blade, which is rotated down through the epidermis and dermis, and into the 
subcutaneous fat. The PI and/or AI, who are surgeons, will collect a 3mm diameter 
cylindrical core of tissue sample from a centralized region of both the control and ReCell 
treated wound sites. 
 
All tissue samples will be coded and labeled with the subjects’ 3-digit ID number, date 
and time of harvest. Tissue samples will be cut in half with a sterile scalpel; one half of 
the sample will be preserved in 10% formalin by a member of the study team then 
delivered to Annapath Inc via courier pick-up for tissue processing, embedding (paraffin 

 
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blocks), microtomy and slide preparation as per Annapath, Inc Technical Guidelines and 
Annapath, Inc Procedure Protocol (see Appendix F and  Appendix G ). The other half 
of tissue sample will be flash frozen with liquid nitrogen then stored in a -80° freezer 
with alarm system located within the Department of Orthopaedics Biomedical Lab 
Room 2010, Building 19 (America). 
 
Following the methods detailed by Moiemen and colleagues, hematoxylin and eosin 
stains will be used to detect blood cells and adnexal structures, vimentin stain will be 
used to detect esenchyme-derived cellular elements including fibroblasts, and S100 will 
be used to stain neuroectodermal tissue. Vascularization will be assessed by 
immunohistochemical analysis using antisera to endothelial cell markers CD31 and 
CD34.  In addition, Verhoeff-Van Gieson (VVG) stain will be used for identifying elastic 
fibers and Masson’s Trichrome stain will be used for the detection of collagen fibers. 
 
Sections will also be assessed visually with an electron microscope to aid morphological 
evaluation of structures by WRNMMC’s dermatopathologist.  The dermatopathologist 
will provide a written report summarizing their findings. This information will be 
captured in the eCRF and entered into the database. 
 
The Research Coordinator will call the subject within 72 hours after the biopsy procedure 
to obtain a subject self-report assessment of signs/symptoms of an adverse event post- 
biopsy (bleeding or signs/symptoms of infection) as standard of care follow-up to a 
surgical procedure. 
 
Digital Photography Method: 
When followed by different physicians, a uniform assessment of changes in the healing 
process needs to be established.  Therefore, to facilitate uniform assessment/rating and 
improve reproducibility of the results, digital photography for clinical evaluation and 
follow-up of subjects will be utilized to minimize variations between different assessors.  
The definition for successful healing of the target wound via digital photography will be 
defined as: The target wound will be deemed as “successful healing” when 95% or 
greater re-epithelialization is noted upon visualization of the treated wound within the 
photograph taken. 
 
In this study, clinical photographs will be obtained through the Biomedical Photography 
Department located at WRNMMC. 
 
The Biomedical Photography Department is responsible for all medical photography 
taken and stored at WRNMMC. Photos taken through Biomedical Photography 
Department are obtained as standard of care and are stored and maintained as a part 
of the patient’s medical record following institutional policies. Digital photographs 
will be taken in ambient light with a consistent background and distance between 
camera and subject.  Physical features identifying the subject (i.e. tattoo or 
birthmark), if present, will be hidden in photographs. 
 
A photograph of the wound will be taken pre-treatment and then serial photographs 
will be taken of the ReCell donor site and at the treated and control wound sites at 
each follow-up visit. Additional photographs may be obtained outside of the 

 
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stated study time points for evaluation purposes if medically indicated (i.e. 
incomplete healing and/or AE occurrence). 
 
A copy of the digital photographs will be obtained from the Biomedical Photography 
Department to be placed in the study files. Photographs will be coded by using the 
unique 3-digit study ID number and labeled each with the date the photograph was 
obtained, the corresponding visit (e.g. pre-treatment and/or post-treatment week) and 
site location (e.g. treatment site (ReCell or control) or donor site (ReCell donor site 
or STSG) then placed on a disc to be stored with the main study database at 
completion of the study. 
 
5.5.5 Data Collection 
Data management activities and statistical analytical support will be performed by the 
UPMC Center for Innovation in Restorative Medicine (CIRM) and its consultant, Glaser 
Consultants. With oversight provided by J. Peter Rubin, MD, CIRM will prepare a Data 
Management Plan (see Appendix H) and serve as the Data Coordinating Center (DCC) 
for all data management activities.  The DCC will have no direct interaction or 
intervention with study subjects.  The DCC will manage design, implementation and 
maintenance of the database, data entry, editing, ongoing quality control of the data, 
generation of reports, staff training, interval database access for investigative personnel, 
back-up and data security.  
 
For this clinical trial, data will be collected at WRNMMC only then transcribed onto an 
electronic case report form (eCRF). No database is anticipated of data collected at 
WRNMMC; all data maintenance and analysis will occur only at CIRM. 
 
Subject data collected for this research project will be entered into the Medrio electronic 
data entry system via use of a web browser. Medrio is commercially available software 
that provides an integrated eClinical Software as a Service (SaaS) platform with a fully 
hosted Electronic Data Capture (EDC) system. The Medrio system is a secure, regulatory 
compliant, web-based, electronic data capture tool designed to support research studies 
that requires an individualized password protected login in order to have access to the 
application.  
 
The DCC/UPMC will secure the required educational license agreement (the University of 
Pittsburgh will serve as the educational institution of record) that is necessary, free of 
charge, for procurement of the Medrio system software tools to allow for database 
development.  The DCC/UPMC will have sole ownership of the database. No parts of the 
database will be downloaded to the DoD network or devices. 
 
Data will be collected from source documents and data collection forms designed in 
tandem with the protocol.  Key datasets derived from the study protocol (see Appendix 
L, Sample eCRF) will be mirrored for database development by the DCC.  
 
De-identified (coded) data collection entries into the Medrio system will occur on an ongoing 
basis during subject participation and will be performed by WRNMMC research team 
members only.  Subjects will not be entering study specific questionnaire responses into the 
data entry system; they will be asked to complete a paper version handout. 

 
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Working from source documents and the data collection forms, the Research Coordinator will 
update the Medrio data management system within one week after each scheduled study visit 
for the subject. 
  
All data collection activities will be monitored by IMARC Research, Inc.; qualified 
monitors, based on training and experience, will be assigned to this study as per Clinical 
Monitoring Plan (see Appendix I).  Periodic onsite monitoring visits will be made to 
WRNMMC by the IMARC Research, Inc. clinical trial monitors to inspect the conduct 
of the study to determine if it is being executed according to the protocol and report 
their findings to the Sponsor. The monitors will assure that data is accurately captured 
on the eCRF and in agreement with source documentation; verify that investigational 
product is properly stored and accounted for, verify that subjects’ consent for study 
participation has been properly obtained and documented, confirm that research 
subjects entered into the study meet inclusion and exclusion criteria, and assure that all 
essential documentation required by Good Clinical Practice (GCP) guidelines are 
appropriately filed.   
 
In collaboration with Glaser Consultants, CIRM will perform all statistical analysis of 
intermittent data and upon completion of all subject visits. 
 
The Investigator is responsible for maintaining any source documentation related to the 
study, including digital photographs of the donor sites and wound site treated with the 
investigational product, clinical laboratory data, radiographic imaging (x-ray results) for 
assessment of heterotopic ossification, histology analysis, informed consent forms and 
device accountability records. 
 
a.   Method of Collection from Study Participants: 
Please refer to above Section 5.5.4 
Please refer to CRF’s included with this submission 
 
The method for collection of clinical data from study participants by members of the 
study site personnel will be derived from interviews and assessments performed by the 
study investigator and/or coordinator during study visits. Study materials, information, 
photographs, radiographic imaging (x-ray results) for assessment of heterotopic 
ossification and biopsy samples obtained for the purpose of this clinical trial will be 
coded with the subjects assigned 3-digit study ID number.  Listed below is data that will 
be collected at the following time points: 
 
Screening/Pre-Treatment: Data collected will be information obtained from the 
subject’s medical history including current medication use, allergies, information 
related to the traumatic injury, treatment with INTEGRA™ MBWM, demographic 
information, physical examination including height, weight and vital signs, pre-
treatment photograph of treatment sites and donor sites, bloodwork for 
hematology/chemistry analysis, baseline pain and pruritus assessments at traumatic 
wound site using the POSAS tool, baseline radiographic imaging (x-ray results) for 
assessment of heterotopic ossification (if not previously obtained within 30 days of 
study enrollment), histological assessment and identification of randomized treatment 

 
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areas. 
 
Surgical Procedure: Data collected will be: Wounds dimensions, the ReCell device lot 
number and expiration date, lot numbers (from inner and outer package box) for the 
enzyme and expiration date, information regarding device kit preparation for ReCell 
suspension and application, intervention photographs before treatment and after tissue 
removal, initial wound dressings, biopsy procedure information, and any device 
and/or surgical related problems or concerns, if any. 
 
Acute Healing (Week 1, 2, 3, 4, and 6 post-treatment): Data collected will be 
atypical epithelialization (healing) characteristics at the wound and donor sites, 
wound dressing/treatment regimens, photography at the treatment and donor sites, 
biopsy for histology, scar pain/itching rating using the POSAS, results from routine 
laboratory tests obtained at Week 1 post-treatment, concomitant medication use 
and any adverse event occurrences; both subject reported and medical record 
review. 
 
Long-term Outcome (Week 12 and 24 post-treatment): Data collected will be atypical 
epithelialization (healing) characteristics at the wound and donor sites, photography at the 
treatment and donor sites, radiographic imaging (x-ray results) for assessment of 
heterotopic ossification, biopsy for histology, scar pain/itching rating using the full 
POSAS (both Subject and Observer), scar assessment using the Vancouver Scar Scale, 
functional outcome rating questionnaire, patient satisfaction questionnaire results and any 
adverse event occurrences; both subject reported and medical record review. 
 
b. Source and Type of Data Collected from Existing Data Sources: Answer the 
questions below after considering the minimum necessary data required for the 
research study. 
 
i. Have you received a data consultation with a data expert to determine the data 
elements to be extracted or the data system to access?  (Consulting with a data 
expert often saves time later in the compliance process because the data expert 
can advise on the data available in the numerous MHS data systems, the 
quality of that data and the methods for encrypting and collapsing data.  You 
may contact a data expert at the following email address: 
TMADataDetermination@tma.osd.mil) 
 
Yes, then complete the questions in this subparagraph b according to the 
information received from the data consult 
 
X No, then complete the questions in this subparagraph b according to the 
best of your knowledge (NOTE:  It is highly recommended to get a data 
consult). 
 
ii. Indicate whether you will receive a data extract from the MHS or will access a 
data system to create a data set. A data extract is when the MHS or a 
contractor provides the data set directly to the researcher. When receiving a 
data set through data extract, the researcher may indicate whether the data 

 
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elements should be provided as is, encrypted or collapsed.  In contrast to a 
data extract, access to a data system means that the researcher may access a 
data system and create a data set for the research study. 
 
Data Extract 
X Access 
 
iii. Do you intend to use only a de-identified data set in your research study? 
A de-identified data set is a data set that does not include any of the identifiers 
listed in the table in 5.5.5 (b)(vi).  In addition, the researcher does not have 
actual knowledge of another way the data can be used alone or in combination 
with other known information to identify an individual.  De-identified data is 
also data that a person, with appropriate knowledge of and experience with 
generally accepted statistical and scientific principles and methods for 
rendering information not individually identifiable, determines is not 
individually identifiable in accordance with the conditions outlined in 45 CFR 
164.514 (b)(1). 
Yes 
X No 
 
iv. Will you need MHS data with health information? 
Data with health information means any information that is created or 
received by the MHS that relates to the past, present or future physical or 
mental health or condition of an individual, the provision of health care to 
an individual or the past, present or future payment for the provision of 
health care to an individual.  Examples of MHS data with health 
information includes data maintained on AHLTA, CHCS and 
ESSENTRIS. 
 
