Meso BioMatrix Acellular Peritoneum Matrix Breast Reconstruction Feasibility Trial
Phase: NA
Conditions: Breast Cancer
Sponsor: Kensey Nash Corporation

 
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Meso BioMatrix™ Acellular Peritoneum Matrix 
Breast Reconstruction Feasibility Trial  
Protocol 
 
Protocol Number 
MESO-001 
 
IDE Number 
G120040 
 
Clinicaltrials.gov Registration Number 
NCT01823107 
 
Sponsor 
DSM Biomedical 
Exton, PA USA 
 
Version Number 
Version 6 
 
Version Date 
April 4, 2014 
 
Protocol Approval 
 
____________________________________  
 
_____________________ 
Forde Hansell, Sr. Manager of Clinical Research  
 
 
Date 
DSM Biomedical 
 
 
Protocol Acceptance 
 
____________________________________  
 
_____________________ 
Investigational Site Principal Investigator 
 
 
 
Date 
 
 
CONFIDENTIAL

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Table of Contents 
1. 
PROTOCOL SUMMARY .................................................................................................................................... 4 
2. 
TRIAL TITLE ................................................................................................................................................... 5 
3. 
INVESTIGATIONAL DEVICE ............................................................................................................................. 5 
3.1. 
Meso BioMatrix™ Implant ................................................................................................................. 5 
3.2. 
Regulatory History of Device .............................................................................................................. 5 
3.3. 
510(k) Cleared Indication.................................................................................................................... 5 
3.4. 
Clinical Investigation Intended Use .................................................................................................... 5 
3.5. 
Description of Device ........................................................................................................................... 5 
4. 
BACKGROUND INFORMATION ......................................................................................................................... 5 
4.1. 
Two-stage, Tissue Expander Assisted Breast Reconstruction ............................................................ 5 
4.2. 
Relevant Systematic Literature Reviews............................................................................................. 6 
4.3. 
Preclinical Testing ............................................................................................................................... 7 
4.4. 
Justification for the Trial .................................................................................................................... 7 
5. 
TRIAL INTRODUCTION .................................................................................................................................... 7 
5.1. 
Trial Design ......................................................................................................................................... 7 
5.2. 
Primary Trial Hypothesis.................................................................................................................... 7 
5.3. 
Purpose ................................................................................................................................................ 7 
5.4. 
Trial Objectives ................................................................................................................................... 8 
5.5. 
Primary Endpoint ............................................................................................................................... 8 
5.6. 
Secondary Endpoints........................................................................................................................... 8 
5.7. 
Follow-Up Duration ............................................................................................................................ 8 
5.8. 
Endpoint Evaluation Criteria ............................................................................................................. 8 
5.9. 
Number of Subjects to be Enrolled ..................................................................................................... 9 
5.10. Participating Clinical Sites .................................................................................................................. 9 
5.11. Control Population .............................................................................................................................. 9 
5.12. Minimization of Bias ........................................................................................................................... 9 
5.13. Duration of the Investigation .............................................................................................................. 9 
6. 
SUBJECT POPULATION .................................................................................................................................... 9 
6.1. 
Subject Selection-Criteria for Inclusion.............................................................................................. 9 
6.2. 
Subject Selection-Criteria for Exclusion ........................................................................................... 10 
7. 
TRIAL PROCEDURES, TESTS AND TREATMENTS ............................................................................................ 10 
7.1. 
Informed Consent Requirements ...................................................................................................... 10 
7.2. 
Subject Enrollment............................................................................................................................ 10 
7.3. 
Surgical Procedure Descriptions ....................................................................................................... 10 
7.4. 
Trial Medication ................................................................................................................................ 12 
7.5. 
Required Tests and Evaluations........................................................................................................ 12 
7.6. 
Schedule of Trial Required Visits and Visit Requirements .............................................................. 13 
7.7. 
Adjunctive Aesthetic Procedures ...................................................................................................... 14 
7.8. 
Unplanned Surgical Procedures ........................................................................................................ 14 
7.9. 
Reimbursement for Time and Travel ............................................................................................... 14 
8. 
TRIAL DEFINITIONS ...................................................................................................................................... 15 
9. 
RISK ANALYSIS ............................................................................................................................................. 17 
9.1. 
General Risks Associated with Surgery ............................................................................................ 17 

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9.2. 
Risks Associated with Tissue Expanders .......................................................................................... 17 
9.3. 
Risks Associated with Breast Implants ............................................................................................. 18 
9.4. 
Risks Associated with Biologic Surgical Mesh .................................................................................. 19 
9.5. 
Risk Associated with Tissue Biopsy .................................................................................................. 19 
9.6. 
Risk Mitigation .................................................................................................................................. 19 
9.7. 
Anticipated Clinical Benefits ............................................................................................................. 20 
9.8. 
Alternative Treatments ..................................................................................................................... 20 
10. TRIAL DATA COLLECTION, MONITORING AND QUALITY MANAGEMENT ..................................................... 20 
10.1. Data Management ............................................................................................................................. 20 
10.2. Clinical Site Initiation ....................................................................................................................... 21 
10.3. Trial Data Monitoring ....................................................................................................................... 21 
10.4. Clinical Site Closeout ........................................................................................................................ 21 
11. STATISTICAL CONSIDERATIONS .................................................................................................................... 21 
11.1. Sample Size Justification ................................................................................................................... 21 
11.2. Statistical Analysis............................................................................................................................. 21 
11.3. Interim Analysis Plans ...................................................................................................................... 21 
11.4. Criteria for Trial Termination .......................................................................................................... 21 
12. TRIAL ADMINISTRATION .............................................................................................................................. 22 
12.1. Trial Principal Investigator............................................................................................................... 22 
12.2. Sponsor .............................................................................................................................................. 22 
12.3. Trial Monitor..................................................................................................................................... 23 
12.4. Data Management ............................................................................................................................. 23 
12.5. Core Laboratory................................................................................................................................ 23 
13. ADVERSE EVENT REPORTING .............................................................................................................. 23 
13.1. Adverse Events .................................................................................................................................. 23 
13.2. Serious Adverse Events ..................................................................................................................... 24 
13.3. Unanticipated Adverse Device Effects .............................................................................................. 24 
14. TRIAL RESPONSIBILITIES .............................................................................................................................. 24 
14.1. General Responsibilities .................................................................................................................... 24 
14.2. Investigator Responsibilities ............................................................................................................. 24 
14.3. Sponsor Responsibilities .................................................................................................................... 25 
14.4. Monitor Responsibilities.................................................................................................................... 26 
15. PUBLICATION POLICY ................................................................................................................................... 27 
16. REFERENCES................................................................................................................................................. 27 
 

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1. PROTOCOL SUMMARY 
Title: Meso BioMatrix Breast Reconstruction Feasibility Trial 
Investigational Device Description: The Meso BioMatrix™ Acellular Peritoneum Matrix (“Meso 
BioMatrix) is a bioresorbable porcine mesothelium-derived surgical mesh intended for reinforcement of 
soft tissues. The device is supplied sterile in double-layer packages.  Meso BioMatrix is replaced by host 
tissue during the healing process. 
Clinical Investigation Intended Use: The Meso BioMatrix implant is intended for implantation to 
reinforce soft tissues where weakness exists in subjects requiring soft tissue repair and/or reinforcement 
during breast reconstruction surgery. 
Design: Prospective, multi-center, single-arm, feasibility phase trial.  
Purpose: Demonstrate the feasibility and initial safety of the Meso BioMatrix for the reinforcement of 
weak soft tissue during two-stage, tissue expander-assisted breast reconstruction. 
Primary Hypothesis: Meso BioMatrix can be safely used to provide reinforcement for the weak inferior 
mastectomy skin flaps during two-stage, tissue expander-assisted breast reconstruction.    
Enrollment: A total of 25 subjects. 
Clinical Sites: 10 clinical sites in the United States will participate. 
Subject Population: Subjects undergoing two-stage, tissue expander-assisted breast reconstruction 
meeting eligibility criteria. 
Follow-up Visits:  
x 
Office  visits  at  1  week  and  2  weeks  after  Meso  BioMatrix  implantation  followed  by  every  1  –  4  
weeks for tissue expansion.   
x 
Office visits at 1 week, 1 month, 3 months, 6 months and 12 months after the tissue expander is 
exchanged for a permanent breast implant. 
Primary Endpoint: Rate of breast related adverse events throughout the follow-up period.   
Secondary Endpoints:  
x 
Rate of all serious adverse events throughout the follow-up period. 
x 
Presence of host tissue integration into the Meso BioMatrix mesh at the time of tissue expander / 
implant exchange. 
x 
Breast-Q™ Satisfaction with Breast score at the last follow-up visit. 
Principal Investigator:  
To be determined 
Sponsor: 
 
