Utility of Restrata With Split Thickness Skin Graft to Reconstruct the Forearm Donor Site
Phase: NA
Conditions: Wound Heal
Sponsor: Acera Surgical, Inc.

Title: Utility of Restrata With Split Thickness Skin Graft to Reconstruct the Forearm Donor Site 
NCT Number: NCT04829331 
ID: 21-RES-003 
Document Date: 22 APRIL 2021 
 

Title:
Utility of Restrata with split-thickness skin graft to reconstruct the forearm donor site.
Objective:
Understand association between use of Restrata (Acera Surgical Inc., St. Louis, MO) in forearm 
flap reconstruction with donor site healing and function.
Hypothesis:
Use of Restrata in combination with split-thickness skin graft for reconstruction of forearm flap 
reconstruction donor site will be associated with decreased occurrence of tendon exposure at four
weeks post-operatively when compared to split-thickness skin graft alone.
Design:
Randomized controlled trial.
Setting:
Single institution, Nebraska Methodist Medical Center
Population:
Adult patients undergoing radial forearm free flap or ulnar forearm free flap at a single 
institution.
Intervention:
Reconstruction of forearm harvest site using Restrata with a split-thickness skin graft.
Control:
Reconstruction of forearm harvest site using split-thickness skin graft alone.
Inclusion Criteria:
1. All patients age 19 or greater that will undergo radial forearm free flap or ulnar free flap.
2. Photo documentation of wound bed at two weeks and four weeks must be obtainable either 
by physician or patient.
Exclusion Criteria:
1. Active systemic immunosuppression (active use of high-dose steroids (≥40mg prednisone 
daily or equivalent) or other immunosuppressive medications OR medical conditions causing
immunosuppression, i.e. human immunodeficiency virus etc).
2. Diabetes mellitus with most recent Hemoglobin A1c ≥10.0 within 30 days prior to surgery.
3. Morbid obesity (BMI >40).
4. Inability to maintain wrist immobilization for full planned period.
5. Severe malnutrition (prealbumin levels <10 mg per dL within 30 days prior to surgery OR 
BMI <15 (very severely underweight).
6. Other conditions felt to significantly impair wound healing per surgeon discretion.
Primary Outcomes:
1. Tendon exposure at four weeks post-operatively (Yes/No).

2. Percentage of surface area of split-thickness skin graft incorporation at four weeks post-
operatively.
Secondary Outcomes:
1. Tendon exposure at two weeks post-operatively (Yes/No).
2. Percentage of surface area of split-thickness skin graft incorporation at two weeks post-
operatively.
3. Aesthetic appearance of donor site per surgeon rating (graded 1-10).
4. In patients with tendon exposure, time to complete wound epithelialization (measured as time
from surgery to first documentation of complete epithelialization in days).
5. Need for re-operation on forearm or secondary wound care strategy after tendon exposure.
6. Forearm infection requiring surgical drainage and/or antibiotics.
Goal Enrollment:
40 total patients with 1:1 group enrollment.  Power analysis was performed to identify necessary 
sample size to detect an absolute reduction of tendon exposure at four weeks of 15% (25% 
baseline, 10% expected rate with intervention with power of 80% and alpha 0.05).  Under these 
assumptions, 100 patients would need to be recruited into each arm.  Recent historical review of 
institutional volume demonstrates a rate of approximately 35 forearm flaps annually (2019-2020 
data).  Assuming a 70% study enrollment rate, we would meet enrollment goals in approximately
eight years.  This time commitment is felt by the study authors to exceed what is reasonable 
without first generating preliminary data.  The proposed sample size is therefore practically 
derived based annual surgical volume at this institution and available resources from our industry
partner.  We recognize the limitations in this study, therefore, and that this design is not truly 
hypothesis testing.  Using the above assumptions, we expect goal enrollment to be met within 
approximately 18 months. 
Covariates Recorded:
1. Demographic data - Age, sex, race, ethnicity, BMI.
3. Medical history - Modified frailty index - 5, diabetes mellitus, coronary artery disease, 
peripheral artery disease, immunosuppression.
4. Social history - Smoking status (current/former/never, total py), alcohol use pattern 
5. Wound surface area in square cm.
Randomization:
Occurs when the patient is scheduled for surgery.  A simple randomization strategy will be 
utilized by creating a randomization list using 
https://www.graphpad.com/quickcalcs/randomize1/, which will ensure equal group distribution.  
The surgery scheduler will assign patients to their category based on this pre-determined list in 
consecutive order based on date of surgery scheduling request rather than surgical date to 
minimize risk of bias.
Consent:
Written informed consent will be obtained at the time of study enrollment and will be stored 
securely by the Methodist research office.  This form is separately attached.