X Yes 
No 
 
v. Do you intend to access a data base to obtain personally 
identifiable information that is not health information (PII)? 
 
X Yes, will access data base for (PII) 
 
No, will not access data base for PII 
 
vi. Include the following table in your protocol and put an “x” in the MHS 
column next to the categories of data that you are requesting from the MHS. 
If you are planning to receive a data extract of MHS data that includes a data 
element that will be deidentified by the MHS, then you do not need to put an 
“X” in the column corresponding to the category of data for that data 
element. 
 
Study 
Participant 
MHS 
Other 
1.  Names 
X 
2.  Postal address with only town, city, State and 
zip code 
X 

 
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3.  All geographic subdivisions smaller than a 
State, including street address, city, county, 
precinct, zip code and their equivalent 
geocodes, except for the initial three digits of a 
zip code if, according to the current publicly 
available data from the Bureau of Census: 1) 
the geographic unit formed by combining all 
zip codes with the same three initial digits 
contains more than 20,000 people; and2) the 
initial three digits of a zip code for all such 
geographic units containing 20,000 or fewer 
people is changed to 000. 
4.   All elements of dates (except year) for dates 
directly related to an individual, including birth 
date, admission date, discharge date, date of 
death; and all ages over 89 and all elements of 
dates (including year) indicative of such age, 
except that such ages and elements may be 
X 
X 
 
aggregated into a single category of age 90 or 
older 
5.  Telephone numbers 
X 
X 
6. Fax numbers 
7. Electronic mail addresses 
X 
8.  Social security numbers (In accordance with the 
DoD Social Security Number Reduction Plan, 
please justify the reason for collecting the social 
security number of study participants in the 
space after xi.) 
X 
X 
9.  Medical record numbers 
10.  Health plan beneficiary numbers 
11.  Account numbers 
12.  Certificate/license numbers 
13. Vehicle identifiers and serial numbers, 
including license plate numbers 
14.  Device identifiers and serial numbers 
X 
15. Web Universal Resource Locators (URLS) 
16.  Internet Protocol (IP) address numbers 
17. Biometric identifiers, including finger and 
voice prints 
18. Full face photographic images and any 
comparable images 
19. Any other unique identifying number, 
characteristic, or code (DEERs ID, EDIPN, 
Rank) 
 
vii. If you are requesting access to an MHS data system, put an “x” in the 
Request from MHS column next to the MHS system(s) from which you are 

 
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requesting data.  If you do not know what system contains the elements you 
intend to request, please refer to the Guide for DoD Researchers on Using 
MHS Data or seek guidance from a data expert. 
 
PHI Systems 
 
MHS Data Systems 
Request from MHS 
AHLTA 
X 
CDM (from the MDR) 
CHCS 
X 
ESSENTRIS 
X 
PDTS 
TRAC2ES 
M2 
MDR 
PDHRA 
PDHA 
TMDS 
 
PEPR 
JTTR 
 
PII Systems Only 
 
MHS Data Systems 
Request from MHS 
DMDC 
N/A 
MHS Learn 
N/A 
DMHRSi 
N/A 
 
De-Identified Data System 
 
MHS Data Systems 
Request from MHS 
EAS 
N/A 
 
Other Systems 
 
List Other system(s): 
N/A 
 
viii. Do you intend to merge or otherwise associate requested data with data from 
any other sources outside of MHS, including other DoD sources that are not 
part of the MHS? 
 
Yes, will merge data 
X No, will not merge data 
 
ix. Using the tables in 5.5.5 (b) (vi), put an “x” in the Other column next to the 
categories of data or data elements that include the data elements you intend 
to merge.  Not Applicable 

 
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x. Is there any possibility that the data will become identifiable because of 
triangulation, a small cell size, or any unique data element(s)? 
Triangulation means using different data elements that are not themselves 
identifiable but that in combination can be used to determine the identity of an 
individual.  For example, triangulation would be using rank and race together 
to determine the identity of an individual with a particular health condition. 
Small cell size means that the categories contain a small number of eligible 
individuals that satisfy the category description.  Guidance for acceptable cell 
size is available from the Centers for Medicare and Medicaid Services. For 
example, the rank category of five star generals with a particular diagnosis 
may be less than 30 so the data category may need to include lower ranks too. 
A unique data element includes any unique features that are not explicitly 
enumerated in the categories of data in Table vi above, but that could be used 
to identify an individual.  Examples of unique data elements include 1) a 
unique number, such as a medical record number or EDIPN; 2) a unique 
code, such as a diagnosis code or a bar code on electronic health record; and 
3) any unique characteristic, such as a high rank like general or admiral or a 
unique race or gender with another unique characteristic. 
Yes, there is a reasonable possibility the data will become identifiable.  
 
X No, there is no reasonable possibility the data will become identifiable. 
 
xi. Please justify the reason for collecting the social security number of 
study participants.  
We will collect the last four digits of the participants social security 
number for the purpose of accessing the medical record for chart review 
and verification of study data collected. 
 
5.5.6 Collection of Human Biological Specimens 
Human biological samples will be collected for this study; blood and tissue. 
 
Bloodwork: A blood sample (15 mls) will be drawn for hematological analysis 
including a CBC with differential panel, coagulation studies to include prothrombin 
time (PT) and international normalized ratio (INR) and comprehensive metabolic 
panel (CMP) at screening pre-treatment and at Week 1 post-ReCell treatment, which 
is consistent with standard of care practices. Samples will be labeled and processed 
by WRNMMC laboratory medicine per institutional policy. Therefore, these samples 
will be labeled with subject identifiers.  Additional laboratory testing will be 
performed only as clinically indicated. Any leftover blood from sample will be 
discarded per WRNMMC policy. 
 
Punch biopsy: A tissue sample size of 3mm diameter will be  obtained pre-treatment  
(baseline) from the INTEGRA™ MBWM treated wound site and adjacent normal 
skin and from the control and ReCell treated sites at at Week 2, 4 and 12 post-
ReCell treatment. All tissue samples will be coded and labeled with the subject’s 3-
digit ID number, date and time of harvest. Tissue samples will be cut in half with a 
sterile scalpel; one half of the sample will be preserved in 10% formalin by a member 

 
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of the study team then delivered to Annapath Inc. via courier pick-up for tissue 
processing, embedding (paraffin blocks), microtomy and slide preparation as per 
Annapath, Inc Technical Guidelines and Annapath, Inc Procedure Protocol (see 
Appendix F and  Appendix G).  The other half of tissue sample will be flash frozen 
with liquid nitrogen then stored in a -80° freezer with alarm system located within the 
Department of Orthopaedics Biomedical Lab Room 2010, Building 19 (America). 
 
As previously mentioned, one half of the tissue sample obtained for histology analysis 
will be frozen. The rationale for doing this is to preserve the ability to return to the 
frozen sample, if need be, in the event we do not get immunohistochemical analysis 
staining needed from the formalin fixed slides.  Oftentimes formalin fixed tissue does 
not perform as expected therefore, necessitating the need to freeze part of the sample 
to preserve options. The frozen samples will only be stored for evaluation within the 
period of funding for this research project then destroyed as per institutional policy 
standards. 
 
5.5.7 Banking of Human Biological Specimens 
This clinical trial does not involve the long-term storage (banking) of biological 
specimens. 
• 
Where and how specimens will be stored (including shipping procedures, 
storage plan, etc.): One half of the tissue specimen obtained from the surgical 
punch biopsies of the treated wound (performed at pre-treatment, Week 2, 4 and 
12) and of normal adjacent skin will initially be sent to Annapath, Inc. for 
processing (slide preparation and paraffin block embedding) as per Annapath, 
Inc Technical Guidelines and Annapath, Inc Procedure Protocol (see Appendix 
F and  Appendix G).  Annapath, Inc. will coordinate and dispatch its own 
courier for tissue specimen pick-up at WRNMMC. Annapath, Inc. will return all 
slides and paraffin blocks to WRNMMC for analysis and storage. The prepared 
slides and paraffin blocks will be housed in a locked cabinet within the 
Department of Orthopaedics Biomedical Lab Room 2010, Building 19 (America). 
The other half of the tissue specimen will be flash frozen with liquid nitrogen 
obtained from the WRNMMC Biomedical Research Laboratory (BRL) then 
stored in a -80° freezer with alarm system located within the Department of 
Orthopaedics Biomedical Lab Room 2010, Building 19 (America). 
• 
How specimens will be labeled (Specimens should be coded without any 
personal identifiers): No personal identifiers will be used in the coding of 
human specimens. All tissue samples will be coded and labeled with the 
subject’s 3-digit ID number. 
Who will have the access to the specimens, the clinical information, and the 
linkage: Annapath, Inc. laboratory staff will have access to coded tissue 
specimens up until the time they are processed and returned to WRNMMC. 
The study investigators will have access to the stored frozen samples, prepared 
slides and paraffin blocks. The information linking with the subject’s 3-digit ID 
number to the name of the participant will be kept by the Principal Investigator 
or designee in the study regulatory files in a locked cabinet. 
• 
How specimens will be used (general and/or specific use): The baseline 
histological analysis will examine the vasculogenesis and cytology of the 
regenerate before ReCell treatment. Serial samples will be analyzed to confirm 

 
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the thickness of new tissue and assess the normality of structures present in the 
newly regenerated skin. 
• 
Specify the length of time that specimens will be stored: The frozen samples 
and paraffin blocks will be housed in the Department of Orthopaedics 
Biomechanical Lab, Room 2010, Building 19 (America) and will be destroyed 
at the end of study completion. No specimens will be stored for future research. 
Slides will be stored according to institutional policy. 
• 
How the confidentiality will be protected at the storage and at the 
time of distribution: Please see section on confidentiality. 
• 
Whether subjects will be contacted and consented for future uses: At this 
time, we do not anticipate contacting subjects in the future for other uses of 
their stored tissue samples. 
Approval process for future studies: At this time, we do not have plans for future 
studies. Should this change, the PI will seek sub-protocol IRB approval for any 
future related studies. 
• 
How subjects may withdraw their specimens from storage: Research 
participants may request withdrawal/destruction of their tissue samples up until 
the time that they are used for histology analysis by asking a study investigator. 
Should any research participants withdraw from study participation, they will be 
specifically asked if their collected samples may be studied per protocol. 
This study will not obtain specimens from an existing bank/ repository, nor will there be 
any genetic research/testing. 
 
5.5.8 Study Time Line 
 
Please refer to Appendix J 
 
5.6 Investigational Drugs/ Investigational Devices 
 
5.6.1 Approval Status of Study Drugs 
 
Not applicable. 
 
5.6.2 Approval Status of Study Devices 
The ReCell device used in this protocol is investigational meaning that it is not approved 
by the Food and Drug Administration (FDA) for use in the United States. This research 
project is being conducted under an Investigational Device Exemption (IDE) application 
and the ReCell device is categorized as a Category B, Class III under the FDA 
regulations. The operative procedure for this study is considered a research procedure. 
 