DSM Biomedical 
735 Pennsylvania Drive 
Exton, PA 19341 
 

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2. TRIAL TITLE 
Meso BioMatrix Breast Reconstruction Feasibility Trial 
3. INVESTIGATIONAL DEVICE 
3.1. 
Meso BioMatrix™ Implant 
The device under investigation is the Meso BioMatrix™ Acellular Peritoneum Matrix (“Meso 
BioMatrix”) 
3.2. 
Regulatory History of Device 
The United States Food & Drug Administration (“FDA”) cleared Meso BioMatrix for marketing 
via the 510(k) clearance pathway in May 2010 (K094061).   
3.3. 
510(k) Cleared Indication 
Meso BioMatrix™ is intended for implantation to reinforce soft tissues where weakness exists in 
subjects requiring soft tissue repair, reinforcement in plastic and reconstructive surgery, and in 
the urological, gynecological, and gastroenterological anatomy including but not limited to the 
following procedures: reinforcement of primary closure such as suture line reinforcement and 
muscle flap reinforcement; hernia repair (e.g., hiatal, femoral, paracolostomy, umbilical), urethral 
and vaginal prolapse repair, colon and rectal prolapse repair, reconstruction of the pelvic floor, 
bladder support, and sacrocolposuspension. 
3.4. 
Clinical Investigation Intended Use  
The  Meso  BioMatrix™ implant  is  intended  for  implantation  to  reinforce  soft  tissues  where  
weakness exists in subjects requiring soft tissue repair and/or reinforcement during breast 
reconstruction surgery. 
3.5. 
Description of Device 
The Meso BioMatrix™ implant is a resorbable surgical mesh intended to reinforce soft tissue 
where weakness exists. The implant is derived from porcine peritoneum and is supplied sterile in 
double layer packages. The implant is packaged dry and prior to use is hydrated with saline or 
autologous body fluids such as blood, bone marrow aspirate, or blood concentrates such as 
platelet rich plasma.  Meso BioMatrix provides structural and mechanical support to weak soft 
tissue during the healing process.  Meso BioMatrix is fully replaced with native tissue between 6 
and 12 months. 
4. BACKGROUND INFORMATION 
4.1. 
Two-stage, Tissue Expander Assisted Breast Reconstruction 
Following mastectomy, women may elect to have breast reconstruction with autologous tissue or 
breast implants.  Two-stage, tissue expander assisted breast reconstruction is one of the common 
surgical methods that could be selected to reconstruct the breast.  This method either begins 
immediately after the general surgeon completes the mastectomy (immediate breast 
reconstruction) or at some time afterward (delayed breast reconstruction).  During the first stage 
of the breast reconstruction procedure, the plastic surgeon releases the pectoralis muscle from the 
chest wall in order to create a pocket for the prosthesis.  Then, a tissue expander is implanted 
beneath the pectoralis muscle and partially inflated.  The tissue expander is gradually filled with 
saline over several weeks or months.  Once the desired breast volume has been achieved, the 
second stage of the reconstruction takes place.  In the second stage, the tissue expander is 
removed and replaced with a permanent saline or silicone gel breast implant.  Historically, 
surgeons placed the tissue expander and breast implant either completely or partially under the 
pectoralis muscle.  However, these methods of breast reconstruction have been associated with 

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less favorable aesthetic outcomes1,2.  Therefore, in the early 2000s, surgeons started using 
AlloDerm® Regenerative Tissue Matrix (LifeCell Corporation, Branchburg, NJ), an acellular 
dermal matrix derived from human cadaveric tissue, to reinforce the inferior mastectomy skin 
flap and attempt to improve aesthetic outcomes3.  Use of AlloDerm to reinforce the inferior 
mastectomy skin flap gives surgeons better control of the lower pole of the breast during 
reconstruction and has been associated with less pain, fewer tissue expansions and improved 
aesthetic outcomes3-9.   However,  AlloDerm  adds  significant  cost  to  the  procedure  and  some  
surgeons have seen an increased rate of post-operative complications such as infection, seroma, 
and hematoma when using AlloDerm10-13, while others have seen no significant difference in the 
rate of complications with and without AlloDerm in tissue expander-assisted breast 
reconstruction14,15.  It has been suggested that these increased risks may be related to the surgical 
technique learning curve11, foreign body reaction or the fact that AlloDerm is considered aseptic 
but not sterile13.   
AlloDerm is regulated by the FDA according to the U.S. Code of Federal Regulations, Title 21, 
Part 1270 - Human Tissue Intended for Transplantation and Part 1271 - Human Cells, Tissues, 
and Cellular and Tissue-based Products.  AlloDerm is indicated for repair or replacement of 
damaged or inadequate integumental tissue or for other homologous uses of human integument.  
Therefore, use of AlloDerm in breast reconstruction could be considered an off-label use.  At 
present, there are no biologic surgical mesh devices approved or cleared by the FDA for use in 
breast reconstruction.   
4.2. 
Relevant Systematic Literature Reviews 
Three recent systematic literature review articles were published regarding the use of acellular 
dermal matrices (“ADM”) during breast reconstruction.  Jansen et al. tabulated adverse events 
from 14 relevant articles presenting outcomes after use of AlloDerm16.  Newman et al. tabulated 
adverse events from 12 relevant articles reporting outcomes after use of AlloDerm.  It should be 
noted that 3 of those 12 articles included 3 other biologic mesh devices along with AlloDerm17.  
Hoppe et al. tabulated adverse events from 7 relevant articles comparing outcomes with and 
without the use of AlloDerm during breast reconstruction13.   The adverse events tabulated in 
their systematic reviews are compared in Table 1.    
Table 1: Adverse Events Listed Systematic Review Articles for Breast Reconstruction 
Adverse Event Term 
Jansen et al.*
(AlloDerm only) 
Newman et al.
(ADM) 
Hoppe et al.
(AlloDerm only) 
Breast Reconstruction 
# of Implants = 655 
# of Implants = 789 
# of Implants = 977 
Infection
0 - 11% 
5.2% 
7.6%
Seroma
0 - 9% 
6.0% 
9.4%
Necrosis
0 - 25% 
9.4% 
Not reported
Hematoma
0 - 6.7% 
Not reported 
1.4% 
Exposure w/ Prosthesis Loss
0 - 14% 
Not reported 
Not reported
Exposure w/ Prosthesis 
Salvage 
0 - 4% 
Not reported 
Not reported 
Capsular Contracture
0 - 8% 
Not reported 
Not reported
* Only probability ranges were presented due to limitations in underlying data 
Jansen et al. and Hoppe et al. compared the rates of AlloDerm associated adverse events to 
adverse events in breast reconstruction without a biologic mesh.  Jansen et al. found comparable 
rates of adverse events when a biologic mesh is used for breast surgery versus no biologic mesh 
use.  However, Hoppe et al. found higher rates of adverse events when AlloDerm is used, but 
concluded that AlloDerm use may lead to greater patient satisfaction.  It is important to note that 
the majority of articles in the above systematic review articles were retrospective, single-center 

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experiences.  Such articles are prone to bias since adverse events are usually not uniformly 
defined and documented.  Therefore, the true incidence of complications may have been 
underreported in the studies included in the above systematic reviews.   
The potential benefits to AlloDerm assisted breast reconstruction cited in these systematic review 
articles are: 
x 
Increased initial tissue expander fill volume13 
x 
Reduced operative time13  
x 
Reduced time to full expansion13,16,17 
x 
Reduced time from tissue expander to breast implant exchange16 
x 
Reduced post-operative and tissue expansion pain13,16 
x 
Improved aesthetic outcome16,17 
x 
Less capsular contracture16 
The aforementioned authors all concluded that the potential benefits, when balanced with the 
potential complications, warrant additional study of the use of biologic surgical mesh for breast 
reconstruction.   
4.3. 
Preclinical Testing 
In-vitro  bench  tests  and  in-vivo  animal  studies  have  been  performed  to  assess  the  safety  and  
effectiveness of Meso BioMatrix for soft tissue repair and reinforcement.  The pre-clinical testing 
demonstrated that the device is biocompatible and is replaced by native tissue during the healing 
process.  A summary of the pre-clinical testing can be found in the Report of Prior Investigations 
in the Investigational Device Exemption (“IDE”) application.  The Report of Prior Investigations 
will be provided separately to the investigational sites along with the Investigational Plan. 
4.4. 
Justification for the Trial 
There exists a clinical need for a bioresorbable surgical mesh to support the lower pole of the 
breast during breast reconstruction.  The ideal bioresorbable surgical mesh should be associated 
with a low rate of complications and a high rate of aesthetic success, while being cost effective to 
the subject and healthcare system.  DSM Biomedical has developed a sterile bioresorbable 
surgical mesh with mechanical and handling properties similar to AlloDerm.  This product may 
provide similar benefits as those associated with the use of AlloDerm during breast reconstruction 
and may reduce the risk of post-operative complications associated with AlloDerm.   Therefore, a 
well-designed feasibility trial is warranted to evaluate the feasibility and initial safety of the use 
of Meso BioMatrix during breast reconstruction. 
5. TRIAL INTRODUCTION 
5.1. 
Trial Design 
The trial is designed as a prospective, multi-center, single-arm, feasibility phase trial of subjects 
undergoing two-stage, tissue expander-assisted breast reconstruction.  
5.2. 
Primary Trial Hypothesis 
Meso BioMatrix can be safely used to provide reinforcement for the weak inferior mastectomy 
skin flaps during two-stage, tissue expander-assisted breast reconstruction.    
5.3. 
Purpose 
The purpose of the trial is to demonstrate the feasibility and initial safety of the Meso BioMatrix 
for the reinforcement of weak soft tissue during two-stage, tissue expander-assisted breast 
reconstruction. 

