Application of RECELL to Promote Healing Following CO2 Laser Treatment in Cosmetic Facelift Patients
Phase: PHASE4
Conditions: Carbon Dioxide Laser, Photoaging
Sponsor: Wake Forest University Health Sciences

 
 
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Application of RECELL to Promote Healing Following CO2 Laser 
Treatment in Cosmetic Facelift Patients 
 
IRB00085278 
 
NCT05386368 
 
IRB Approval Date:  05/04/2023 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
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Study Title: Application of RECELL to Promote Healing Following CO2 Laser Treatment in 
Cosmetic Facelift Patients  
 
Principal Investigator:  Joseph Molnar, MD, PhD  
 
Co-investigator(s): Ramon Llull, MD, PhD, Anthony DeFranzo, MD, Christopher Runyan, MD, 
Robert Siska, MD, Abby Peoples, BA, Caitrin Curtis, MD, Amelia Davidson, BS  
 
Sponsor or funding source: Department of Plastic and Reconstructive Surgery, RECELL 
product provided by Avita Medical 
 
Background, Rationale and Context 
 
The RECELL system is a regenerative epidermal harvesting device that is currently FDA 
approved for use in treatment of partial thickness burns in adults. The system works by 
enzymatically processing a small sample of the patient’s skin to create a regenerative epidermal 
suspension (RES) graft that can be sprayed onto a burn wound. Contained within the RES is a 
mix of keratinocytes, fibroblasts, and melanocytes.1,2 The advantage of using the RECELL 
system over traditional skin grafting techniques is that, when enzymatically processed, donor 
tissue can be applied to re-epithelialize a significantly larger area than traditional skin grafting 
techniques. RES usually allows an 80:1 donor site to graft site expansion ratio.3,4   
 
While RES has been most extensively used in burn treatment, it has also been used with success 
following CO2 laser resurfacing for the treatment of vitiligo and for enhanced healing following 
microdermabrasion.5,6 A decade of precedent exists for treating patients with vitiligo through a 
combination of CO2 laser and regenerative epidermal suspension grafting with the goal of 
improved skin pigment after re-epithelialization.7 A 2019 study assessed the healing time with 
and without RECELL application in 78 patients undergoing microdermabrasion for acne scare 
treatment. They study found a statistically significant decrease in healing time between the two 
groups, with the RECELL group (n = 48) healing in an average of 5.27 days and the group with 
microdermabrasion alone (n= 30) healing in an average of 12.3 days; healing time was defined as 
total epithelialization duration.8   
 
With the safety and efficacy of RES demonstrated in multiple clinical contexts, our study aims to 
ascertain if RES can be used for cosmetic purposes to enhance healing following CO2 partial 
field ablation. CO2 laser resurfacing is often used as an adjunct treatment during facelift 
procedures to address signs of aging in the periorbital and perioral areas. The laser treatment 
works by a superficial layer of the skin, requiring complete reepithelialization of laser treated 
areas. This process results in significant post-operative erythema, pain, and downtime for the 
patient. During the facelift procedure, excess skin is removed and discarded. In our proposed 
study, this excess skin would be repurposed via processing with the RECELL system to be used 
as a regenerative epidermal suspension graft on CO2 laser treated areas. The excess skin 
removed on a facelift is a greater surface area than the required 2 x 3 skin graft that is required 
for the common 80:1 expansion used in burn surgery. Therefore, we should have significant 
amounts of excess skin that could be repurposed as a split thickness skin graft that can be used 
for the recell. There will not be any additional skin removed further than what is required for the 

 
 
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facelift. We will use an 0.008 inch Weck blade to repurpose the excess skin into a split thickness 
skin graft need for the recell.  
 
 
Device Output Characterization 
We do not have any plans for this.  
 
Objectives 
The primary objective and study endpoint will be safety. The number of skin reactions will be 
evaluated to measure the primary endpoint over the treated area vs placebo control.  
 