The safety of ReCell has been demonstrated with over 5,000 treatment procedures 
conducted worldwide. ReCell has CE Marking in Europe, TGA clearance in Australia, 
SFDA clearance in China and Health Canada approval as well as approval in other 
markets (e.g., Taiwan, Hong Kong, Mexico, Brazil and Venezuela). There have been 
no reports of adverse events associated with the use of ReCell that have met the 
requirements for vigilance reporting to the respective regulatory authorities. 
 
Investigational Product: Autologous Cell Harvesting Device (ReCell) 

 
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 Dosing Instructions and Schedule: ReCell is supplied as a single use device.  The contents 
of    each kit are sufficient to prepare a cell suspension from a maximum biopsy size of 2cm x 
2cm to cover a wound area up to and including 320cm2 (Note: each square cm of skin sample 
will treat 80 sq cm of treatment area). 
 
Proposed Indication: ReCell is intended to be used at point-of-care for the safe and rapid 
preparation of epidermal and dermal cells as well as the cells at the epidermal-dermal 
junction from a small sample of the patient’s own skin. Under the provision of a 
healthcare professional, the cell suspension produced by the ReCell system is suitable for 
the treatment of partial-thickness wounds to promote re-epithelialization and for 
epidermal grafting over the INTEGRA™ MBWM. 
 
Investigational Device Description: The investigational ReCell Autologous Cell 
Harvesting Device has been developed to provide a simple, safe technique for the 
harvesting of epidermal cells for epidermal repair. ReCell is a single-use, stand-alone, 
battery operated, autologous cell harvesting device kit that contains enzymatic and 
delivery solutions, sterile surgical instruments, and actuators. The contents of each kit 
are sufficient to prepare a cell suspension to cover a wound area up to and including 
320cm2. 
 
This investigational device is used to disaggregate cells from a thin, shaved split- 
thickness skin biopsy sample obtained from the patient to be processed to produce a 
viable cell suspension for reintroduction to the patient. 
 
After the skin sample is taken, the ReCell suspension is available in under 30 minutes 
for immediate use onto a prepared wound surface and can cover a wound 80 times the 
size of the skin sample (a thin, split-thickness shave biopsy of 0.15 mm - 0.2 mm depth 
delivers a 1:80 expansion ratio; meaning the cell suspension produced from each 
square cm of skin sample will treat 80 sq cm of treatment area). The delivered cell 
suspension enables quick epithelialization of the wound, usually in 5 to 7 days a site-
matched skin sample allows reintroduction of the subject’s own skin cells that will 
develop natural texture, vascularity (pinkness) and pigment. 
 
The technology takes advantage of the regenerative capability of skin. Working with  
a small site-matched sample of the patient’s healthy skin, ReCell produces a cell 
suspension that stimulates skin growth.  The cell suspension, which is sprayed onto 
an affected area to be treated, contains the appropriate mixture of healthy cells to 
promote healing (keratinocytes), skin structure (fibroblasts), vascularity (colour), 
pigmentation (melanocytes) and texture. 
 
The investigational product must be stored, handled and administered in accordance with 
this protocol, the manufacturer’s IFU, as well as all applicable laws, regulations and 
institution requirements. 
 
The Investigator will ensure control of the investigational device. The 
investigational devices will be administered only to those subjects enrolled in this 
study under the supervision of the investigator and under the terms of the clinical 

 
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protocol and Investigator’s Agreement.  All clinical supplies and study devices 
intended for use in the clinical study cannot be used, under any circumstances, for 
any purpose other than described in the protocol. The investigator will also ensure 
that the device components are maintained under secure storage and that device 
accountability records are maintained. 
 
Investigational Device Accountability: 
The Avita Medical Americas, LLC will supply the investigator with an adequate number  
of investigational devices for completion of the study. The investigator is responsible for 
ensuring all investigational product accountability. Any discrepancies must be described 
in writing.  Throughout the study, device accountability records will be reviewed by the 
Sponsor’s appointed clinical monitor.  Records for dispensing study drug must be 
available for inspection by the clinical study monitor throughout the study. The 
investigator is responsible for ensuring that the device accountability records are 
complete and up to date at all times.  Regular study device reconciliation will be 
performed to document device assigned to subject enrollment number by the clinical 
monitor. 
 
The maintenance of study–related device accountability records does not preclude the 
Principal Investigator’s responsibilities to maintain additional records in accordance with 
all national and/or local institutional requirements for investigational device use. 
Receipt of Study Device: 
Arrangements will be made to have the investigational device kits shipped from the 
manufacturer directly to the Investigational Pharmacy Services at WRNMMC, to the 
ATTN: Dr. Parvenah Moussavian, Departmental Chief, where they will be housed until 
ordered by the investigator for use. 
 
The Principal Investigator, or a responsible party designated by the investigator, must 
maintain an inventory record to document the receipt and dispensation of each ReCell 
device kit. 
 
The investigational pharmacist will be required to keep records pertaining to the total 
number of ReCell device kits received from the manufacturer, date of receipt, condition 
of kits upon receipt, location and conditions of storage for both ReCell device kit and 
enzyme, until use in the operating room will be recorded on forms provided in the 
Pharmacy Manual.  Additionally, the investigational pharmacist will be required to 
record the lot number and expiration date for the Recell device kit and enzyme received. 
Any discrepancies must be described in writing. 
 
Upon receipt of the of the study device supplies, an inventory must be performed and a 
device receipt log filled out and signed by the person accepting the shipment.  It is 
important that the designated study staff counts and verifies that the shipment contains all 
the items noted in the shipment inventory.  Any damaged or unusable study devices in a 
given shipment will be documented in the study files. The investigator must notify the 
study sponsor of any damaged or unusable study devices that were supplied to the 
investigator’s site. 
 

 
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Investigational Device Packaging: 
TheReCell device kit contains the following items provided in sterile packaging:  
 
ReCell processing unit with built-in heating mechanism for warming the enzyme 
solution to optimum working temperature (+37C) 
 
Removable insert to act as a sterile Petri dish for use when preparing and scraping the 
skin biopsy 
 
ReCell Enzyme 
ReCell Buffer 
Water 
Syringes 
Needles 
Nozzles 
Scalpel 
 
Kits will be sealed with tamper resistant tape 
 
ReCell Device Kit Labeling: 
In accordance with The Code of Federal Regulations (CFR) 812.5 for investigational 
device labeling, the immediate package (outer box) of the ReCell kit bears the following 
information: 
 
• 
The name, address, telephone number, facsimile number and website address of 
the manufacturer, Avita Medical Americas, LLC 
• 
A separate label with the statement “CAUTION – Investigational Device 
Limited by Federal (or United States) Law to Investigational Use Only 
LBL090” 
• 
Listing of package/kit contents 
• 
Storage requirements to ensure stability of the investigational device and enzyme 
solution 
• 
Label with various symbols identifying relevant contraindications, hazards, 
warnings, and precautions. 
• 
Labels identifying investigational device kit date of manufacture, lot number and 
expiratory date of the product 
• 
Label stating lot number and expiration date for enzyme solution 
 
The ReCell kit and enzyme solution lot number and expiration date will be recorded in 
the eCRF. 
 
Storage and Handling (refer to IFU, Appendix A): 
The investigational device kits, including the enzyme (trypsin) will be maintained under 
controlled conditions. 
 
Upon receiving ReCell, the pharmacist should examine the packaging for external signs 
of damage or tampering.  If the external kit packaging or the packaging for any of the 

 
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individual components appears damaged, the kit should not be used. The pharmacist will 
be instructed to contact the investigator who in turn must notify the study sponsor of any 
damaged or unusable study devices that were supplied to the investigator’s site. 
 
To ensure stability of the device, storage requirements are as follows: 
 
Once the contents of the kits have been inspected, the investigational pharmacist will 
remove the enzyme (trypsin) from each kit and immediately refrigerate at 2-8ºC (35.6-
46.4°F).  The investigational pharmacist will be required to maintain a daily temperature 
log to record the temperature of the refrigerator where the enzyme is being stored. Any 
discrepancies must be described in writing. 
    
All other components are to be stored at room temperature. 
Dispensing of Investigational Device: 
The investigational product (ReCell device) will not be applied to any person who is not 
a qualified study participant under this protocol.  The ReCell device will be dispensed 
only by study site personnel designated by the Principal Investigator on the study site 
Delegation Log. 
 
An order for the ReCell kit will be written by the Investigator and sent to the WRNMMC 
investigational pharmacy to request the treatment ReCell device kit for availability on the 
scheduled day of surgery for the subject enrolled. 
 
When needed, the pharmacist will dispense 2 kits to a member of the research team. One 
ReCell kit will be dispensed for use and the other will be obtained for the purpose of 
having “on-hand” in the event of a device malfunction while in the operating room. The 
investigational pharmacist will record dispensing of both device kits. One kit will be 
denoted as “intended for use” and the second kit will be denoted as the “back-up device” 
in the device accountability log.  If the second device deemed as the “back up device” 
was not needed, it will be returned to the investigational pharmacy by the study 
coordinator and logged back in on the device accountability log to be dispensed for future 
use with the next subject enrolled. Stringent record keeping of this dispensing process 
will be maintained for investigational device accountability. 
 
The clinical site will utilize an investigational product accountability log provided by the 
manufacturer.  The following information will be recorded on the log by the designated 
individual dispensing the investigational product: date investigational device(s) were 
dispensed and initials of device dispenser, subject number and lot number for device kits 
dispensed and documentation regarding date and lot number of returned “back-up 
device”, if applicable. 
 
Return or Destruction of Investigational Device: 
At the completion of the study, there will be a final reconciliation of study devices 
shipped, devices consumed, and devices remaining.  This reconciliation will be logged on 
the device reconciliation form, signed and dated by the Principal Investigator and the 
Investigational Pharmacist.  Any discrepancies noted will be investigated, resolved, and 
documented prior to return or destruction of unused study devices. 

 
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ReCell and all individual components included in each kit are intended for single use 
only. Used ReCell devices and kit components will be discarded into appropriate 
biohazard receptacles after single use. Devices destroyed on site will be done in 
accordance with manufacturer recommendations, institutional policies and procedures 
and documented in the study regulatory files. Unused (including expired) investigational 
devices are to be returned to the manufacturer,  Avita Medical Americas, LLC  via use 
of their established Return Material Authorization (RMA) process. Per manufacturer 
directives, to return all unused investigational device kits, the study site will notify the 
manufacturer. They in turn will generate and send site an Investigational Device Return 
Form along with a return FedEx air bill to cover return shipment fees. The devices will 
be returned to the address below: 
 
Return to: 
Avita Medical 
c/o Parker Hannifin Corp 
ATTN: Customer Service 
3007 Bunsen Avenue, Suite L 
Ventura CA 93003 
Telephone: 818) 356-9419 
5.7 Statistical Considerations 
 
5.7.1 Study Endpoints                                                                                                                                         
 
Primary Outcomes: Safety and Tolerability 
  The safety and tolerability endpoints for this feasibility clinical trial includes: 
 
• Delayed healing/non-healing of wound and donor site 
• Graft loss 
• Heterotopic ossification 
• Infection 
• Scar contracture 
• Durability (i.e. abrasions/injuries at graft site due to graft fragility) 
• Allergic response to trypsin (the enzyme used in the ReCell process) 
• Subject Complaint (i.e. pain and itching) 
• Vital Signs 
• Blood chemistries and hematology 
• Treatment-related adverse events requiring surgical intervention prior to Week 12 
post-treatment and all serious adverse event (SAE) occurrences throughout the 
study 
   
Secondary Outcomes:  Preliminary and Long-Term Efficacy  
The preliminary efficacy (Week 1-6 post-treatment) endpoints for this feasibility clinical 
trial includes: 
 

 
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• Wound epithelialization 95% or greater re-epithelialization at treated wound site and 
donor sites 
• Histology 
• Patient pain rating 
 
The long-term efficacy (Week 12 and 24 post-treatment) endpoints for this feasibility 
clinical trial includes: 
 
• Scar assessment scale using the Patient and Observer Scar Assessment Scale 
(POSAS) and Vancouver Scar Scale 
• Functional outcome rating 
• Patient satisfaction 
• Histology 
•  Radiographic evaluation for assessment of heterotopic ossification 
 
5.7.2 Sample Size Estimation 
No formal sample size estimation has been performed since this is a feasibility study. A 
sample size of 20 subjects was selected based upon the amount of subject exposure 
considered necessary in order for clinical assessments of safety, tolerability, preliminary 
and long-term effectiveness of the ReCell device when used for healing of full-thickness 
wounds treated with 1:5 meshed STSG and INTEGRA MBWM. This study does not 
evaluate formal hypotheses and is not prospectively powered to detect potentially 
clinically significant improvements in study endpoints. The results of this feasibility 
study may be analyzed to refine the study design for a pivotal trial. 
 