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5.4. 
Trial Objectives 
The primary objective of this trial is to demonstrate the feasibility and initial safety of the Meso 
BioMatrix  when  use  during  breast  reconstruction.   If  successful,  the  data  collected  in  the  
feasibility phase trial may be used to support an IDE supplement for a pivotal phase trial.   
5.5. 
Primary Endpoint  
The primary endpoint of this feasibility phase trial is the rate of post-operative breast related 
adverse events through 12 months after the second stage of the breast reconstruction.   
5.5.1. Primary Endpoint Justification 
The primary endpoint of breast related adverse events provides an objective means to assess the 
initial safety of the Meso BioMatrix implant when used during breast reconstruction.   
5.6. 
Secondary Endpoints  
The secondary endpoints that will be evaluated in this trial are: 
x 
Rate of all serious adverse events after Meso BioMatrix implantation through 12 months after 
the second stage of the reconstruction; 
x 
Presence of host tissue integration into the Meso BioMatrix mesh at the time of second stage 
of the breast reconstruction; 
x 
Breast-Q Satisfaction with Breast score at the final post-operative trial visit. 
5.7. 
Follow-Up Duration 
Subjects enrolled in this trial will have trial required follow-up visits through 12 months after the 
second stage of the breast reconstruction.  It is estimated that the second stage of the 
reconstruction will occur between 3 to 6 months after the first stage.  Therefore, each subject will 
be followed for approximately 15 to 18 months after Meso BioMatrix implantation, which is 
approximately two times the duration of Meso BioMatrix bioresorption.  The follow-up visits are 
to occur according to the follow-up schedule described in Section 7.6 of this protocol.   
5.8. 
Endpoint Evaluation Criteria 
5.8.1. Primary Endpoint Evaluation 
At each operative and post-operative visit, Investigators will document the presence or absence of 
breast related adverse events occurring since the prior visit.  All breast related adverse events 
documented during trial-required visits will be recorded on the trial case report form.  When one 
or more breast related adverse events are reported at one or more of the follow-up visits for an 
individual subject, the occurrence of the primary endpoint will be documented for that subject.   
5.8.2. Secondary Endpoint Determination 
The occurrence of each of the secondary endpoints will be determined as follows: 
x 
At each visit, starting with the Meso BioMatrix implantation visit, Investigators will 
document the presence or absence of serious adverse events.   All serious adverse events will 
be recorded on the trial case report form.  When a serious adverse event is recorded at one or 
more follow-up visits for an individual subject, the occurrence of this secondary endpoint will 
be documented for the subject.   
x 
During the second stage of the breast reconstruction, the tissue expander is surgically 
removed and replaced with a permanent breast implant.  This second surgery provides the 
Investigator with an opportunity to visually inspect the condition Meso BioMatrix implant 
and take biopsies to assess the type and degree of host tissue integration within the implant.  
The biopsies taken during the second stage of the reconstruction will be preserved and sent to 
a central core laboratory for standardized analysis.  If host tissue is found within an individual 
subject’s biopsy specimen, than the occurrence of this secondary endpoint will be 
documented for the subject.   

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x 
At the 6 and 12-month visits after the second stage of the breast reconstruction, subjects will 
complete the Breast-Q Satisfaction with Breast survey.  Each Breast-Q survey will be scored 
according to the author’s instructions.  Descriptive statistics will be presented for the Breast-
Q Satisfaction with Breast scores at 6 and 12 month after the second stage of the 
reconstruction. 
5.9. 
Number of Subjects to be Enrolled 
A total of 25 subjects will be enrolled in this trial.  The maximum allowable enrollment by a 
single clinical investigator is 15 subjects.   
5.10. 
Participating Clinical Sites 
5.10.1. Number of clinical sites 
Ten (10) clinical sites will participate in the trial.   
5.10.2. Investigator Names and Contact Information 
The names, addresses and professional positions of each clinical site Principal Investigator as 
well as the name and address of each Institutional Review Board (IRB) Chairman for each site at 
which the investigation will be conducted is included in Section 8 of the Investigational Plan.   
5.10.3. Investigator Training and Experience Requirements  
All Investigators are board-certified plastic surgeons experienced in two-stage, tissue expander-
assisted breast reconstruction surgery.  All Investigators will receive “hands-on” training on the 
Meso BioMatrix implant prior to their first use.     
5.11. 
Control Population 
As this trial is designed to assess the feasibility as well as the initial safety of Meso BioMatrix 
during breast reconstruction, no control arm population is planned.   
5.12. 
Minimization of Bias 
As this is a single arm feasibility trial of a surgically implanted device, subject and surgeon 
investigator blinding is not possible.  However, bias will be minimized by the following methods: 
x 
A validated subjective patient reported outcome instrument is being used to assess aesthetic 
outcome.   
x 
An independent core laboratory will conduct standardized evaluation of the biopsy 
specimens.   
x 
Subjects will be screened and enrolled prospectively. 
x 
Standardized definitions of all elements of the primary endpoint are provided to the 
investigators in section 8 of this protocol.   
5.13. 
Duration of the Investigation 
Due to the inclusion and exclusion criteria for this trial, subject enrollment  is expected to be 
difficult.   Therefore,  recruitment  of  25  subjects  at  10  clinical  sites  is  projected  to  last  for  
approximately 24 months.  Subjects will be followed for approximately 15 to 18 months after 
implantation with Meso BioMatrix.  Therefore, the duration of time from the first subject’s 
enrollment to the last subject’s last scheduled follow-up is approximately 42 months.     
6. SUBJECT POPULATION 
6.1. 
Subject Selection-Criteria for Inclusion 
Subjects that meet the following criteria of inclusion for this trial will be eligible to be recruited 
for this trial: 
1. ≥ 21 years of age; 
2. Female gender; 
3. Subject is a non-smoker; 

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4. Subject is undergoing unilateral or bilateral, two-stage, tissue expander-assisted breast 
reconstruction; 
5. Target breast(s) has well vascularized skin flaps;   
6. Subject has a life expectancy greater than 18 months; 
7. Subject agrees to return for the trial required follow-up visits; and 
8. Subject provides written informed consent. 
6.2. 
Subject Selection-Criteria for Exclusion 
Candidates will be excluded from the trial if any of the following conditions apply: 
1. Subject has a body mass index ≥ 35; 
2. Subject had prior reconstructive breast surgery, breast augmentation, mastopexy or reduction 
mammoplasty on the target breast(s); 
3. Subject has known or suspected infection at the surgical site;  
4. Subject has a history of chronic corticosteroid use; 
5. Subject has insulin dependent diabetes mellitus; 
6. Subject has known or suspected disease or disorder putting the subject at a high risk for 
adverse events or procedural failure (e.g. HIV, collagen disease, connective tissue disorder, 
etc.); 
7. Subject requires radical mastectomy; 
8. Subject has a history of radiation therapy to the chest; 
9. Subject’s breast cancer is known to need post-operative treatment with adjuvant radiation 
therapy during the follow up period; 
10. Subject treated with pre-operative induction chemotherapy for her breast cancer.  Note,, 
treatment with neoadjuvant chemotherapy is acceptable if the intent is to decrease localized 
breast tumor burden prior to mastectomy; 
11. Subject has known or suspected metastatic malignancy; 
12. Subject is pregnant or desires to become pregnant within 18 months following breast 
reconstruction; 
13. Subject has known or suspected allergy or intolerance to porcine tissue; 
14. Subject has religious or cultural objection to products of porcine origin; or 
15. Subject is concurrently participating in an investigational drug or device trial that has not 
completed the follow-up period.   
16. Subject’s anatomy is not amenable to two-stage, tissue expander-assisted, breast 
reconstruction with biologic surgical mesh reinforcement in the opinion of the Investigator.   
7. TRIAL PROCEDURES, TESTS AND TREATMENTS 
7.1. 
Informed Consent Requirements 
The Investigator or a member of the research staff must obtain written informed consent from 
each  prospective  research  subject.   The  template  informed  consent  form  for  this  trial  was  
prepared in accordance with the U.S. Code of Federal Regulations, Title 21, Part 50.25: Elements 
of Informed Consent.  The informed consent template is included in section 7 of the 
Investigational Plan.  The informed consent form or a modification of it must have prior written 
approval from each clinical site's Institutional Review Board (“IRB”).  All subjects must sign and 
date the most current IRB approved informed consent form prior to enrollment in the trial.  
Failure to provide informed consent renders a subject ineligible for the trial.   
7.2. 
Subject Enrollment 
Each subject providing informed consent that has passed all inclusion criteria and has no 
exclusion criteria present will be enrolled in the trial.   
7.3. 
Surgical Procedure Descriptions 