Methods and Measures 
 
Design 
Randomized, Double Blind, Placebo Controlled  
 
Setting 
Atrium Health Wake Forest Baptist Department of Plastic and Reconstructive 
Surgery 
 
Subjects selection criteria 
 
• Inclusion Criteria 
Adults 22 years or older  
Patients undergoing facelift with perioral CO2 laser treatment  
Skin that is Fitzpatrick Score 1 or 2 
 Subjects who are in general good health 
Subjects who fully understand the research nature of this study and sign the 
informed consent 
  
• Exclusion Criteria 
Prior perioral CO2 laser resurfacing  
Allergy to components of preparation system 
Subjects who have cosmetic or surgical treatment in perioral area within 3 months 
before the study (including laser, chemical peels, fillers, botulinum toxin). 
Subjects with existing open wounds on the face 
Subjects with active cutaneous infection, acne, dermatitis or any active dermal 
disease on the face 
Subject with signs of hypersensitivity or inflammation on the face 
Subjects with known hypersensitivity to trypsin or compound sodium lactate 
solution (Hartmann’s Solution) 
Subjects with known hypersensitivity to anesthetics, adrenaline/epinephrine, 
povidone-iodine, or chlorhexidine solutions. 
Subjects with any disease/condition that may affect wound healing such as 
diabetes or obesity 
Subjects with any bleeding disorder  

 
 
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Subjects with any existing malignancy  
Subjects who are pregnant, breastfeeding, or whose urinary pregnancy test is 
positive before participation in the study 
Subjects with any disease/condition deemed unsuitable for facelift surgery or 
RECELL treatment by the treating physician 
 
• Sample Size 
10 patients 
 
Interventions and Interactions 
 
The perioral area of the face will be treated with CO2 laser. Laser setting will be determined by 
the treating surgeon for each individual patient. The laser is a Lumenis Ultrapulse/Surgitouch 
CO2 laser, 510(k) Number K030147. A laser (light amplification by stimulated emission of 
radiation) based device having coherence, collimated and typically monochromatic radiation. 
Typically indicated to cut, destroy, remove or coagulate tissue, generally soft tissue, for general 
surgical purpose in medical specialties of general and plastic surgery, dermatology/aesthetic, 
podiatry, otolaryngology (ent), gynecology, neurosurgery, orthopedics (soft tissue), dental and 
oral surgery, and dentistry. The classification regulation 21 cfr 878.4810 describes a device that 
is carbon dioxide or argon laser intended to cut, destroy, remove or coagulate tissue by the light.   
This laser is typically used in our practice for skin resurfacing to reduce the signs of aging, 
improve skin texture, laxity and tone, and reduce scars and stretch marks. Typical settings to be 
used for severe facial photoaging with Total FX is: Active FX,  Energy (mj) 100-125, Scan Size 
6-7 mm, Density 2-3, Hertz 100-200, Repeat Delay 0.3-1.5 seconds, number of passes 2. Deep 
FX,  Energy (mj) 12.5-22.5, Scan Size 10 mm, Density 5-20%, Hertz 300-600, Repeat Delay 
0.3-1.5 seconds, Number of Pulses 1-2, number of passes 1-2.    The patient would be 
randomized and blinded to either left perioral or right perioral RECELL application. The surgeon 
would also be blinded to which side received RECELL treatment or Placebo (saline spray). 
Randomization would occur before study initiation with subjects assigned either left perioral or 
right perioral RECELL treatment based on their subject enrollment number. The study team 
member who prepares and blinds the RECELL will create the list of subject ID numbers with 
subject ID number randomly assigned to either left perioral or right perioral treatment group. 
This will be completed prior to any patient enrollment in the study. This spreadsheet will be 
password protected and only accessible to study coordinators and the team member responsible 
for preparing RECELL. 
  
RECELL® is a single-use, stand-alone, battery-operated, regenerative epidermal harvesting 
device containing enzymatic and delivery solutions, sterile surgical instruments, and actuators. 
The cell suspension contains a mixed population of cells, including keratinocytes, fibroblasts, 
and melanocytes, obtained from the disaggregation of the skin sample.  The Enzyme used to 
process the cells is a biological agent and as such may have slight variations in color and texture. 
The enzyme is derived from animal tissue and has undergone filtration and terminal sterilization 
by gamma irradiation.  
 
Intraoperatively, RECELL and Placebo will be provided to surgeons and assistants in opaque 
application devices prepared by a trained, designated study team member.  

 
 
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Both the treatment and placebo sides, will be dressed with a standard regenerative epidermal 
suspension post treatment dressing (Telfa Clear and Xeroform). Xeroform will be removed on 
postoperative day 1. Telfa clear will be removed on postoperative day 7. Patients will return to 
clinic for follow up at the following interval:  
• Post Operation Day 1 
• Post Operation Day 7 
• Post Operation Day 14 
• 1-month Post Operation 
• 2-months Post Operation 
• 3-months Post Operation 
 
There is always a chance the patient may need to be withdrawn from the study. The main 
consideration for stopping is the dressings, as the Recell will already be sprayed. If the patient 
cannot tolerate the dressings, we will stop and remove them from the study.  Otherwise, we will 
deal with complications similar to how we would deal with other laser reactions- local wound 
care, anti-virals, etc.  
 