5.7.3 Data and Statistical Analysis Plan 
Due to the feasibility nature of this clinical trial, no formal statistical analysis nor 
interim analysis will be performed.  Data collected in this study will be documented 
using summary tables. Quantitative variables will be summarized using descriptive 
statistics, including mean (and/or median), standard deviation (SD), and when 
appropriate minimum and maximum values. Categorical variables will be summarized 
by frequencies and percentages. Where appropriate, 95% confidence intervals either 
around the sample means or mean differences will be furnished. All data collected will 
be presented in subject data listings. 
 
Power Analysis 
Post hoc power analysis was conducted using G*Power 3.1 (Faul, Lang, & Buchner, 
2007) for this 2 x 7 mixed design (i.e., two treatment groups x 7 waves of measurements). 
Given the constraints on sample size (n = 20), a power analysis was conducted with the 
intent to detect the obtained power (1 – β) given: (1) level of significance (set at α = .05), 
effect size (standardized F statistic varied at .15, .2, and .25) and (3) rate of 
autocorrelation (average correlations of repeated measures varied at .3, .5, and .7).  Even 
though ascertaining what constitutes a small/medium/large effect size is, in part, context 
and discipline-dependent, using Cohen’s (2008) taxonomy of small (F = .10) and  
medium (F = .25) we see below that sufficient power (.80) to obtain significance for the 2 
x 7 first order interaction will be obtained for a medium effect size when the 
autocorrelation is .5 or higher and for a slightly smaller effect size (F = .2) when 
autorcorrelation approximates .7.  However if the effect size approximates .15 sufficient 

 
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power will not be obtained, regardless of magnitude of autocorrelation. 
 
AutoCorr Effect Size 
Power 
0.3 
0.25 
0.729 
0.5 
0.25 
0.881 
0.7 
0.25 
0.989 
0.3 
0.2 
0.503 
0.5 
0.2 
0.672 
0.7 
0.2 
0.904 
0.3 
0.15 
0.286 
0.5 
0.15 
0.399 
0.7 
0.15 
0.639 
 
Faul, F., Erdfelder, E., Lang, A.-G., & Buchner, A. (2007). G*Power 3: A flexible statistical power analysis 
program for the social, behavioral, and biomedical sciences. Behavior Research Methods, 39, 175-191. 
Cohen (1988). Statistical power analysis for the behavioral sciences. (2nd Ed.). Hillsdale, NJ: Lawrence 
Erlbaum. 
 
Proposed Analysis 
For this 2 x 7 mixed design (i.e., two treatment groups x 7 waves of measurements) with 
a continuous level outcome, a two-way (completely within) repeated measures ANOVA 
will be performed with the overarching objective being the test of significance for the 
two–way treatment x time interaction (using α = .05).  If the two-way interaction is 
significant, simple effects analysis will be performed so as to assess at which time point 
significant differences for the treatment variable are obtained.   Moreover, if the first 
order interaction is significant, trend analysis will be conducted in an effort to uncover 
any nonlinear patterns across time (up to polynomial t – 1, where t = time). Graphic 
displays will be provided so as to illuminate the nature of the findings and the between 
treatment trajectories.   
 
All assumptions will be examined, including sphericity and homogeneity of 
variance/covariance matrices and any data anomalies (e.g., outliers) will be examined 
and treated accordingly.  It should be kept in mind that given the small sample size (n = 
20), there may still be substantive effects despite non-significant results, hence univariate 
and multivariate effect sizes will be reviewed (e.g., partial η2). 
 
There are many techniques beyond a mixed ANOVA approach that can more 
dynamically model the longitudinal nature of this design, such as multilevel modeling, 
generalized estimating equations, and/or latent growth curve modeling. However, those 
techniques will need to be deferred until a larger sample size is obtained. All analysis 
will be conducted using SPSS 21.0 or Stata 11.0. 
Analysis Sets of ReCell Device Treatment vs. Control Comparison: 
Safety Analysis Set: 
The safety analysis population will include all enrolled subjects .  Data will be analyzed 
based on treatment received.  The number and percentage of subject who discontinued 
the study due to adverse event will be provided. Also, descriptive statistics, as 

 
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appropriate, will be provided for the following, by treatment: 
• 
Delayed healing/non-healing of wound and donor site 
• 
Graft loss 
• 
Heterotopic ossification 
• 
Infection 
• 
Scar contracture 
• 
Durability (i.e. abrasions/injuries at graft site due to graft fragility) 
• 
Allergic response to trypsin 
• 
Subject Complaint (pain and itching) 
• 
Vital Signs 
• 
Blood chemistries and hematology 
• 
Safety-related issues occurring through 24 weeks after treatment, other treatment- 
related adverse events requiring surgical intervention prior to 12 weeks post- 
treatment and all serious adverse event (SAE) occurrences. 
 
For Adverse Events (AEs), a tabulation of incidence, number of subjects and percent of 
subjects experiencing AEs will be provided for: 
 
• Serious AEs 
• Severity 
• Expected or Unexpected 
• Relationship to Study Treatment 
• Body System and preferred term 
 
A listing of all AEs along with severity, relation to treatment, date and outcome will also 
be provided. 
Effectiveness Analysis Set: 
Preliminary and long-term effectiveness data will be summarized descriptively for each 
of the assessment intervals by presenting the number and proportion of treatment and 
donor sites that achieved healing. The treated wound site will be considered healed if 
95% or greater re-epithelialization has occurred by Week 6 post-treatment. Donor sites 
(STSG 1:5, STSG 1:1.5 and ReCell) will be considered healed when ≥ 95% of the donor 
site has re-epithelialized by Week 4 post treatment.  Both Observer and Patient 
Assessment scales of the POSAS, and total POSAS scores will be summarized 
descriptively (mean, median, standard deviation, range) at Weeks 12 and24. The 
Vancouver Scar Scale (VSS) assessment tool and total VSS scores will also be 
summarized descriptively (mean, median, standard deviation, range) at Weeks 12 and 
24. Patient satisfaction and functional outcome ratings data will be summarized in 
terms of counts, percentages and other descriptive statistics. 
 
Histology Analysis 
Histological analyses will be performed on punch biopsies of ReCell-treated and control 
sites for Week 2, 4 and 12 and also of the pre-treatment biopsies taken from the 
INTEGRA™ MBWM treated wound site and adjacent normal skin. This biopsy of 

 
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normal skin serves as the control control for all other biopsies.  At each assessment 
interval, histological parameters from both ReCell-treated and control biopsies will be 
compared to the same parameters as measured in normal skin.  Data will be 
summarized descriptively. 
 
Cell Suspension Preparation/Application Parameters Analysis 
Data concerning biopsy size and thickness, wound size, and ReCell cell suspension 
application (e.g., volume and details for application) will be documented on the 
eCRF. Data will be summarized using descriptive statistics. 
 
Demographic Data Analysis 
Tabulation of demographic data will be tabulated by age, gender and race/ethnicity. 
 
Study Termination Analysis 
The following analysis will be provided pertaining to Study Termination: 
 
• Number and percent of subjects who completed the study 
• Frequency of premature termination reasons 
• A listing of all subjects who were prematurely terminated from the study along with 
the reason and date of early termination 
 
The following will be considered as major protocol deviations: 
 
• Major inclusionary/exclusionary deviations 
• Missed visits/assessments such that a determination of healing status at both wound 
sites and ReCell donor site cannot be determined 
• Significant protocol non-compliance that may confound evaluation of healing (e.g. 
use of inappropriate primary dressing) 
 
Any significant deviations to the statistical analysis plan will be addressed in the final 
report for this study. 
 
  Randomization: 
Allocation of treatments to the 2 defined wound regions at the INTEGRA™ MBWM   
treated wound sites will be done at random, using a computer generated randomization 
table provided by Glaser Consulting.  Wound regions will initially be labeled “A” region 
and “B” region by the surgeon, and then an envelope will be opened which will indicate 
which treatment (ReCell or control) to assign to “A” region and which treatment to assign 
to “B” region. Randomization envelopes containing treatment region allocation will be 
opened in chronological order corresponding to subject enrollment. 
 
Example Randomization Table 
 
 SUBJECT #             TREATMENT ASSIGNMENT 
 DERM- 001          A Region (ReCell)  B Region (Control) 
 
 DERM- 002          A Region (ReCell)  B Region (Control) 
 

 
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 DERM- 003          A Region (Control)  B Region (ReCell)   
 
6.  HUMAN SUBJECT CONSIDERATIONS 
 
6.1 Anticipated Benefits 
ReCell is designed to provide an environment to enhance skin regeneration, and to 
facilitate rapid wound healing, providing the potential to eliminate or minimize scar 
formation. By introducing an autologous epidermal cell suspension onto a wound 
surface, the ReCell technology takes advantage of, and enhances, the body’s natural 
regenerative response to heal itself. 
 
Wounded service members frequently possess limited donor site availability due to 
the nature and extent of associated injuries and therefore harvest sites for the split-
thickness skin grafting is often limited. The ReCell Autologous Cell Harvesting 
System (ReCell device) allows autologous transplant of the patient’s own skin cells, 
including epidermal progenitor cells using a small thin biopsy site (typically no 
larger than 2 cm by 2 cm). Used in combination with a meshed split-thickness skin 
graft (STSG) over INTEGRA™ MBWM, ReCell should allow for an expanded 
meshing ratio, thereby decreasing the required donor site. With the direct 
application of autologous epidermal progenitor cells the technology also offers the 
potential to promote faster healing, minimization of mesh patterned scar and 
improved patient quality of life. 
 
ReCell has been demonstrated to deliver viable keratinocytes, melanocytes, fibroblasts 
and Langerhans cells to the wound surface. Preliminary clinical data demonstrate that 
wounds treated with ReCell rapidly re-epithelialize with reduction of systemic effects, 
wound infection or adverse reactions, yield improved scar texture, reduce contracture, 
heal free of erythema and achieve re-pigmentation at the treatment site. 
 