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7.3.1. First Stage of the Breast Reconstruction 
Surgeons will follow the Meso BioMatrix Instructions for Use included in Section 6 of the 
Investigational Plan.  The surgical technique is summarized below: 
x 
After mastectomy and confirmed hemostasis, the viability of the skin mastectomy skin flaps 
is assessed by visual inspection or imaging and addressed per standard of care.   
x 
The inferior border of the pectoralis major muscle is elevated off the chest wall with blunt 
dissection and/or electrocautery in order to create a pocket for the tissue expander. 
x 
Meso BioMatrix is hydrated with saline and, if necessary, tailored to the individual 
dimensions of the defect. 
x 
Meso BioMatrix is oriented for implantation with the patterned, basal lamina side facing 
downward toward the tissue expander. 
x 
Inferiorly, Meso BioMatrix is sutured to the chest wall in order to recreate the inframammary 
fold with 2-0 or 3-0 PDS™ II suture (Ethicon, Inc. Somerville, NJ).  An interrupted suture 
pattern with approximately 2 cm between suture bites is recommended.  The suture pattern 
will be recorded on the case report form. 
x 
Superiorly, Meso BioMatrix is sutured to the lower pole of the released pectoralis major 
muscle with 2-0 or 3-0 PDS™ II suture.  A continuous suture pattern is recommended.  The 
suture pattern will be recorded on the case report form. 
x 
A partially inflated, textured tissue expander is placed in the created subpectoral pocket.  
x 
The tissue expander is filled until contact is achieved between the tissue expander and the 
Meso BioMatrix implant without subjecting the mastectomy skin flaps to undue tension. The 
volume will be adjusted if ischemia is noted in the skin flaps.  The final initial fill volume 
will be recorded on the case report form. 
x 
A closed suction drain is placed in the subcutaneous space between the skin and the Meso 
BioMatrix.  The drain shall remain in place until output is less than 30cc in a 24-hour period.  
Placement of a second drain in the axilla or elsewhere in the breast is at the surgeon’s 
discretion.  The drain placement location(s) will be recorded on the case report form. 
x 
Finally, the surgeon will close the surgical wounds according to his/her standard of care. 
x 
Any adverse events or Meso BioMatrix malfunctions occurring during the procedure will be 
recorded on the case report form.  A copy of the operative report will be collected from all 
first stage breast reconstruction procedures. 
Note, if the subject is undergoing bilateral mastectomy and reconstruction, both breast 
reconstructions will be performed in the same fashion.  Meso BioMatrix will be used for both 
breast reconstructions.   
7.3.2. Tissue Expansion Phase 
After the skin incision heals, expansion of the tissue expander begins.  Patients will visit the 
Investigator approximately every 1 – 4 weeks for expansion until the desired expander fill volume 
is achieved.   
7.3.3. Second Stage of the Breast Reconstruction 
The second stage of the breast reconstruction is planned after the tissue expander(s) has reached 
the desired volume.  The events that take place during the second stage of the breast 
reconstruction are summarized below: 
x 
The surgeon will access and remove the tissue expander.  The incision location will be 
recorded on the case report form. 
x 
Biopsies of the Meso BioMatrix are taken from the pectoralis muscle interface, the center of 
the Meso BioMatrix, the inframammary fold interface and posterior to the expander.  
Biopsies will be placed in formalin, labeled and shipped to the Core Laboratory.   
x 
A permanent saline or silicone implant will be placed within the pocket. 

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x 
If necessary, adjustments may be made according to the surgeon’s standard of care in order to 
optimize the ultimate position of the breast implant and cosmetic result.   
x 
The incisions will be closed according to the surgeon’s standard of care.  
Note, if the subject is undergoing bilateral reconstruction, the above events will also take place in 
the opposite breast.  If the subject is having unilateral breast reconstruction, augmentation or 
mastopexy may occur in the opposite breast according to the surgeon’s standard of care.  If the 
subject elected to have nipple reconstruction during the second stage of the breast reconstruction, 
it will be done according to the surgeon’s standard of care.  A copy of the operative report will be 
collected for all second stage breast reconstruction procedures. 
7.4. 
Trial Medication 
Subjects in this trial will receive antibiotic prophylaxis consistent with the standard of care at 
each institution.  The following antibiotic administration protocol is recommended for patients in 
this study: 
x 
Within one hour prior to each surgery, subjects will receive 1 to 2 grams of Cefazolin (e.g. 
Ancef) intravenously18.   
x 
During the first and second stage surgeries, breasts will be irrigated with a triple antibiotic 
solution consisting of 1g of Cefazolin, 80mg of Gentamicin and 50,000 units of Bacitracin 
diluted in 1 liter of saline.   
x 
After each surgery, subjects will take 1 – 2 grams daily of a first generation cephalosporin 
(e.g. cefadroxil, cephalexin) by mouth until the drains are removed, approximately 7 - 10 
days.   
In  case  of  patient  allergy  to  one  or  more  of  the  antibiotics  stated  above  or  when  surgery  is  
performed in an institution with high rates of methicillin-resistant Staphylococcus aureus 
(MRSA), Investigators may substitute appropriate doses of appropriate alternative antibiotics 
(e.g. vancomycin pre-operatively18) for prophylaxis per his/her standard of care.   
The type and frequency of antibiotics given to subjects will be collected on the case report form.   
7.5. 
Required Tests and Evaluations  
All subjects enrolled into this trial will undergo and have documented the below evaluations 
during designated visits.  Table 2 displays the schedule for the study-required visits along with 
the required evaluations at each visit.   
7.5.1. Medical History 
A standard medical history will be documented in the subject’s medical records before the breast 
reconstruction surgery to assess the subject for trial eligibility.     
7.5.2. Biopsies 
During the second stage of the breast reconstruction, four biopsy specimens will be obtained: 
1. From the pectoralis muscle – Meso BioMatrix interface, 
2. From the Meso BioMatrix centrally, 
3. From the Inframammary fold – Meso BioMatrix interface, and 
4. From the capsule posterior to the tissue expander as a control.   
The size, location and method of biopsy collection, the method of specimen preservation and the 
method of specimen shipping will be provided separately by the core laboratory in the Core 
Laboratory Specimen Collection Manual.   
7.5.3. Breast-Q™ 
The Breast-Q is a patient reported outcome instrument that has been validated for patients 
undergoing breast surgery19,20.  The Post-operative Reconstruction Module of the Breast-Q will 
be used for this trial.  Subjects will complete the Post-operative Reconstruction module of the 

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Breast-Q at 6 and 12 months after the second stage of the reconstruction.  The Reconstruction 
module of the Breast-Q is copyright protected.  It will be obtained and distributed to the clinical 
sites on a per patient and per use basis for use in the study.    
7.5.4. Patient Diary 
After the first stage of the breast reconstruction, Investigators or research coordinators will record 
the patient’s post-operative level of pain, operative wound color, bruising, drain output, and pain 
medications taken on a daily basis until hospital discharge.  After hospital discharge, patients will 
record their post-operative level of pain, operative wound appearance, bruising, drain output, pain 
medications taken and general comments (if any) on a daily basis in a patient diary until the 2-
week post-operative visit.  The patient diary will be collected by the Investigators or research 
coordinator at the 2-week post-operative visit.   
7.5.5. Photographs 
Photographs are required to be taken pre-operatively and at the last trial required follow-up visit 
(12 months after the second stage of the breast reconstruction).  The pre-operative and last 
follow-up visit photographs provide visual documentation of the change in breast appearance 
during the trial.  If the Investigator identifies a breast related adverse event during the follow-up 
period, photographs must be taken to document the type, location, and severity.       
7.6. 
Schedule of Trial Required Visits and Visit Requirements 
The required visits and the trial requirements at each visit are listed in Table 2 below. 
Table 2: Schedule of Required Visits and Visit Requirements: 
Required Visits 
Visit Requirements 
Pre-operative 
(Within 60 days pre-operative) 
1. Medical History
2.  Inclusion – Exclusion Criteria Screening 
3.  Photographs 
4.  Informed Consent 
1st Stage of Reconstruction: Tissue Expander 
and Meso BioMatrix Implantation 
1. Skin flap viability assessment 
2.  Adverse Event Assessment 
3. Photographs, only if breast adverse event 
4. Patient Diary given at discharge 
1 Week Post 1st Stage Surgery  
(5 – 12 days) 
1.  Adverse Event Assessment 
2. Photographs, only if breast adverse event 
2 Weeks Post 1st Stage Surgery
(12 – 21 days, not to be combined with 1st post-
op visit) 
1. Adverse Event Assessment
2. Photographs, only if breast adverse event 
3. Collect patient diary 
Tissue Expansion Visits
(start after incision healing, then every 1 -4 
weeks as tolerated until full expansion) 
1. Tissue Expansion
2. Adverse Event Assessment 
3. Photographs, only if breast adverse event 
2nd Stage of Reconstruction: 
Tissue Expander – Implant Exchange 
(expected between 2 - 6 months after 1st stage) 
1.  Meso BioMatrix Biopsies 
2.  Adverse Event Assessment  
3. Photographs, only if breast adverse event 
1 Week Post 2nd Stage Surgery 
(5 – 14 days) 
1.  Adverse Event Assessment 
2. Photographs, only if breast adverse event 
1 Month Post 2nd Stage Surgery 
(23- 44 days) 
1.  Adverse Event Assessment 
2. Photographs, only if breast adverse event 
3 Months Post 2nd Stage Surgery 
(2 – 4 months) 
1.  Adverse Event Assessment 
2. Photographs, only if breast adverse event 
6 Months Post 2nd Stage Surgery 
(5 – 7 months) 
1. Adverse Event Assessment
2. Photographs, only if breast adverse event 
3.  Breast-Q 

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Required Visits 
Visit Requirements 
12 Months Post 2nd Stage Surgery 
(11 – 13 months) 
1. Adverse Event Assessment
2.  Photographs 
3.  Breast-Q 
 