Any signs of anaphylactic events will lead to the study stopped immediately and unbinding. We 
will immediately wash the cell suspension off of the face with 3 liters of normal saline (NS) 
while treating the anaphylaxis per institutional protocol (including submuscular epinephrine).  
 
Any high incidence of serious adverse events (any serious adverse event, including severe 
infection requiring return to the operating room) will warrant early unbinding and assessment of 
safety immediately.  
 
Subjects will be able to withdraw from the study for any reason and at any time. We can remove 
the cell suspension with removal of dressings and 3 liters of NS wash.   
 
  
Outcome Measure(s) 
 
Preoperatively patient baselines will be established with standardized studio photographs, and 
photos using the Quantificare LifeViz® Camera, as well as in person evaluation.  
 
Intraoperatively, the patient will be photographed in CO2 treated areas with the Quantificare 
LifeViz® Camera and standardized photography. This camera measures lines, closing surfaces, 
volume, depth, and perimeter of the skin surface for microstructure analysis. We will analyze 
this data to track progress throughout the study. 
 
Postoperatively, patients will be evaluated at each visit via in person evaluation by the surgeon, 
as well as using standardized photography, Quantificare LifeViz® Camera photos, 
administration of applicable FACE-Q scales (patient completed survey), and pain score (standard 
1-10 pain scale).  Please find FACE-Q scales in Appendices B-H.  
 
Please find study calendar in Appendix A.  
 

 
 
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Analytical Plan 
Results will be analyzed initially using descriptive statistics.  Comparison between groups will 
be done using Fisher’s exact tests for proportions, and t-tests or ANOVA procedures for 
continuous variables.  Regression analysis will be performed to identify independent outcome 
predictors.  Other inferential statistical analysis will be conducted as appropriate. 
 
Human Subjects Protection 
Collection of patient-identifying information will be limited to what is necessary to conduct 
analysis that is accurately linked to a given subject. Other than the master ‘linkage’ file, patient 
names, and medical record numbers will be removed and subjects will be associated with an 
abstracted unique Study ID. DOB will only be collected in order to dynamically calculate age at 
operative and follow up time points. Data will be stored electronically on the Wake Forest 
School of Medicine’s secure REDCap server, a HIPAA-compliant web platform.  Information 
for each subject will be entered directly from EPIC to the secure REDCap database, so data will 
not be stored on portable storage devices (including USB drives). In addition to study informed 
consent, photography consent will be obtained.  
 
 
 
Subject Recruitment Methods 
Patients who are scheduled to undergo elective facelift surgery with perioral CO2 laser 
resurfacing will be identified in the Plastic Surgery Clinics at both Janeway Tower and Vest Mill 
office locations. Any patient meeting inclusion criteria will be recruited during preoperative 
planning. Patients will have study information provided by a qualified study team member. 
There will be no compensation provided for this study, but the laser will be offered at no cost for 
participants.   
 
Informed Consent 
Informed consent will be obtained by approved study personnel after study purpose, duration, 
interventions, benefits and risks are thoroughly discussed with the subject. After the entire 
consent has been reviewed and all questions have been answered, potential subjects will be given 
the option to participate. A copy of the signed and dated consent form will be given to each 
enrolled subject and one placed on the chart. The original will be kept with research study 
records. In addition, a consent for photography and photograph use in research and publication 
will be obtained and placed in the chart prior to study participation. Please see a copy of 
Informed Consent in Appendix I.  
 
Confidentiality and Privacy 
Confidentiality will be protected by collecting only information needed to conduct outcomes 
research and related research to improve facelift and CO2 laser resurfacing outcomes. All 
database data will be entered into the Wake Forest School of Medicine’s secure REDCap server. 
To help ensure subject privacy and confidentiality, a linkage file will be maintained containing 
each patient’s medical record number and unique REDCap ID. Patient names will not be 
maintained in this file. The linkage file will be stored separately from the data available to 
researchers and will be kept secure, with access limited to designated study personnel. Data 
access will be limited to study staff.  Data and records will be kept locked and secured, with any 

 
 
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computer data password protected.  No reference to any individual participant will appear in 
reports, presentations, or publications that may arise from the study however patient photographs 
may appear in publications with patient consent.  
 