Subjects participating in this clinical research trial may or may not derive a direct 
benefit from study participation.  Although we cannot guarantee a positive outcome 
from this research project, validating the safety and preliminary efficacy of this 
treatment could provide a new approach in regenerative medicine.  Increased 
knowledge and technological advancement may result from the conduct of this 
research study and potentially help a large number of individuals in the future. 
 
6.2 Risks and Discomforts 
Subjects will be monitored for safety from time of enrollment to conclusion of study 
visits. All adverse events will be collected by direct subject communication with 
investigator/study coordinator and review of source documents. 
 
Any conditions or symptoms reported after the subject receives investigational product 
will be recorded as an adverse event (AE) on the AE eCRF. This includes new events 
after study device administration, conditions that become more severe or increase in 
frequency, any disease-related signs or symptoms present at the Screening Pre-Treatment 
visit that have worsen in severity or frequency, as well as any event or finding that the 
Investigator feels is clinically significant. 
 
At each post-treatment visit, subjects will be asked by the PI and/or AI about any AE’s 

 
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they have experienced since the previous visit. Any adverse condition or symptom 
reported will be reported and recorded as an AE in the subject’s source documents and 
on the AE eCRF page.   The subject will be instructed to contact the study site in the 
event they experience any significant AE’s.  At the discretion of the Investigator, the 
subject may be asked to come to the study site for an unscheduled visit.  
 
There are no known risks of the ReCell device based on results from over 5,000- 
treatment procedures conducted worldwide. Potential risks to the volunteer that will 
be monitored may include: delayed healing/non-healing of wound and donor site, 
graft loss or rejection, heterotopic ossification, infection, scar contracture, durability 
(i.e. abrasions/injuries at graft site due to graft fragility), allergic response to trypsin, 
and other treatment-related adverse events requiring surgical intervention prior to 12 
weeks post-treatment. 
 
• 
Rare but serious (Event Rate < 1%) 
o Death, side effects and complications from anesthesia, allergic response 
to trypsin, allergic response to lidocaine used prior to the biopsy 
procedure and radiation exposure for radiographic imaging for 
assessment of heterotopic ossification 
• 
Less Likely (1% ≤ Event Rate < 5%) 
o Keloid formation, infection at wound site or donor sites, reduced or loss 
of skin sensation or increased sensitivity, scarring, skin discoloration, 
uneven skin surface 
• 
Likely (5% ≤ Event Rate < 10%) 
o Discomfort, bruising, bleeding with phlebotomy at site of blood draw 
and/or punch biopsy, scar contractures that impact limb function, total 
graft loss 
• 
More likely (Event Rate ≥ 10%) 
o Heterotopic ossification, partial graft loss. Greater than 65% of combat 
casualties develop heterotopic ossification as a result of their injuries. A 
number of wounds may develop HO as a result of the initial trauma and not 
directly caused by the application of STSG or ReCell spray skin.  
 
Risk Analysis  
 
Anticipated Risks 
The potential risks to the subject arising from the biopsy collection and grafting 
procedures, and from exposure to the ReCell Device, are analyzed in the tables 
below. 
 
Risks and Mitigation Strategies for ReCell® Autologous Cell Harvesting Device 
Potential Risks 
Mitigation Strategies 

 
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Allergic reaction to 
anesthesia, 
medications, or 
device 
• 
Enrollment will be restricted to subjects with no known allergies 
to study materials (device, anesthesia, and/or medications) 
• 
Post-operative assessment of allergic response performed 
throughout the study period 
Viral transfer from 
animal enzyme 
• 
Trypsin has been extensively tested for viruses and undergone 
viral elimination processes which have been validated 
  Potential Risks 
                                       Mitigation Strategies 
Risks related to tissue response at Donor and Treatment Sites 
Infection 
• 
Instructions for use (IFU) detail wound bed preparation 
procedures 
• 
Patients with active infection are excluded from the study 
• 
Sterile study equipment 
• 
Study procedures are performed according to aseptic principles 
required during surgery and post-operative dressing changes 
• 
IFU allows for the use of prophylactic, perioperative antibiotics 
as part of the surgical management process 
Rejection / loss of 
graft 
• 
Cell material is autologous 
• 
IFU reinforces use of aseptic principles 
• 
Patient selection (i.e., exclusion of patients known to have a pre- 
existing condition that may interfere with wound healing) 
 
Excessive bleeding 
at donor site 
• 
IFU details biopsy harvesting processes (including infiltration 
with adrenaline) 
Lack of take of 
graft 
• 
IFU details wound site preparation requirements 
• 
IFU contraindicates infection in wound site 
Cross 
contamination 
• 
ReCell Device is single use and is marked as used at 5 minutes 
post incubation commencement preventing further restarts 
• 
Only one vial of Trypsin is included with each device 
• 
IFU details that ReCell is for autologous use only 
Worsening Scar 
• 
IFU/protocol details instructions for proper 
dressing/management of treatment and donor wounds. 
Risks related to Biopsy Processing 
Biopsy separation 
not possible 
• 
Trypsin extensively tested and released following assessment of 
activity 
• 
Incubation of biopsy takes place at ~36.5°C which is within the 
optimal temperature for Trypsin activity 
• 
IFU details troubleshooting strategies for difficult to separate 
biopsies 
• 
IFU details procedures for harvesting suitable biopsies 
• 
IFU details that Trypsin is to be reconstituted with Water For 
Injection (WFI) and warn that reconstitution with Compound 
Sodium Lactate for Irrigation (CSLI) may impact enzyme 
activity 

 
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Cell viability low 
• 
IFU details that biopsy should not be exposed to Trypsin for 
longer than 60 minutes 
• 
IFU describes the cell scraping process to maximize cell quantity 
isolation 
• 
Conical well has been designed into processing unit to allow for 
maximal cell draw-up post filtration 
• 
Biopsy incubation occurs at ~36.5°C which is within the optimal 
temperature for Trypsin activity.  Device is fitted with alerts if 
this temperature is exceeded 
 
Potential Risks 
Mitigation Strategies 
No or minimal 
epithelialization due 
to improper 
processing, cell 
suspension 
application, 
inadequate cell 
suspension volume 
or inadequate 
healing 
• 
IFU detailing biopsy size requirements 
• 
IFU detailing biopsy processing steps and troubleshooting 
measures 
• 
IFU detailing correct cell dilution 
• 
IFU detailing maximum time frame for biopsy exposure to 
Trypsin 
• 
IFU detailing contraindications for biopsy sites such as infection 
• 
Patient selection excludes patients with pre-existing infections. 
• 
IFU detailing correct dressing materials to be used and time 
frames and processes for replacing dressings so as not to damage 
healing wounds on dressing removal 
• 
Patient selection (i.e., exclusion of patients known to have a pre- 
existing condition that may interfere with wound healing) 
Risks related to cell application 
Nozzle blockage 
• 
Nozzles designed with an aperture which allows for cells to pass 
through easily 
• 
100 micron filtration occurs prior to spraying of cells 
• 
Spare nozzle supplied with each device 
Nozzle aperture 
position 
• 
IFU recommend test spray 
• 
IFU describes aperture positioning 
 
The potential risks to the subject and adverse events associated with use of the ReCell 
Device discussed in the tables above are minor and easily controlled. 
 
 Adverse Event Evaluations and Reporting 
Subjects will be monitored for safety from time of enrollment to conclusion of study visits. 
All adverse events will be collected by direct subject communication with 
investigator/study coordinator and review of source documents. 
 
At each post-treatment visit, the research team will assess if the subject has experienced 
any adverse effects post-treatment with the investigational device.  The subject will be 
asked if he/she has any problems, issues and/or concerns since the last encounter visit that 
could be potentially related to study participation.  Any conditions or symptoms reported 
after the subject receives investigational product will be recorded as an adverse event (AE) 
on the AE eCRF. This includes new events after study device administration, conditions 

 
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that become more severe or increase in frequency, any disease-related signs or symptoms 
present at the Screening Pre-Treatment visit that have worsen in severity or frequency, as 
well as any event or finding that the Investigator feels is clinically significant. 
 
Other treatment-related adverse events requiring surgical intervention prior to Week 12 
post-treatment and all serious adverse event (SAE) occurrences will be treated and 
recorded in the eCRF.  For all adverse events, the Investigator will provide an assessment 
of the event, its treatment resolution, and relationship to the investigational device. 
Subjects who have an ongoing AE related to the study device at Week 24 post-treatment 
will be followed for 30 days until resolution and/or stabilization of the event at a level 
acceptable to the Investigator. 
 
Adverse Event Definitions: 
 
Identification of Adverse Events (AEs), Adverse Device Effects (ADEs)An adverse 
event is defined as any new medical problem or exacerbation of an existing problem, 
experienced by a subject while enrolled in the study after receiving investigational product, 
whether or not it is considered related to the investigational device by the Investigator. 
 
Treatment-Related Adverse Event 
A treatment-related adverse event is an adverse event that is judged to be related to the 
investigational device, study therapy and study-related procedures. 
 
Unexpected Adverse Event 
An unexpected adverse event is any adverse effect which the frequency, specificity or 
severity is not consistent with the risk information described in the investigational plan. 
Anticipated (Expected) Adverse Event 
Potential adverse event that a subject may experience following the use of the ReCell 
device as described in this section above and using the potential risks listed in the above 
tables. 
 
Definitions of Specific Major Treatment –Related Adverse Events: 
Infection: The presence of infection for the ReCell treated areas and control site will be 
evaluated at each post-treatment visit. Infection will be evaluated in accordance with the 
Center for Disease Control (CDC) guidelines for nosocomial infections using standard 
clinical measures such as visual examination of the treatment sites for delayed healing, 
redness, inflammation and surrounding cellulitis. In the presence of symptoms (i.e., 
purulent exudate, changes in wound appearance such as hyperemia, and erythema in the 
uninjured skin surrounding the wound), infection will be confirmed using microbiological 
testing procedures and treatments initiated according to the institutions’ infection 
management protocols, which will be recorded on the eCRF and Adverse Event form.   
Infection will be managed according to the standard protocols of the clinical site.  For 
example, treatment of infection will involve the daily cleaning and dressing of wound sites 
until such time that the infection is clear.  Treatment with broad spectrum antibiotics until 
microbiology sensitivities return from the testing laboratory is recommended.  Upon return 
of sensitivities, antibiotic therapy may either continue as is, or be changed at the discretion 
of the investigator.  All treatment regimens applied in the management of infection will be 
recorded on the eCRF. 

 
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Allergic Response to Trypsin: The allergic response to Trypsin, the enzyme used in the 
ReCell Device for disaggregation of the biopsy, will be evaluated.  An allergic response to 
Trypsin is most likely to present as contact dermatitis (defined as an altered state of skin 
reaction induced by exposure to an external agent). Substances that produce this condition 
after single or multiple exposures may be irritating or allergic in nature and induce an 
inflammatory response.  The most common clinical expression of this induced 
inflammation is dermatitis (eczema).  
The evaluation tools for assessment of the allergic response to Trypsin have been 
developed in accordance with guidelines published in the Journal of the American 
Academy of Dermatology.  The subject will be evaluated at each post-treatment visit for 
any occurrences of an allergic reaction (e.g. eczema/dermatitis).  Any allergic response(s) 
to trypsin will be recorded in the eCRF and depending on severity, will have an additional 
reporting to the IRB, Research Monitor and study report.  
 