Note, with the exception of obtaining biopsy specimens during the second stage of the 
reconstruction, all evaluations, procedures and follow-up visits for this trial are part of the 
standard of care for patients undergoing two-stage, tissue expander-assisted breast reconstruction. 
7.7. 
Adjunctive Aesthetic Procedures 
Two-stage breast reconstruction involves two separate surgical procedures.  However, for some 
subjects, adjunctive procedures may be planned to optimize the aesthetic outcome following the 
second stage of the breast reconstruction.  For example, in subjects whose mastectomy does not 
spare the nipple, a nipple reconstruction may occur during the second stage of the breast 
reconstruction or may be planned for a later surgical procedure.  Additionally, some subjects may 
opt for adjustments to one or both breasts to optimize symmetry, fullness, etc.  Therefore, one or 
more adjunctive aesthetic surgical procedures may be planned during the follow-up period in 
some subjects.  Information about adjunctive aesthetic procedures to either breast will be 
recorded on the Adjunctive Aesthetic Procedure Form in the case report form.  A copy of the 
operative report will be collected for all adjunctive aesthetic procedures involving the 
reconstructed breast(s).  Adjunctive procedures for aesthetic issues will generally not meet the 
definition of a serious adverse event.  See section 13.2 for the serious adverse event definition. 
7.8. 
Unplanned Surgical Procedures 
If any unplanned surgical procedures occur in the reconstructed breast(s) due to an adverse event 
or malfunction of the breast implant, tissue expander or Meso BioMatrix, the information from 
the unplanned procedures will be recorded on the Unplanned Surgical Procedure Form in the case 
report  form.   A  copy  of  the  operative  report  will  be  collected  for  all  unplanned  surgical  
procedures involving the reconstructed breast(s).  Adverse events or device malfunctions 
requiring a surgical procedure will generally meet the definition of a serious adverse event.  See 
section 13.2 for the serious adverse event definition and reporting requirements.   
7.9. 
Reimbursement for Time and Travel 
Subjects may receive up to $1000.00  as reimbursement for time, travel, and completion of study 
related documentation.  The  payment limits per visit are as follows: 
Protocol Requirement
Payment 
1 Week Post 1st Stage Surgery Visit 
$100 
2 Week Post 1st Stage Surgery Visit and return 
of the Patient Diary 
$200 
1 Week Post 2nd Stage Surgery Visit 
$100 
1 Month Post 2nd Stage Surgery Visit 
$100 
3 Month Post 2nd Stage Surgery Visit 
$100 
6  Month  Post  2nd Stage Surgery Visit and 
completion of the outcome questionnaire 
$200 
12  Month  Post  2nd Stage Surgery Visit and 
completion of the outcome questionnaire 
$200 
If a subject does not attend one of the above follow-up visits or does not complete the study 
documentation when required, then no payment will be made to the subject for that follow-up 
visit.   

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8. TRIAL DEFINITIONS 
Asymmetry 
An uneven appearance in terms of size, shape, or position between the two breasts. 
Breast-related Adverse Events 
Any untoward medical occurrence related to the reconstructed breast.  Adverse events that meet 
this definition include but are not necessarily limited to: 
x 
Infection 
x 
Seroma 
x 
Hematoma 
x 
Tissue necrosis 
x 
Dehiscence 
x 
Red breast syndrome 
x 
Allergic reaction 
x 
Inflammatory response 
x 
Meso BioMatrix failure 
x 
Prosthesis extrusion 
x 
Prosthesis (tissue expander or implant) failure 
x 
Capsular contracture (grade 2-4) 
Capsular Contracture 
Defined as tightening of the tissue capsule around a breast implant.  Capsular contracture is 
categorized according to the Baker capsular contracture grading system below: 
x 
Grade I 
= Breast is normally soft and looks natural 
x 
Grade II 
= Breast is a little firm but looks normal 
x 
Grade III 
= Breast is firm and looks abnormal 
x 
Grade IV 
= Breast is hard, painful, and looks abnormal 
Device Failure 
A device failure is a device malfunction that negatively impacts the treatment while used 
according to the labeling.  For example, tearing of the Meso BioMatrix mesh resulting in an 
adverse event is a malfunction that negatively impacted the treatment.   
Device Malfunction 
 
The device does not meet its performance specifications or otherwise does not perform as 
intended. 
Extrusion (implant or tissue expander) 
 Break down in the skin allowing the implant or tissue expander to appear through the skin.  
Hematoma 
 Collection of blood beneath the skin.  
 

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Induction Chemotherapy 
  
Initial treatment provided to patients who have an advanced stage of cancer usually treated with 
high doses of anticancer drugs (such as cisplatin or methotrexate). This can be for the purpose of 
attempting to cure the cancer entirely, or it might just be a preparation for other extensive surgery.  
Induction chemotherapy is given in cycles. Each cycle is followed by a rest period to help 
patients recover from the side effects of chemotherapy. This type of chemotherapy is mainly 
administered for six to twelve months until a patient achieves a stable state. 
Malposition  
Movement of the implant from the correct or intended position within the breast.  
Mastectomy 
Surgical removal of breast tissue.  For this trial, the types of mastectomy will be categorized as 
follows: 
x 
Nipple-sparing mastectomy: surgical removal of the breast tissues, but sparing the skin, 
nipple, and areola.  
x 
Skin-sparing mastectomy: surgical removal of the breast tissues including the nipple and 
areola, but sparing most of the overlying skin.  
x 
Total mastectomy: surgical removal of the breast including the nipple, areola, and most of the 
overlying skin.  
x 
Modified radical mastectomy: surgical removal of the entire breast as well as the lymphatic 
tissue in the axilla.  
x 
Radical mastectomy: surgical removal of the entire breast as well as the pectoral muscles, 
lymphatic bearing tissue in the axilla, and various other neighboring tissue.  
Neoadjuvant Chemotherapy   
Initial use of chemotherapy in patients with localized cancer in order to decrease the tumor 
burden  prior  to  treatment  by  other  modalities.    A  patient  whose  tumor  can  be  removed  by  
mastectomy, but first receives neoadjuvant chemotherapy to shrink the tumor enough to allow 
breast-conserving surgery, may therefore be eligible for this trial.   
Non-smoker 
A subject who either has: 
x 
Never smoked. 
x 
Smoked less than 100 cigarettes in his/her lifetime and had not smoked within 8 weeks 
prior to surgery. 
x 
Smoked at least 100 cigarettes in his or her lifetime but who had quit smoking ≥ 8 weeks 
prior to surgery. 
Red Breast Syndrome 
Erythema in the reconstructed breast overlying the Meso BioMatrix that appears days to weeks 
after breast reconstruction without pain, elevated skin temperature, induration or elevated white 
blood cell count. 
Severe Acute Inflammatory Response  
An  inflammatory  response  is  protective  response  by  the  body  to  harmful  stimuli.   An  acute  
inflammatory response is characterized by early onset of swelling, redness, heat and pain in the 
area of the harmful stimuli.  Severe acute inflammatory response is characterized by substantial 
elevation of C-reactive protein and erythrocyte sedimentation rate, but white blood cell and 
neutrophil counts near or within normal limits.   Inflammatory response versus infection is 
confirmed by negative microbiologic results from cultures obtained from the affected breast.  A 
severe acute inflammatory response in this trial is an acute inflammatory response that requires 
removal of the investigational device.   

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Skin Necrosis 
Dead skin or tissue. 
Ptosis 
Breast drooping or sagging.  For this trial, the degree of ptosis will be classified according to the 
Regnault classification21 as follows: 
1.  Mild ptosis: When the nipple areola complex is at the inframammary fold level. 
2.  Moderate ptosis: When the nipple areola complex is below the inframammary fold but over 
the lower edge of the breast. 
3.  Severe ptosis: When the nipple areola complex is below the inframammary fold and under 
the lower edge of the breast. 
4. Pseudoptosis: When the nipple areola complex is above the inframammary fold but the whole 
breast tissue is located in the lower breast pole. 
Serious Adverse Event 
An adverse event that: 
x is life threatening; 
x results in permanent impairment of a body function;  
x results in permanent damage to a body structure;  
x necessitates medical or surgical intervention to preclude permanent impairment of a body 
function or permanent damage to a body structure; or 
x results in hospitalization or prolongation of hospitalization. 
Seroma 
A fluid collection in a tissue location. 
Surgical Site Infection  
Erythema at the surgical incision in conjunction with a fever or an elevated white blood cell 
count. 
9. RISK ANALYSIS 
9.1. 
General Risks Associated with Surgery 
The risks associated with surgery are described to subjects in the surgical consent form.  Those 
potential complications are the following:  
x 
Bleeding episodes during or after the procedure, in severe cases blood transfusion may be 
necessary; 
x 
Swelling after the procedure; 
x 
Pain after the procedure; 
x 
Nerve damage causing numbness, tingling, pain and/or weakness in the affected area; 
x 
Local or systemic allergic reactions to medications, surgical instruments, sutures and/or 
topical preparations used for the procedure;  
x 
Venous or arterial thrombosis possibly leading to myocardial infarction, cerebrovascular 
accident or pulmonary embolism; and 
x 
Complications from general anesthesia or surgery, which though very rare, could cause death. 
9.2. 
Risks Associated with Tissue Expanders 
The risks associated with tissue expanders during breast reconstruction are described to subjects 
in the surgical consent form provided separately by the surgeon.  The risks associated with tissue 
expanders are22-24: 
x 
Deflation; 
x 
Tissue damage; 
x 
Infection; 