Data and Safety Monitoring 
The principal investigator will be responsible for the overall monitoring of the data and safety of 
study participants.  The principal investigator will be assisted by other members of the study 
staff. 
Additional safety assessment will include a full medical history and physical before proceeding 
with study activities.  
 
Reporting of Unanticipated Problems, Adverse Events or Deviations 
Adverse events would include the inability to tolerate dressings, deeper burns - including 
blistering burns or full-thickness burns - which would be managed with local wound care as we 
would manage any other burn in our burn center. We will record any viral outbreaks and any 
need for antivirals (such as HSV outbreaks from burn or recell). Given the fact that we are doing 
a controlled burn, the adverse outcome for "burns," will be blistering burn, signifying a deeper 
than expected burn from the laser. 
We will assess for adverse events at each follow-up visit.  Follow-up visits will include 
photography and assessment for adverse events.  
Any unanticipated problems, serious and unexpected adverse events, deviations or protocol 
changes will be promptly reported by the principal investigator or designated member of the 
research team to the IRB and sponsor or appropriate government agency if appropriate. 
We will report all adverse events to the FDA as described in 21 CFR 312.32. 
 
 
Risk Analysis 
Given that Recell is a product that speeds up wound healing, we do not anticipate that it will 
lengthen the wound healing course for the laser.  
 
 
 
References  
1.  
Hirobe T. Keratinocytes regulate the function of melanocytes. Dermatologica Sin. 
2014;32(4):200-204. doi:10.1016/J.DSI.2014.05.002 
2.  
Wood F, Giles N, Stevenson A, Rea S, Fear M. Characterisation of the cell suspension 
harvested from the dermal epidermal junction using a ReCell® kit. Burns. 2012;38(1):44-
51. doi:10.1016/J.BURNS.2011.03.001 
3.  
Holmes IV J, Molnar J, Carter J, et al. A Comparative Study of the ReCell® Device and 
Autologous Spit-Thickness Meshed Skin Graft in the Treatment of Acute Burn Injuries. J 
Burn Care Res. 2018;39(5):694-702. doi:10.1093/JBCR/IRY029 
4.  
Holmes J, Molnar J, Shupp J, et al. Demonstration of the safety and effectiveness of the 
RECELL ® System combined with split-thickness meshed autografts for the reduction of 
donor skin to treat mixed-depth burn injuries. Burns. 2019;45(4):772-782. 
doi:10.1016/J.BURNS.2018.11.002 
5.  
Lommerts JE, Meesters AA, Komen L, et al. Autologous cell suspension grafting in 

 
 
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segmental vitiligo and piebaldism: a randomized controlled trial comparing full surface 
and fractional CO2 laser recipient-site preparations. Br J Dermatol. 2017;177(5):1293-
1298. doi:10.1111/bjd.15569 
6.  
Ren J, Liu J, Yu N, et al. The use of noncultured regenerative epithelial suspension for 
improving skin color and scars: A report of 8 cases and review of the literature. J Cosmet 
Dermatol. 2019;18(5):1487-1494. doi:10.1111/jocd.13071 
7.  
Van Geel N, Wallaeys E, Goh BK, De Mil M, Lambert J. Long-term results of 
noncultured epidermal cellular grafting in vitiligo, halo naevi, piebaldism and naevus 
depigmentosus. Br J Dermatol. 2010;163(6):1186-1193. doi:10.1111/j.1365-
2133.2010.10014.x 
8.  
Chen Q, Yu N, Liu Z, et al. The Clinical Efficacy of ReCell® Autologous Cell 
Regeneration Techniques Combined with Dermabrasion Treatment in Acne Scars. 
Aesthetic Plast Surg. 2020;44(2):535-542. doi:10.1007/s00266-019-01481-8 
 
Appendix 
A. Study Calendar  
B. Preoperative Scale 
C. FACE-Q POD 1 Scales 
D. FACE-Q POD 7 Scales  
E. FACE-Q POD 14 Scales 
F. FACE-Q 1 Month Scales  
G. FACE-Q 2 Month Scales  
H. FACE-Q 3 Month Scales  
I. Informed Consent – Created following final protocol approval 
J. Photography Consent – standard departmental photography consent