The incidence of adverse response to Trypsin is expected to be low.  
Other Treatment-Related Adverse Event Requiring Subsequent Surgical Intervention 
 
Any treatment-related adverse event resulting in subsequent surgical intervention (e.g., 
“graft loss” requiring retreatment) will also be considered a major treatment-related adverse 
event. 
 
The incidence of other treatment-related adverse events requiring subsequent surgical 
intervention is expected to be low. 
 
Clinical investigators and ultimately the Principal Investigator will be responsible for AE 
identification, documentation, grading and assignment of attribution to the investigational 
device. 
 
All observed or volunteered adverse effects (serious or non-serious) and abnormal test 
findings deemed clinically significant by the investigator, regardless of treatment group, if 
applicable, or suspected causal relationship to the investigational device or, if applicable, 
other study treatment or diagnostic product(s) will be recorded in the subjects’ eCRF.  
Criteria for grading of adverse events will be as defined by the Common Terminology 
Criteria for Adverse Events (CTCAE) version 4.0 
(http://www.uptodate.com/contents/common-terminology-criteria-for-adverse-events).  For 
all adverse effects, sufficient information will be pursued and/or obtained so as to permit 1) 
an adequate determination of the outcome of the effect (i.e., whether the effect should be 
classified as a serious adverse effect) and; 2) an assessment of the casual relationship 
between the adverse effect and the investigational device or, if applicable, the other study 
treatment or diagnostic product(s). 
 
Severity 
Each adverse event will be assessed for its severity, or the intensity of an event experienced 
by the subject, using the Common Terminology Criteria for Adverse Events (CTCAE), 
v4.0. The CTCAE grading (severity) scale will be utilized for each AE based on the 
following: 

 
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Grade 1 = Mild: Asymptomatic or mild symptoms; clinical or diagnostic observations 
only; intervention not indicated, discomfort noticed, but no disruption to daily activity 
 
Grade 2 = Moderate: Minimal, local or noninvasive intervention indicated, discomfort 
sufficient to reduce or affect normal daily activity 
 
Grade 3 = Severe: Medically significant but not immediately life-threatening; 
hospitalization or prolonged hospitalization indicated; disabling, inability to work or 
perform normal daily activity 
 
Grade 4 = Life-threatening: Urgent intervention indicated 
 
Grade 5= Death: Death related to an adverse event 
 
Relationship of Adverse Events to the ReCell Investigational Device 
The Investigator should assess the relationship of the adverse event to the investigational 
device.  The relationship should be assessed using the following categories: 
• 
Definitely Related: 
A direct cause and effect relationship between the investigational 
device/treatment and the adverse event exists. 
• 
Likely Related: 
A direct cause and effect relationship between the investigational 
device/treatment and the adverse event has not been clearly demonstrated, but 
is likely or very likely. 
• 
Unlikely Related: 
A direct cause and effect relationship between the investigational 
device/treatment and the adverse event is improbable, but not impossible. 
• 
Unrelated: 
The adverse event is definitely not associated with the investigational 
device/treatment. 
 
Outcome 
The Investigator will categorize the outcome of the adverse event using the 
following definitions: 
Resolved: The subject recovered from the adverse event. 
Resolved with sequelae:  The subject recovered, but with an after effect possibly 
due to disease, injury, treatment, or procedure. 
Ongoing: At the time of the last assessment, the event is ongoing, with an 
undetermined outcome. 
Death: The adverse event directly caused death. 
Unknown: There is an inability to access the subject or the subject’s records to 
determine the outcome (i.e., subject withdrew consent or is lost to follow-up) 
 
Unanticipated Adverse Device Effects (UADEs) 
An unanticipated adverse device effect is defined as “any serious adverse effect on 

 
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health or safety, or any life-threatening problem, or death caused by, or associated with, 
a device; if that effect, problem, or death was not previously identified in nature, 
severity, or degree of incidence in the investigational plan, or application (including 
supplementary application), or any other unanticipated serious problem associated with a 
device that relates to the rights, safety, or welfare of subjects.” 
 
If an unanticipated adverse device effect occurs, the investigator must report the event 
promptly to the Sponsor, the IRB and Medical Research Monitor via email or telephone 
within 24 hours of first learning of the event. The Sponsor will conduct an evaluation of 
the unanticipated adverse device effect and will provide a written report the results to 
FDA and to all reviewing IRBs and participating investigators within 5 working days. 
   
Such reports will also be promptly reported by telephone (301.619.2165), by email 
(usarmy.detrick.medcom-usamrmc.other.hrpo@mail.mil), or by facsimile (301.619.7803) 
to the Human Research Protection Office (HRPO). A complete written report should 
follow the initial notification (Please refer to Section 6.4 below) 
   
Serious Adverse Events (SAEs) 
Each adverse event should be assessed for its seriousness using the criteria outlined 
below.  The term serious adverse event is not synonymous with a “severe” adverse event, 
which may be used to describe the intensity of an event experienced by the subject. 
An adverse event should be classified as an SAE if it meets any of the following criteria: 
• 
Results in, or contributes to, a death 
• 
Life-threatening (i.e., the subject was, in the opinion of the investigator, at risk of 
death at the time of the event, but it does not include an event that, had it occurred 
in a more severe form, might have caused death) 
• 
Results in permanent disability or incapacity (i.e., permanent impairment of a 
body function or permanent damage to a body structure) 
• 
Requires in-subject hospitalization or prolongs hospitalization 
• 
Necessitates medical or surgical intervention to preclude a permanent disability or 
incapacity 
• 
Results in a congenital anomaly or birth defect 
Non-serious adverse events are all events that do not meet the criteria for a “serious” 
adverse event. 
 
Deaths 
The Principal Investigator must notify the IRB (via IRBNet) and the sponsor of the IDE 
within 24 hours of first learning of a subject’s death, regardless of whether the death is 
related or unrelated to the investigational device.  The Investigator should attempt to 
determine, as conclusively as possible, whether the death is related to the device. The 
cause of death and the Investigator’s discussion regarding whether or not the death was 
device-related should be described in a written report.  Serious adverse events must be 
reported even if the PI believes that the adverse event is unrelated to the protocol. 
 
6.3 Actions to Minimize Risks 

 
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a. Safety Monitoring Plan 
Based on trials conducted with the ReCell device, no significant participant risks 
are anticipated and no interim analysis is planned; therefore, there are no pre-
specified stopping rule procedures planned for this clinical trial.  However, if any 
serious safety issues do arise, medical judgment will be used and the Investigator 
will, in consultation with the Medical Research Monitor, the Sponsor, appropriate 
regulatory authorities, and/or IRB, take steps necessary to modify or discontinue 
the trial. 
 
b. Safety Analysis Plan: The IRB, medical research monitor, and principal 
investigator will review any safety concern. A data safety monitoring board 
(DSMB) is not required for this study. Safety concerns will be analyzed by the PI 
and medical research monitor to avoid unnecessary exposure of subjects to 
ineffective or dangerous interventions. Patients may be discontinued from 
participation in the study in the presence of exclusion criteria or at the 
recommendation of the Principal Investigator or by the study medical research 
monitor (Carlton Brown, MD). 
The medical research monitor will function as an independent safety advocate for 
subjects enrolled into this clinical trial. The medical research monitor is required 
to review all unanticipated problems involving risk to subjects or others, SAEs, 
and all subject deaths associated with the protocol and provide an unbiased 
written report of the event. At a minimum the medical research monitor should 
comment on the outcomes of the event or problem and, in the case of a SAE or 
death, comment on the relationship to participation in the study. The medical 
research monitor should also indicate whether he concurs with the details of the 
report provided by the study investigator. Reports for events determined by either 
the investigator or medical research monitor to be possibly or definitely related to 
participation and reports of events resulting in death should be promptly 
forwarded to the IRB and/or ORP and USAMRMC CSSD PSSB (sponsor safety 
office). 
c. Confidentiality Protection 
Any personal information that could identify the subject as an individual will be 
removed from all study forms. Upon enrollment, the subject will be assigned a 3- 
digit study ID number that is not a part of their social security number.  All 
information collected for the purpose of this study will be coded using the 
subject’s 3-digit study ID number and will be used on all study data collection 
forms and eCRF’s. The link between subject’s name and their study ID number 
and initials will be kept confidential to the greatest extent provided by law.  The 
master list linking the subject’s 3-digit study ID number and their identifying 
information will be kept by the Principal Investigator (or his designee) in a locked 
file cabinet located in the Orthopaedic Surgery clinic at WRNMMC. 
 
Study records and digital photographs will be maintained in a locked file cabinet 
in a locked room located in the Orthopaedic Surgery clinic at WRNMMC 
accessible only to personnel involved with this study. Precautions are in place to 
ensure all electronic records will be stored in password-protected encrypted files. 
Access to this information will be limited to research team members and to those 

 
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health care professionals who are providing clinical services as part of this 
research study. 
 
Biopsy samples picked up via courier and taken to Annapath Inc for processing 
will be sent coded.  
 
Transmission of eCRF’s from WRNMMC to the Data Coordinating Center 
(DCC) located at the UPMC Center for Innovation in Restorative Medicine 
(CIRM) will be accomplished via use of a web browser to access the Medrio 
data entry system.  The integrity of the data is paramount.  The Medrio system 
is fully 21 CFR Part 11 compliant with the FDA and meets all HIPAA Privacy 
Rule requirements. To ensure data integrity is maintained, the database will be 
held on a secure server, access will be restricted by study role and every data 
entry person will have individualized password access to protected files for 
online data entry, audit trails will be available, all data will be encrypted and 
regularly backed up and secured.  
 
Transmission of coded digital photographs to the DCC will be accomplished by 
mailing the computer disc overnight to the UPMC Center for Innovation in 
Restorative Medicine (CIRM), Department of Plastic Surgery at the University 
of Pittsburgh. .  Transfer of the computer disc containing coded digital 
photographs will occur at the end of the study. The coded digital photographs 
will be stored indefinitely with the study Master Files on the disc on which they 
were received. 
 
The research team in the Department of Orthopaedics and Rehabilitation will 
retain subjects coded PHI and coded photos for up to seven years (as mandated by 
the Sponsor) past completion of the study. Upon completion of the seven year 
storage of documents requirement, all documents will be shredded per 
WRNMMC policy regarding destruction of confidential documents and all 
digital/electronic files will be erased. The master code list which links the 
subjects name and 3-digit study ID number will be destroyed as soon as all data 
collection for this study is completed.  Maintenance of data, coded biopsy results, 
coded digital photographs will be stored indefinitely at the discretion of the 
Principal Investigator for potential educational purposes as well as review and 
analysis. 
 
All research staff at WRNMMC will provide evidence to the sponsor of training 
in research conduct and compliance via completion of all required research 
modules, and education in Good Clinical Practice in research.  Copies of the 
CITI certificates will be utilized for compliance with this aspect of the protocol. 
 
The Laboratory technicians will be well-versed in the risks of their practice and 
thoroughly address the subject prior to each exam and inclusive of the risks of 
venipuncture procedure.  All exams will be terminated should the subject 
expresses any concerns, issues or discomfort. 
 