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x 
Extrusion; 
x 
Hematoma; 
x 
Seroma; 
x 
Capsular contracture; 
x 
Premature explantation; 
x 
Displacement; 
x 
Compression on the bones of the chest wall; 
x 
Pain; 
x 
Dysesthesia (abnormal sensation); 
x 
Distortion;  
x 
Inadequate tissue flap; and 
x 
Inflammatory reaction. 
The occurrence of one or more of the above complications may require medical or surgical 
treatment, including additional surgery or tissue expander removal.  
9.3. 
Risks Associated with Breast Implants 
The risks associated with breast implants are described to subjects in the surgical consent form 
provided separately by the surgeon.  Those complications that occur in ≥ 1% of patients receiving 
breast implants25 are as follows: 
x 
Asymmetry;  
x 
Breast feeding difficulties;  
x 
Breast pain;  
x 
Ptosis; 
x 
Calcification;  
x 
Capsular contracture; 
x 
Chest wall deformity; 
x 
Deflation of the breast implant; 
x 
Delayed wound healing;  
x 
Extrusion; 
x 
Hematoma; 
x 
Iatrogenic injury or damage; 
x 
Implant displacement or malposition; 
x 
Implant palpability; 
x 
Implant visibility; 
x 
Implant wrinkling or rippling;  
x 
Infection;  
x 
Inflammation or irritation;  
x 
Necrosis; 
x 
Nipple or breast changes, including change in or loss of nipple sensation;  
x 
Redness or bruising;  
x 
Rupture of the breast implant;  
x 
Scarring;  
x 
Seroma; 
x 
Skin rash;  
x 
Lymphedema or lymphadenopathy; 
x 
Breast tissue atrophy; and 
x 
Unsatisfactory appearance due to implant style or size.  

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The occurrence of one or more of the above complications may require medical or surgical 
treatment, including additional surgery or implant removal.  
9.4. 
Risks Associated with Biologic Surgical Mesh 
The potential risks and benefits of participation in this trial are described in the subject informed 
consent  form  and  are  to  be  explained  to  the  subject  and/or  their  legal  representative  prior  to  
participating in the trial.   
The potential complications associated with the use of biologic surgical mesh during breast 
reconstruction are listed below.  These complications are therefore also possible with the use of 
Meso BioMatrix during breast reconstruction.  However, there may be unforeseen additional 
risks.  The potential investigational device related complications are: 
x 
Infection; 
x 
Seroma; 
x 
Hematoma; 
x 
Tissue necrosis; 
x 
Dehiscence; 
x 
Erythema; 
x 
Local or systemic allergic reaction to the Meso BioMatrix implant; and 
x 
Defect Recurrence. 
9.5. 
Risk Associated with Tissue Biopsy 
During the second stage surgery, Investigators will obtain a total of four small biopsies: One at 
the Meso BioMatrix implant superior interface, one in the center of the Meso BioMatrix implant, 
one at the Meso BioMatrix implant inferior interface and one posterior to the expander.  The risks 
associated with these tissue biopsies during the second stage surgery are: 
x 
Infection at the biopsy location 
x 
Bleeding at the biopsy location  
x 
Weakening of the tissue surrounding the biopsy location 
9.6. 
Risk Mitigation 
In order to reduce the risk of potential adverse events to subjects recruited for this trial, subjects 
with higher surgical risk factors and known confounding risk factors have been excluded.  In 
addition, subject subgroups that are known to have a reduced chance of a successful outcome (i.e. 
smokers, subjects undergoing peri-operative radiation therapy, obesity, etc.) due to confounding 
risk factors have been excluded from the trial.   
Formal trial stopping rules have been defined in section 11.4.1 to assist with limiting exposure to 
the investigational device should known serious adverse events occur at a higher than expected 
rate or potentially unforeseen risks occur in study subjects.   
It is expected that the investigational device implantation procedure will not add any significant 
additional operative time compared to the procedure as it is normally performed with AlloDerm 
or autologous tissue.  In addition, the study required antibiotic regimens are consistent with the 
study investigators’ standard of care.     
Taking biopsies from the surgical mesh during the second stage surgery may increase certain 
risks.  However, subjects will take prophylactic antibiotics to mitigate the risk of infection.  
Further, in the case of bleeding, surgeons can observe the biopsy sites during the second stage of 
the reconstruction and can address bleeding appropriately.  Lastly, the biopsy specimens will be 
quite small relative to the surface area of the surgical mesh.  Therefore, weakening of the mesh 
after biopsy is unlikely.   
The Meso BioMatrix was designed and developed according to the Quality System Regulation. 
Device sterilization has been validated.  Numerous in vivo animal studies have been conducted 

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with the Meso BioMatrix that demonstrated the biocompatibility, safety and effectiveness of the 
implant for soft tissue repair and reinforcement.  
9.7. 
Anticipated Clinical Benefits 
As described in the scientific literature, a majority of subjects who undergo tissue-expander 
assisted breast reconstruction with biologic surgical mesh experience improved aesthetic 
outcomes compared to tissue-expander assisted reconstruction without biologic surgical mesh or 
mastectomy alone.  Therefore, it is expected that the majority of subjects in this trial will also 
experience satisfactory aesthetic outcomes.  In addition, as reported in the AlloDerm literature, 
patients may experience less post-operative pain, reduced time to full expansion, reduced time 
between the first and second stage of the breast reconstruction and less capsular contracture as 
compared to two-stage, tissue-expander assisted reconstruction without a surgical mesh.  The 
information gained from the conduct of this trial may be of benefit to other people with the same 
medical condition.   
9.8. 
Alternative Treatments 
Subjects do not have to participate in this trial to receive breast reconstruction surgery.  There are 
alternative surgical methods available including direct to implant breast reconstruction, tissue 
expander-assisted implant reconstruction with an alternative biologic surgical mesh (albeit off-
label), expander-assisted implant reconstruction without a biologic surgical mesh, and autologous 
flap reconstruction.  These procedures each have different risk and benefit profiles.  Subjects are 
informed about these alternative procedures in the informed consent form and are encouraged to 
discuss them with the Investigators.   
10. TRIAL DATA COLLECTION, MONITORING AND QUALITY MANAGEMENT 
10.1. 
Data Management  
10.1.1. Clinical Trial Database 
The clinical trial database will be compliant with Part 11 of Title 21 of the United States Code of 
Federal Regulations.  Data type, range and logic verification edit checks will be programmed into 
the database.   
10.1.2. Case Report Form  
Clinical trial data were originally  recorded on  paper-based case report forms.  Those case report 
forms were printed on 3-part NCR paper and provided in single patient binders.  In the spring of 
2014, the case report forms will become electronic for the remainder of the trial.  The electronic 
case report form is eClinical OS™ (Merge Healthcare Incorporated located in Morrisville, NC).   
10.1.3. Data Entry and Quality Control 
Each field on the case report form will be entered into the clinical trial database.  Each field will 
be subjected to data type verification and range checking, as appropriate.  After a case report form 
page is entered into the database, a second staff member then compares the entered data to the 
case report form in order to identify discrepancies between the case report form and the clinical 
database.  Any identified discrepancies are resolved within the database and the reason for data 
change is recorded in the data audit trail.   
10.1.4. Data Cleaning and Editing 
Periodic analysis of each data field across all entered subjects will be performed in order to 
identify omitted data, data discrepancies and outliers for possible data mistakes.  Any discovered 
errors are then referred to the clinical site Research Coordinator or Investigator as a query on a 
data clarification form. The Research Coordinator or Investigator will review and respond to the 
query(s) on the data clarification form. Corrected data is entered in the clinical database and the 
reason for data change is recorded in the data audit trail.   