All aspects of the study will be performed in a private room, including the 

 
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consenting process, exams and in assisting subject with completing 
questionnaires, laboratory blood draw and the ReCell device surgical procedure. 
The collection of sensitive information about subjects is limited to the amount 
necessary to achieve the aims of the research, so that no unneeded sensitive 
information is being collected; drapes or other barriers will be used for subjects 
who are required to disrobe. 
 
d. Certificate of Confidentiality 
Not applicable 
 
6.4 Reporting Adverse Events and Unanticipated Problems 
It is the responsibility of the Investigators to supply the medical documentation 
needed to support the expedited AE reports in a timely manner.  Failure to provide the 
requested information may result in the termination of the study. 
 
Expected adverse events which are not serious are reported on the Continuing 
Review (CR) Progress Report. e CR is generally performed on a 12-month cycle. 
More frequent Progress Reports may be required at the discretion of the IRB. 
 
Serious Adverse Events: The PI, within 24 hours of first learning of the event, must 
report all related or possibly-related AND serious adverse events (SAE) occurring in 
subjects enrolled at WRNMMC.  This is accomplished by submitting an adverse 
event report to the IRB via IRBNet.  For protocols involving investigational drugs or 
devices, the investigator must also report a serious adverse event to the sponsor of 
the IND or IDE immediately (within 24 hours) of learning of the event. Serious 
adverse events must be reported even if the PI believes that the adverse events are 
unrelated to the protocol. 
 
Unexpected (but not serious) adverse events occurring in subjects enrolled at WRNMMC 
which, in the opinion of the PI, are possibly related to participation AND places subjects 
or others at a greater risk of harm that was previously known or recognized in the protocol 
must be reported by the PI within 24 hours of discovery by email or phone to the IRB and 
the Medical Research Monitor.  A follow-up written report within 5 business days to the 
IRB and the Medical Research Monitor through IRBNet is required. 
 
Unanticipated problems involving risks to subjects or others (UPIRTSOs) must be 
reported to the IRB and Medical Research Monitor via email or telephone within 24 
hours of discovery and a written follow up report within 5 business days. 
 
When a protocol deviation and/or violation occurs, the investigator shall report the 
occurrence to the IRB. The investigator is required to make the determination whether 
the deviation and/or violation meets the criteria for an unanticipated problem involving 
risks to subjects or others.  The IRB Chair or IRB staff member shall also make the 
determination if the protocol deviation meets the definition of an unanticipated problem 
involving risks to participants or others.  If the IRB Chair or IRB Staff member 
determines and documents that the deviation is an unanticipated problem involving risks 
to subjects or others or the deviation resulted from serious or continuing 
noncompliance, the IRB staff member shall place the deviation on the agenda of the next 

 
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available IRB meeting for review.  If the IRB Chair or IRB Staff member determines 
and documents that the deviation is not an unanticipated problem involving risks to 
subjects or others, the IRB Chair or staff member shall acknowledge the submission and 
complete the review through an administrative review procedure. 
 
As a reminder, according to DoDI 3216.12 (November 8, 2011), the IRB shall approve an 
independent medical research monitor by name for all DoD-conducted research involving 
human subjects, determined by the IRB to involve more than minimal risk to human 
subjects. Additionally, the medical research monitor may be identified by an investigator 
or appointed by an IRB or IO for research involving human subjects determined to 
involve minimal risk. 
 
The medical research monitor may perform oversight functions and will report their 
observations to the IRB or a designated official.  The medical research monitor may 
discuss the research protocol with the investigators, interview human subjects, and 
consult with others outside of the study about the research.  The medical research 
monitor shall have the authority to stop a research protocol in progress, remove 
individual subjects from a research protocol, and take whatever steps are necessary to 
protect the safety and well-being of human subjects until the IRB can assess the 
monitor’s report. Medical research monitors shall have the responsibility to promptly 
report their observations and findings to the IRB or other designated official. The 
medical research monitors shall have expertise consonant with the nature of risk(s) 
identified within the research protocol, and they shall be independent of the team 
conducting the research involving human subjects. 
 
Reporting Requirements and Responsibilities for the Principal Investigator to the US 
Army Medical Research and Materiel Command (USAMRMC) Office of Research 
Protections (ORP) Human Research Protection Office (HRPO) 
 The standard reporting requirements to HRPO are outlined as follows: 
 
a. The protocol will not be initiated until written notification of approval of the    
research project is issued by the HRPO.  
 
b. For protocols involving multiple research sites and/or multi-institutional   
collaborations on a single study, the HRPO must review and approve site specific 
           documentation prior to participation in human research activities. 
 
c. The Principal Investigator must comply with the following minimum reporting 
requirements. Specific reporting requirements for the protocol will be included in the 
HRPO Approval Memorandum. Failure to comply could result in suspension of 
funding.  
 
(1) Substantive modifications to the research protocol and any modifications that 
could potentially increase risk to subjects must be submitted to the HRPO for 
approval prior to implementation. The USAMRMC ORP HRPO defines a 
substantive modification as a change in Principal Investigator, change or addition of 
an institution, elimination or alteration of the consent process, change to the study 
population that has regulatory implications (e.g. adding children, adding active duty 

 
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population, etc), significant change in study design (i.e. would prompt additional 
scientific review) or a change that could potentially increase risks to subjects.  
 
(2) Any changes of the IRB used to review and approve the research will be 
promptly reported to the USAMRMC ORP HRPO.  
 
(3) All unanticipated problems involving risk to subjects or others must be promptly 
reported by telephone (301-619-2165), by facsimile (301-619-7803) or by email 
(usarmy.detrick.medcom-usamrmc.other.hrpo@mail.mil), to the HRPO. A complete 
written report will follow the initial notification. In addition to the methods above, 
the complete report can be sent to the US Army Medical Research and Materiel 
Command, ATTN: MCMR-RP, 810 Schreider Street, Fort Detrick, Maryland 21702-
5000. 
 
(4) Suspensions, clinical holds (voluntary or involuntary), or terminations of this 
research by the Institutional Review Board (IRB), the institution, the Sponsor, or 
regulatory agencies will be promptly reported to the USAMRMC ORP HRPO. 
 
(5) A copy of the continuing review approval notification by the IRB of Record must 
be submitted to the HRPO as soon as possible after receipt. For greater than minimal 
risk research, a copy of the continuing review report approved by the IRB must also 
be provided. Please note that the HRPO also conducts random audits at the time of 
continuing review. Additional information and documentation may be requested at 
that time. 
 
(6) The final study report, including any acknowledgement documentation and 
supporting documents, must be submitted to the HRPO when available. 
 
(7) The knowledge of any pending compliance inspection/visit by the FDA, DHHS 
Office of Human Research Protections (OHRP), or other government agency 
concerning this research, the issuance of Inspection Reports, FDA Form 483, 
warning letters or actions taken by any regulatory agencies including legal or 
medical actions and any instances of serious or continuing noncompliance with the 
regulations or requirements, must be promptly reported to the HRPO. 
 
The USAMRMC ORP HRPO conducts site visits as part of its responsibility for 
compliance oversight. Accurate and complete study records must be maintained and 
made available to representatives of the USAMRMC as a part of their responsibility to 
protect human subjects in research. Research records must be stored in a confidential 
manner so as to protect the confidentiality of subject information. 
 
7. INVESTIGATOR AGREEMENT 
 
By submitting this protocol and providing an electronic signature in IRBNet, or an ink 
signature below, I agree to the following statements: 
 
General Assurance:  I agree to conduct the study as outlined herein.  I certify that all 
procedures involving human subjects have been described in full. 

 
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Starting the Study:  I understand I cannot begin the study until I have received an 
approval letter documenting approval by the WRNMMC IRB and HRPO. 
 
Consent:  I am responsible for assuring the quality of each subject’s consent in 
accordance with current federal regulations.  This includes ensuring that any 
“designee” that obtains consent on my behalf is completely familiar with the protocol 
and is qualified to perform this responsibility. 
 
Adverse Events:  I understand that I must report research related or possibly research 
related serious adverse events within 24 hours of discovery to the IRB.  If the IRB 
has required a medical research monitor, the medical research monitor will also 
review the relatedness and the serious nature of the adverse event. I will report 
unexpected (but not serious) adverse events that may possibly be related to 
participation in the protocol within 5 working days of their discovery to the IRB 
using the same procedure. 
 
Training:  I verify that the personnel performing these procedures described in this 
protocol are technically competent, have been properly trained, and are appropriately 
qualified. 
 
Compensation:  I am aware that members of the research team are not authorized to 
accept any form of personal compensation for our efforts in conducting this research. 
 
Modifications:  I am aware that all changes to the protocol must be approved by the IRB 
before implementation.  Examples of changes to protocols that require IRB approval 
include, but are not limited to, change of on-site PI, addition of personnel on study, 
increased sample size, addition of other data points, sources of outside funding, addition 
of data collection sites, and changes in the data requested or the purpose of the data use. 
 
Deviations to the Protocol:  I am aware that any protocol deviations discovered by 
either the PI or auditing official will be immediately reported to the IRB.  All corrective 
actions will be documented and become a part of the master study file, along with the 
report. 
 
Duplication of Effort:  I have made a reasonable good faith effort to ensure that this 
protocol is not an unnecessary duplication of previous experiments. 
 
Reports:  I agree to provide a Continuing Review Progress Report 30 days prior to the 
anniversary of the protocol’s initial approval or as stipulated by the IRB.  I agree to 
submit a final report within 30 days following closure, completion or termination of the 
study. 
 
Maintain Study Files: I agree to maintain a Study File that must be kept for three years 
from the date the study is closed (32 CFR 219.115(b) consent and that HIPAA 
authorizations will be retained for 6 years after the study is closed and provided to 
WRNMMC upon request.  If IND medication or IDE appliances are used, the file must 
be kept for 2 years after FDA approval and can then be destroyed; or if no application is 

 
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filed or approved, until 2 years after the study is discontinued and the FDA notified 
(21CFR 312.62(c)).  However, per Sponsor request, study files, eCRF’s, consent and 
HIPAA authorizations will be retained for 7 years after study completion. I acknowledge 
that research data are the property of the Command and will not be removed without 
prior approval. When I am scheduled to permanent change of station (PCS) or end of 
time in service (ETS), study records will be given to a new PI, the Department Chief. 
 
This file may be inspected at any time by Department of Research Programs, DoD 
oversight entities, the FDA, and/or other applicable regulatory agencies responsible for 
the oversight of research.  This file will include: 
 
A. The approved protocol and applicable amendments. 
B. The IRB minutes granting approval to initiate the study. 
C. IRB approval letter. 
D. Each Consent Form and HIPAA Authorization signed by the subject or 
Legally Authorized Representative (LAR). 
E. HIPAA documentation required to meet regulatory compliance, 
F. Continuing Review Progress Reports and Reports related to modifications. 
G. Reports of adverse effects. 
H. Reports of any significant new findings found during the course of the study. 
I. All study documents generated from study date. 
J. Publications, abstracts, and reprints resulting from study data. 
K. All information pertaining to an investigational drug or device. 
 
Publications:  I am aware that advertisements, abstracts, presentations or publications 
resulting from research protocols must have their products cleared by the Public Affairs 
Office, undergo Operation Security (OPSEC) review, undergo review for release of 
actionable medical information, and publication clearance. 
 
HIPAA Compliance: I will provide each research participant with a copy of their 
signed and dated HIPAA Authorization and will immediately notify the IRB Privacy 
Board when a research participant revokes his/her signed Authorization, and I will no 
longer seek to obtain PHI pertaining to that individual for this research project, or any 
other purpose absent a separate authorization or appropriate waiver. 
 