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10.1.5. Data Storage 
The clinical trial database will reside on a secure server that will be backed up on a regular basis.  
Case report forms and data clarification forms will be stored in a secure storage room.   
10.1.6. Trial Data Retention 
Clinical trial data will be maintained by DSM Biomedical for no less than two years after the 
completion or termination of the trial or no less than two years after marketing application 
approval for the investigational device, whichever event occurs the latest.  Clinical sites will be 
required to adhere to the same trial data retention period.   
10.2. 
Clinical Site Initiation 
When a site has fulfilled all relevant regulatory (i.e., FDA approval and IRB approval) and 
sponsor requirements (i.e., execution of a Clinical Research Trial Agreement, submission of 
required regulatory documents), a site initiation visit will be conducted.  At the site initiation 
visit, the clinical site’s Principal Investigator and Research Coordinator will receive training on 
the Investigational Plan and trial procedures.    
10.3. 
Trial Data Monitoring 
In order to assess the completeness and accuracy of the data provided by each site, the monitor 
will perform 100% source document verification of data in the case report form for each subject 
in the trial.  The monitor will notify the Research Coordinator and/or Investigator of any data 
discrepancies between the source medical records and the case report form found during 
monitoring.  When all fields on an individual case report form page have been verified, the 
monitor will initial and data the “Source Document Verification” box at the bottom of the page.  
The  top  two  copies  of  each  case  report  form  page  will  be  removed  and  submitted  to  data  
management.   
10.4. 
Clinical Site Closeout 
When all clinical data from each clinical site have been monitored and cleaned, a site closeout 
will be conducted.  At the closeout, the monitor will verify that clinical data for all subjects are 
present and all required regulatory documents are present and up to date.  Lastly, the monitor will 
ensure that the clinical site understands their trial data retention responsibilities.   
11. STATISTICAL CONSIDERATIONS 
11.1. 
Sample Size Justification 
This is a feasibility trial with no formal statistical hypothesis.  Therefore, the sample size of 25 
subjects was empirically chosen. 
11.2. 
Statistical Analysis 
11.2.1. Data Presentation 
All clinically relevant demographic, baseline, procedure and outcome variables will be 
summarized by scheduled visit using frequency tables and descriptive statistics as appropriate in 
accordanace with sections 8.2, 8.3, 8.4, 8.7 and 8.8 of the Guidance for Industry and FDA Staff – 
Saline, Silicone Gel and Alternative Breast Implants26.  
11.3. 
Interim Analysis Plans 
There will be no interim analysis.   
11.4. 
Criteria for Trial Termination 
All serious adverse events and unanticipated adverse device effects reported during the trial will 
be evaluated to determine if the investigational device poses an unacceptable risk to subjects.  If 
an unacceptable risk is determined in the judgment of the Investigators, the sponsor and/or the 
U.S. Food & Drug Administration, enrollment in the trial will be suspended while an 

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investigation into the cause of the unacceptable risk is undertaken.  If the unacceptable risk 
cannot be mitigated by modifications to the investigational device or the investigational plan, the 
trial will be terminated.   
11.4.1. Stopping Rules Related to the Investigational Device 
DSM Biomedical will follow the below formal stopping rules in order to assure that enrollment 
will be suspended in a timely manner should potential serious safety issues arise unique to the 
investigational device: 
x 
A serious immune reaction requiring surgical revision/removal of the investigational device 
occurs in 2 subjects. 
x 
An investigational device malfunction requiring post-operative surgical revision/removal of 
the investigational device occurs in 3 subjects. 
x 
A serious adverse event potentially related to the investigational device occurs in 5 subjects. 
x 
A serious unanticipated adverse device effect is determined to have occurred.   
Should one of the above stopping criteria occur, DSM Biomedical shall suspend enrollment as 
soon as possible, but not later than 5 working days after the determination that a stopping rule 
criterion has been met.  The trial will remain suspended until the FDA and the each IRB have 
approved trial resumption.  
11.4.2. Success Criteria 
The purpose of this study is to demonstrate the safety and feasibility of the use of the Meso 
BioMatrix device when used for two-stage, tissue-expander assisted breast reconstruction.  In 
order to warrant further study of the use of Meso BioMatrix device during breast reconstruction, 
the complications seen in this study should not be significantly greater than the complications 
seen in the AlloDerm literature.  As described in the three recent systematic literature reviews 
cited in section 4.2 of this protocol, the rates of individual breast related adverse events associated 
with the use of AlloDerm are variable and, due to the retrospective nature of many of the articles 
in the AlloDerm literature, are likely underreported.  Nonetheless, the AlloDerm literature 
provides  a  basis  for  assessing  the  initial  safety  of  the  Meso  BioMatrix  device.   Based  on  the  
AlloDerm literature (reference section 4.2), the below rates of individual Meso BioMatrix related 
adverse events will be considered clinically acceptable for this pilot phase trial and may support 
progression to a pivotal phase trial: 
x 
0% rate of death, 
x 
0% rate of anaphylaxis, 
x 
≤ 8% rate of severe acute inflammatory response, 
x 
≤ 12% rate of infection, 
x 
≤ 20% rate of flap necrosis, 
x 
≤ 10% rate of Baker Grade 4 capsular contracture in breasts that do not receive post-
operative radiation therapy.     
12. TRIAL ADMINISTRATION 
12.1. 
Trial Principal Investigator 
To be determined 
12.2. 
Sponsor 
DSM Biomedical  
735 Pennsylvania Drive 
Exton, PA 19341 USA   
Phone: 484-713-2100 
Fax: 484-713-2900  

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12.3. 
Trial Monitor(s) 
Forde Hansell  
 
 
 
Novella Clinical 
Sr. Manager, Clinical Research  
 
1700 Perimeter Drive 
DSM Biomedical  
 
 
 
Morrisville, NC 27560 (USA) 
735 Pennsylvania Drive  
 
 
Phone: 919-308-2168 
Exton, PA 19341 (USA)   
 
 
Fax: 919-484-7727 
Phone: 484-713-2152 
Fax: 484-713-2903  
 
12.4. 
Data Management 
Novella Clinical 
1700 Perimeter Drive 
Morrisville, NC 27560 (USA) 
Phone: 919-308-2168 
Fax: 919-484-7727 
12.5. 
Core Laboratory 
PPD Central Labs 
2 Tesseneer Drive 
Highland Heights 
KY 41076- 9167 (USA) 
Phone: 910-558-4807 
Fax: 859-781-9310 
13. ADVERSE EVENT REPORTING 
13.1. 
Adverse Events 
At each evaluation, the investigator will determine whether any adverse events (AEs) have 
occurred, whether expected or not.  Adverse events occurring between required study visits will 
be recorded on the case report form of the next required visit.  For the purpose of this protocol, an 
adverse event is any untoward medical occurrence in a subject.  All AEs occurring during the trial 
period will be recorded in the case report form.   
13.1.1. Adverse Event Severity 
For the trial, the Investigators will categorize and report the severity of adverse events as follows: 
x 
Mild = The AE is transient and easily tolerated by the subject. 
x 
Moderate = The AE causes the subject discomfort and interrupts the subject’s normal 
activities. 
x 
Severe = The AE: 
o is life threatening; 
o results in permanent impairment of a body function or permanent damage to a body 
structure;  
o necessitates medical or surgical intervention to preclude permanent impairment of a body 
function or permanent damage to a body structure; or 
o results in hospitalization or prolongation of hospitalization.   
13.1.2. Adverse Event Relatedness 
The Investigators will also categorize and report the relatedness of the AEs as follows: 
x 
Systemic = adverse events that are not related to the target breast (e.g. pulmonary embolus, 
allergic reactions to general anesthesia, illness, etc.) 
x 
Related to Target Breast = adverse events that occur in or around the target breast that cannot 
be directly attributed to the implanted Meso BioMatrix (e.g. hematoma, pain, etc.). 

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x 
Related to Investigational Device = adverse events that may be directly linked to the 
implanted Meso BioMatrix. 
x 
Related to Prosthesis = adverse events that may be directly linked to the tissue expander or 
breast implant.    
13.1.3. Immediate Post-operative Symptoms as Adverse Events 
Subjects in this trial will undergo two, possibly three, breast related surgeries.  Pain, redness and 
swelling at the surgical site will occur in every subject following each surgery.  Therefore, 
immediate post-operative symptoms and function restrictions will only be categorized as adverse 
events when a subject's complaint for any of these symptoms results in an unscheduled visit or 
when a subject presents with new or worsening symptoms as compared to the previous visit. 
13.2. 
Serious Adverse Events 
Serious adverse events (“SAEs”) in this trial are adverse events that meet the definition of severe 
in section 13.1.  All SAEs will be documented on the case report form.  Investigators must also 
report SAEs to DSM Biomedical and the relevant Institutional Review Board within 48 hours of 
learning of the SAE.  The Investigator shall make such notification to the sponsor on a Report of 
Serious Adverse Event in the case report form. 
13.3. 
Unanticipated Adverse Device Effects  
An unanticipated adverse device effect (“UADE”) is defined as either: 
x 
any serious adverse effect on 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  
x 
any other unanticipated serious problems associated with a device that relates to the rights, 
safety, or welfare of subjects. 
Investigators must report UADEs to DSM Biomedical and the relevant Institutional Review 
Board within 48 hours of learning of the UADE.  The Investigator shall make such notification on 
a  Report  of  Serious  Adverse  Event  form  and  document  the  UADE  on  the  case  report  form.    
Following the report of the UADE, DSM will immediately conduct an investigation to determine 
the  cause  of  the  UADE  and  assess  the  level  of  risk  to  current  and  potential  future  research  
subjects.  DSM will report the results of UADE evaluations, including any identified corrective 
actions, to FDA, all reviewing IRBs and all participating investigators within 10 working days 
after DSM first receives notice of the UADE.  If DSM determines that the UADE presents an 
unreasonable risk to subjects based on a risk analysis, DSM shall terminate enrollment as soon as 
possible, but not later than 5 working days after this determination and not later than 15 working 
days after DSM first received notice of the UADE.   
14. TRIAL RESPONSIBILITIES 
14.1. 
General Responsibilities 
14.1.1. Subject Confidentiality 
Subject confidentiality is of utmost importance to all parties involved in this trial.  DSM 
Biomedical, the Investigators, all assisting contract research organizations, monitors and the Core 
Lab will take appropriated steps to protect the identity of research subjects as stated in the HIPAA 
law.    
14.1.2. Good Clinical Practice Guidelines 
DSM Biomedical, the Investigators, all assisting contract research organizations, monitors and the 
Imaging Core Lab will follow Good Clinical Practice Guidelines (GCP) in the conduct of this 
trial. 
14.2. 
Investigator Responsibilities  

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The investigator is responsible for ensuring the investigation is conducted according to all signed 
agreements and the Investigational Plan.  This section further describes each Investigator’s 
responsibilities.   
14.2.1. Institutional Review Board (IRB) Approval 
The investigator must submit the trial protocol to his/her IRB and obtain their written approval 
before being allowed to enroll subjects in the trial.  The investigator is also responsible for 
fulfilling any conditions of approval imposed by the IRB, such as regular reporting, reporting of 
SAEs, etc. 
14.2.2. Informed Consent Form 
Part of the IRB approval must include approval of the Informed Consent Form specific to this 
trial.  The investigator must administer the approved Informed Consent Form to each prospective 
trial subject, and obtain the subject's signature on the on the Informed Consent Form, prior to 
enrollment  in  the  trial.   The  sample  Informed  Consent  is  included  in  section  7  of  the  
Investigational  Plan.   The  sample  Informed  Consent  Form  may  be  modified  to  suit  the  
requirements of the individual site and IRB. 
14.2.3. Protocol Compliance 
Investigators must not deviate from the protocol.  The only allowable exceptions are in cases of 
emergency to protect subject safety.  All deviations from the protocol must be recorded in the 
case report form along with an explanation for the deviation.  Continued deviations from the 
protocol may lead to termination of the investigator’s participation in the trial. 
14.2.4. Records 
Each investigator must maintain current, precise and safeguarded records relating to the conduct 
of the investigation kept in a locked and restricted access area.  These records include:  
x 
correspondence with the IRB and the Sponsor,  
x 
records of receipt, use and disposition of trial devices, 
x 
records of each subject’s trial participation.   
Each investigator must retain the records of the investigation for at least 2 years after the 
completion of the trial or 2 years after the approval of a marketing application in the United 
States, whichever occurs last. 
14.2.5. Reports 
Investigators are responsible for reports of serious adverse events, unanticipated device effects, 
withdrawal of IRB approval, deviations from the investigational plan, use of the device without 
consent,  progress  reports  and  final  reports.   These  reports  must  be  submitted  to  the  IRB  and  
copies must be submitted to the Sponsor.  Investigators must report serious adverse events and 
unanticipated adverse device effects to the sponsor with 48 hours of learning of the event.   
14.3. 
Sponsor Responsibilities  
DSM Biomedical is the sponsor of the trial. DSM Biomedical’s responsibilities in the trial 
include: 
14.3.1. Quality Assurance and Quality Control 
Implement and maintain quality assurance and quality control to ensure the trial is conducted 
according to the Investigational Plan and applicable laws and regulations.   
14.3.2. Investigational Plan Approval 
Provide the Investigational Plan to the applicable regulatory authorities and to the Investigators.  
DSM Biomedical will ensure the Investigational Plan is approved by the applicable Institutional 
Review Board at each site prior to first subject enrollment.   

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14.3.3. Ensure Compliance with Investigational Plan and Regulations 
DSM Biomedical will ensure the Investigators and all contracted parties comply with the 
Investigational Plan and all applicable regulations.  If non-compliance is identified, DSM 
Biomedical shall take prompt and appropriate action to secure compliance or terminate the 
Investigator’s or contracted party’s participation in the trial.      
14.3.4. Device Supply and Accountability 
Provide properly labeled and packaged investigational devices to the participating trial sites in a 
quantity sufficient to support trial activities.  DSM Biomedical will maintain a master record of 
all supplied, used, returned and destroyed investigational devices. 
14.3.5. Device Training 
Provide investigational device training to Investigators and trial site staff. 
14.3.6. Investigator Selection 
Select the Principal Investigator, all clinical investigators at the trial sites, and any consultants 
who participate in the trial.  Eligible Investigators are those who are experienced in the treatment 
of the target population and who agree to allow direct access to trial records for the purpose of 
monitoring and auditing trial data.   
14.3.7. Financial Support 
Provide financial support at fair market value to the Investigators and/or personnel at the trial site 
in order to adequately conduct the trial. 
14.3.8. Establish Regulatory Standards 
Establish the regulatory standards to be followed for the clinical trial and other participants.  All 
trial participants shall follow GCPs.   
14.3.9. Monitoring Oversight 
Assure site monitoring is performed in compliance with applicable regulations. 
14.3.10. Safety Oversight 
Monitor the safety of the use of the investigational device on an ongoing basis.  If a significantly 
greater rate of SAEs or other adverse events are observed, it is the sponsor’s responsibility to 
suspend enrollment in the trial to prevent subjects from being exposed to unnecessary risks while 
the root cause is being determined.  DSM Biomedical shall promptly inform the Principal 
Investigator and the Site Principal Investigators about any UADEs occurring during the trial.  
Such notification shall be sent in writing. 
14.3.11. Trial Reports 
Provide annual progress reports and the final trial report to the Investigators and applicable 
regulatory authorities.   
14.3.12. Trial Registration 
Register the trial on the clinicaltrials.gov website if required in Title VIII of the Food and Drug 
Administration Amendments Act of 2007.   
14.4. 
Monitor Responsibilities 
The monitors are responsible for the following: 
14.4.1. Ensuring Compliance with the Investigational Plan and Applicable Regulations 
Ensure the rights, safety and welfare of trial subjects are being protected as required by the 
Investigational Plan and applicable regulations.  Ensure the Investigators are complying with the 
procedures in the Investigational Plan.  Ensure the Investigators are properly protecting and 
accounting for investigational devices.  The monitor will also determine if the Investigator is 
maintaining the necessary regulatory documents.   

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14.4.2. Verifying Trial Data 
Verify data on the case report form against the source documents for completeness and accuracy. 
Inform the Investigator and/or Research Coordinator of any discrepancies between the data on the 
case report form and the source documents and ensure appropriate corrections are made.  Ensure 
all protocol deviations and adverse events are properly reported on the case report form.  
15. PUBLICATION POLICY 
DSM Biomedical retains ownership of all clinical data generated in this trial, and controls the use 
of the data for purposes of regulatory submissions.  DSM Biomedical will exercise no veto over 
publication of trial results in the medical literature but must be provided with advance copies of 
manuscripts and abstracts to review for technical accuracy and confidential information.  
However, the Principal Investigator for the trial shall have first right of publication.  No 
individual site experiences may be published prior to the principal trial manuscript without the 
expressed consent of the Principal Investigator and DSM Biomedical. 
16. REFERENCES 
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partial detachment of the pectoralis major muscle to expand the lower breast quadrants.  Ann Plast 
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2. Namnoum JD.  Expander/Implant reconstruction with AlloDerm: recent experience.  Plast Reconstr 
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3. Breuing KH and Warren SM.  Immediate Bilateral Reconstruction with Implants and Inferolateral 
AlloDerm Slings.  Ann Plast Surg 2005; 55(3): 232-239. 
4. Salzberg CA.  Nonexpansive immediate breast reconstruction using human acellular tissue matrix 
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6. Zienowicz RJ, Karacaoglu E.  Implant-based breast reconstruction with allograft.  Plast Reconstr 
Surg  (2007); 120(2):373-381. 
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in Postmastectomy Breast Reconstruction J Plas Reconstr Aesth Surg 2007; 60:1214-18. 
8. Spear SL, Newman MK, Bedford MS et al.  A Retrospective Analysis of Outcomes Using Three 
Common Methods for Immediate Breast Reconstruction  Plast Reconstr Surg 2008; 122:340-347. 
9. Chun YS, Verma K, Rosen H et al.  Implant-Based Breast Reconstruction Using Acellular Dermal 
Matrix and the Risk of Postoperative Complications  Plast Reconstr Surg 2010; 125:429-436. 
10. Lanier ST, Want ED, Chen JJ et al.  The Effect of Acellular Dermal Matrix Use on Complication 
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11. Nguyen MD, Chen C, Colakoğlu S et al.  Infectious Complications Leading to Explantation in 
Implant-Based Breast Reconstruction with AlloDerm  ePlasty 2010; 10: 404-410. 
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15. Sbitany H, Sandeen SN, Amalfi AN et al.  Acellular Dermis-Assisted Prosthetic Breast 
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Guidance 
Document: 
Tissue 
Expander, 
available 
at: 
http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm07081
9.htm#5 
23. Mentor 
Tissue 
Expander 
Instructions 
For 
Use. 
 
Available 
at: 
http://www.mentorwwllc.com/Documents/smooth_tissue_expander.pdf.  Accessed on December 15, 
2011. 
24. Allergan
 Style
 133V
 Series
 Tissue
 Expander
 Instructions
 for
 Use.
  Available
 at:
  
http://www.allergan.com/assets/pdf/M724-B_133V_TE_DFU.pdf.  Accessed on December 15, 2011. 
25. U.S. Food & Drug Administration’s Breast Implant Complication Booklet available at: 
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mplants/ucm259296.htm. 
26. Guidance  for  Industry  and  FDA  Staff  –  Saline,  Silicone  Gel  and  Alternative  Breast  Implants.   
Available 
on 
the 
U.S. 
Food 
& 
Drug 
Administration 
website 
at: 
http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm07122
8.htm.