Applicable Regulations:  I am familiar with applicable regulations governing 
research, and will adhere to all of the requirements outlined in the DoD Assurance for 
the WRNMMC. 
 
I understand that if I fail to comply with any of these responsibilities, all projects for 
which I am an investigator may be suspended. 
 
LTC Leon J. Nesti, MC, USA 
Hand and Upper Extremity Reconstructive Surgeon 
Department of Orthopedics, 
Walter Reed National Military Medical Center 
8901 Wisconsin Ave 
Bethesda, MD 20889 

 
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Phone: (240) 994-7347 
E-mail: Leon.J.Nesti.mil@mail.mil 
 
(Electronic signature in IRBNet is provided) 
8.LEADERSHIP ACKNOWLEDGEMENT 
 
I concur with the submission of this proposal to the Department of Research 
Programs for review and approval. 
 
DEPARTMENT CHIEF 
CDR David E. Gwinn, MC, USN 
Department Chief of Orthopaedics 
Department of Orthopaedics, WRNMMC 
 
LCDR Scott M. Tintle, MC, USN 
Research Director  
Department of Orthopaedics, WRNMMC 
   
(Electronic signature in IRBNet is provided) 
9. REFERENCES 
 
Belmont, P.J., A.J. Schoenfeld, and G. Goodman, Epidemiology of combat wounds in 
Operation Iraqi Freedom and Operation Enduring Freedom: orthopaedic burden of 
disease. Journal of surgical orthopaedic advances, 2010. 19(1): p. 2-7. 
 
Bumbasirevic, M., et al., Treatment of blast injuries of the extremity. J Am Acad 
OrthopSurg, 2006. 14(10 Spec No.): p. S77-81. 
Covey, D.C., et al., Orthopaedic war injuries: from combat casualty care to definitive 
treatment: a current review of clinical advances, basic science, and research 
opportunities. Instructional course lectures, 2008. 57: p. 65-86. 
 
Cernak, I., et al., Blast injury from explosive munitions. The Journal of trauma, 1999. 
47(1): p. 96-103; discussion 103-4. 
 
Conti E, Wood F, Leclerc-Chalvet M. ReCell®: Indications, Clinical practice and 
Expected outcome. Journal of Wound Technology. April 2009(4):59-62. 
 
Deitch EA, Wheelahan TM, Rose MP, Clothier J, Cotter J. Hypertrophic burn scars: 
analysis of variables. J Trauma. Oct 1983;23(10):895-898. 
 
DoD Personnel & Procurement Reports and Data Files: Military Casualty Information. 
2011; Available from: http://siadapp.dmdc.osd.mil/personnel/CASUALTY/castop.htm. 
 
Draaijers LJ, Tempelman FR, Botman YA, et al. The patient and observer scar 
assessment scale: a reliable and feasible tool for scar evaluation. Plastic and 
Reconstructive Surgery. Jun 2004;113(7):1960-1965; discussion 1966-1967. 
 
Drake LA, Dorner W, Goltz RW, et al. Guidelines of care for contact dermatitis. 

 
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Committee on Guidelines of Care. J Am Acad Derm. Jan 1995;32(1):109-113. 
 
Durani P, McGrouther DA, Ferguson MW. Current scales for assessing human scarring: 
a review. Journal of Plastic, Reconstructive & Aesthetic Surgery. Jun 2009;62(6):713- 
720. 
 
Idriss N, Maibach HI. Scar assessment scales: a dermatologic overview. Skin Res 
Technol. Feb 2009;15(1):1-5. 
 
Mabry, R.L., et al., United States Army Rangers in Somalia: an analysis of combat 
casualties on an urban battlefield. The Journal of trauma, 2000. 49(3): p. 515-28; 
discussion 528-9. 
 
Masini, B.D., et al., Resource utilization and disability outcome assessment of combat 
casualties from Operation Iraqi Freedom and Operation Enduring Freedom. Journal of 
orthopaedic trauma, 2009. 23(4): p. 261-6. 
Mazurek, M.T. and J.R. Ficke, The scope of wounds encountered in casualties from the 
global war on terrorism: from the battlefield to the tertiary treatment facility. J Am 
AcadOrthop Surg, 2006. 14(10 Spec No.): p. S18-23. 
 
Moiemen NS, Vlachou E, Staiano JJ, Thawy Y, Frame JD. Reconstructive surgery with 
Integra dermal regeneration template: histologic study, clinical evaluation, and current 
practice. Plastic and Reconstructive Surgery. Jun 2006;117(7):160S-174S. 
 
Noe, A., Extremity injury in war: a brief history. J Am Acad Orthop Surg, 2006. 
14(10Spec No.): p. S1-6. 
 
Owens, B.D., et al., Characterization of extremity wounds in Operation Iraqi Freedom 
and Operation Enduring Freedom. Journal of orthopaedic trauma, 2007. 21(4): p. 254-7. 
 
Starnes, B.W., et al., Extremity vascular injuries on the battlefield: tips for surgeons 
deploying to war. The Journal of trauma, 2006. 60(2): p. 432-42. 
 
U.S. Department of Defense Website. DefenseLINK US Casualty Status. 2011; Available 
from: http://www.defense.gov/news/casualty.pdf. 
 
Wood FM, Giles N, Stevenson A, Rea S, Fear M. Characterisation of the cell suspension 
harvested from the dermal epidermal junction using a ReCell kit. Burns. 2011;in press. 
 
Zouris, J.M., et al., Wounding patterns for U.S. Marines and sailors during Operation 
Iraqi Freedom, major combat phase. Military Medicine, 2006. 171(3): p. 246-52. 
 
10.BUDGET 
Will any outside organization provide funding or other resources? Yes (  x )  No ( 
) 
Please refer to Appendix K 
 
APPENDICES 
Appendix A1 and 2 - Manufacturer’s Instructions for Use (IFU) for the Autologous Cell 

 
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Harvesting (ReCell) device and kit Set Up Card 
 
Appendix B - Patient Observer Scar Assessment Scale (POSAS) Questionnaire and 
Copyright 
 
Appendix C - Vancouver Scar Scale 
 
Appendix D - Functional Outcome Rating: Scar Pain Questionnaire 
Appendix E - Subject Satisfaction Questionnaire 
Appendix F - Annapath, Inc Technical Guidelines 
Appendix G - Annapath, Inc Procedure Protocol 
Appendix H - Data Management Plan, including Statistical Management Plan 
 
Appendix I - Clinical Monitoring Plan  
 
Appendix J - Schematic 
 
Appendix K - Budget 
 
Appendix L – Sample electronic Case Report Forms (eCRF) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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Procedure 
 
Screen
ing/ 
Pre-
Treat
ment 
 
 
OR 
Assessments  for Safety Tolerability 
and Preliminary Effectiveness 
Assessments for 
Safety, Aesthetic, & 
Functional 
Outcomes 
Wee
k1 
Wee
k2 
Wee
k3 
Wee
k4 
Wee
k6 
Week 
12 
Week 
24 
Visit Window Interval 
-30 
Days 
 
±3 
days 
±2 
days 
±2 
days 
±2 
days 
±2 
days 
±14 
days 
±14 
days 
Informed 
Consent/Enrollment 
X 
 
 
 
 
 
 
 
 
Medical Historya  
X 
 
 
 
 
 
 
 
 
Demographicsb 
 
X 
 
 
 
 
 
 
 
 
Physical Examination 
X 
 
 
 
 
 
 
 
 
Vital Signsc 
X 
 
X 
X 
X 
X 
X 
X 
X 
Injury Assessment of 
area treated with   
INTEGRA™ 
MBWMd  
X 
 
 
 
 
 
 
 
 
Pain and Pruritus 
(baseline eval) 
X 
 
 
 
 
 
 
 
 
Hematology/Chemistr
ye 
X 
 
X 
 
 
 
 
 
 
Radiographic 
Imagingf 
X 
 
 
 
 
 
 
 
X 
Verification of 
Eligibility Criteriag 
X 
 
 
 
 
 
 
 
 
Randomizationh 
 
X 
 
 
 
 
 
 
 
Histologyi 
 
X 
 
X 
 
X 
 
X 
 
Digital Photographyj 
 
X 
X 
X 
X 
X 
X 
X 
X 
Donor Site Tissue 
Harvestingk 
 
X 
 
 
 
 
 
 
 
Application of 
Investigational 
Product (ReCell 
Procedure) 
 
X 
 
 
 
 
 
 
 
Wound & Donor Site 
Healing Assessmentsl 
 
 
X 
X 
X 
X 
X 
X 
 
POSASm 
 
 
X 
X 
X 
X 
X 
X 
X 

 
Page 76 of 76 
Dermal Protocol Version 4, 04 SEP 15 
 
 
a) 
Current medication use and allergies 
b) 
Date of birth, gender, race/ethnicity 
c) 
Oral temperature, heart rate, respiration rate and blood pressure 
d) 
Assessment to determine if traumatic wound is fully engrafted as indicated by formation of a viable granulation layer 
e) 
Complete blood count (CBC) with differential panel coagulation studies to include prothrombin time (PT) and international 
normalized ratio (INR) and comprehensive metabolic panel (CMP) 
f) 
Radiographic imaging (anterior/posterior and lateral films) for assessment of heterotopic ossification (presence/absence) pre-
treatment/baseline if not previously obtained within 30 days of study enrollment and at Week 24 post-treatment 
g) 
Verification of eligibility will be performed at Screening and Re-verification of eligibility just prior to picking up 
investigational device from pharmacy 
h) 
Wound site will be labeled as “A” region and “B” region PRIOR to opening randomization envelope 
i) 
Pre-treatment (baseline) biopsies at Integra area and of adjacent normal skin; then at Weeks 2, 4, 12 post-treatment, biopsies 
will be taken from the Recell and Control treated sites.   
j) 
Photos will be taken at following time points: PRE-TREATMENT- Control and ReCell sites (“A” region and “B” region); 
Donor sites (ReCell, 1:1.5 and 1:5 meshing) following tissue removal, at treatment wound area prior to primary dressing 
placement and of the ReCell donor site, control area and ReCell treated area at each post-treatment visit for assessment of 
healing process 
k) 
ReCell donor tissue harvested for cell suspension; donor tissue harvested for STSG Control area (meshed at 1:1.5) and donor 
tissue for the ReCell treatment area (meshed at 1:5 mesh) 
l) 
Assessments made for: Atypical healing and/or delayed healing/non-healing, graft loss, heterotopic ossification, infection scar 
contracture, durability (i.e. abrasions/injuries at graft site due to fragility), allergic response to trypsin 
m) 
Subject to complete “patient” part of POSAS at all post-treatment study visits. Full POSAS (including patient and two 
independent observers) completed at Week 12 and 24 post-treatment  
n) 
Concomitant medication use (excluding anesthetic regimen) and all treatment regimens applied in the management of 
infection during the acute healing phase  
o) 
AEs assessed from time of enrollment through study completion (Week 24) including AEs related to treatment requiring 
surgical intervention prior to Week 12 post-treatment and all serious adverse event occurrences 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Vancouver Scar Scale 
(VSS) 
 
 
 
 
 
 
 
X 
X 
Functional Outcome 
Rating 
 
 
 
 
 
 
 
X 
X 
Patient Satisfaction 
 
 
 
 
 
 
 
X 
X 
Concomitant 
Medicationsn 
X 
 
X 
X 
X 
X 
X 
X 
X 
Adverse Eventso 
X 
X 
X 
X 
X 
X 
X 
X 
X