Protocol:
1. All forearm and ulnar flaps will be harvested using a suprafascial harvest technique.
6. Surgical technique for application of Restrata with split-thickness skin graft.
1. Restrata will be meshed in a 1:2 fashion to allow for egress of serous fluid and minimize 
risk of fluid collection.
2. Restrata will be applied to the entire wound bed not amenable to primary closure and will
be underlaid beneath the surrounding skin edges.
3. A split-thickness skin graft is harvested from patient’s thigh at 15:1000 inches and placed 
on top of the Restrata to cover the entire wound bed.  The graft is sutured in place using 
suture choice of surgeon’s preference.
4. Ultrasound gel is applied to the graft and matrix.
5. Xeroform gauze bolster is placed over the wound and secured using suture choice of 
surgeon’s preference.
6. The wrist is wrapped with kerlix gauze and the wrist is immobilized 
7. Bolsters are removed at five days, the wound is inspected, and high-definition digital 
photographs are obtained.
8. The arm remains immobilized for two weeks, and daily xeroform dressing changes are 
performed by patients, family, or home health per treatment team discretion.
9. Immobilizers are removed at initial follow-up visit at two weeks and high-definition digital 
photographs are obtained. (Any visit between 12 and 16 days will be considered acceptable 
as two-week follow-up).
10. If graft incorporation is adequate at two-week follow-up per treating physician discretion, 
Vaseline® or alternative non-antibiotic ointment will be applied to the graft edges between 
two and four-week follow-up visits by patients, family, or home health per treatment team 
discretion.  If graft failure occurs by two-week follow-up, Aquacel Ag (ConvaTec Medical 
Group.  Deeside, UK) will be applied to the areas of graft failure as the primary treatment 
strategy with daily dressing changes.
11. High-definition digital photographs are obtained at four-week follow-up.
12. If graft incorporation is adequate at four-week follow-up per treating physician discretion, no
additional wound care will be performed.  If graft failure occurs by four-week follow-up, 
Aquacel Ag will be applied to the areas of graft failure as the primary treatment strategy with
daily dressing changes.
13. If at any point the treating physician feels that the primary treatment strategy is inadequate or
inappropriate, a secondary wound care strategy (alternative treatment, negative pressure 
therapy, surgical debridement, repeat grafting, etc) may be pursued.
14. In any case of incomplete graft incorporation and/or tendon exposure, further photo 
documentation will be obtained by the patient, family, or home health or wound team, or 
physician until epithelialization is complete and further wound care is no longer needed.  
Details of continued follow-up visits and methods of further documentation will be 
individualized so as to minimize excessive demands on patient resources.
15. Photos of donor sites at each time period will be submitted for evaluation by two independent
surgeons who possess expertise in evaluation of free flap donor site wounds and skin grafts 
but who will not be involved in enrollment of patients in this trial or of management of their 
wounds.  The percentage of graft incorporation and presence or absence of tendon exposure 
will be documented by each physician in a blinded fashion.  The independent surgeons will 
also rate donor site graft aesthetic appearance on a 1-10 scale in a blinded fashion.  Time to 

complete epithelialization will be determined by the treating physician, and photo 
documentation will be submitted for blinded review by the independent surgeons.  Any case 
of failed epithelialization that does not completely epithelialize within 90 days after surgery 
will be categorized as “greater than 90 days for analysis”, and all study-related patient 
contact will cease at that time.
16. Descriptive statistics will be reported.  Univariate statistics will be used to compare primary 
and secondary outcomes between groups.
Premature Termination of Study:
This study may be prematurely terminated by the study team at any point if outcomes appear 
unequivocally worse than standard of care, if unusual types or rates of complications occur, or if 
any other safety concerns arise.  An interim analysis will be performed in order to assess 
comparative outcomes following successful treatment of 20 subjects and determine whether to 
proceed with the remainder of the study.
Variables:
1. Surgical harvest technique will not be standardized between surgeons with the exception of 
requiring suprafascial harvest overlying the area to be grafted.
2. Donor site of split-thickness graft will be at surgeon discretion.
17. Utilization of purse string suture or other methods to narrow the flap donor site wound prior 
to grafting.
18. Decision to pursue secondary wound care strategy will be at surgeon discretion, including 
timing and type of treatment.
Funding Source and Funding Needs:
All Restrata products will be provided at no cost to patients by Acera Surgical Inc.  No additional
financial resources will be necessary to support this project.
Background Information:
Restrata (Acera Surgical, St. Louis, MO) is a synthetic hybrid-scale fiber matrix that possesses a 
fibrous structure of varying fiber diameters with high porosity [1]. The architecture of the 
material, which is similar to native extracellular matrix, allows for cell ingress and retention, as 
well as neovascularization of newly forming tissue, before completely degrading via hydrolysis 
[1]. The electrospun matrix is composed of two synthetic biocompatible polymers, polyglactin 
910 (PLGA 10:90) and polydioxanone (PDO), both of which are used in other (FDA)-cleared 
devices, including dura substitutes, resorbable sutures, and orthopedic implants [1]. PLGA 10:90 
and PDO were specifically selected in order to achieve a matrix with optimal handling properties
and a rate of resorption ideally matched to the process of new tissue formation and wound 
healing. These polymers are co-electrospun into soft, white, compliant, non-woven sheets 
capable of supporting the natural wound healing process [1]. Once applied to a wound, the 
matrix supports cellular infiltration, new tissue formation, and wound healing while 
progressively resorbing into the tissue over the course of two weeks, on average.
Multiple clinical studies, including retrospective analyses, prospective analyses, and case reports 
have been conducted to evaluate the clinical efficacy of the synthetic hybrid-scale fiber matrix 
across multiple use cases in the wound care setting. A summary of the clinical studies and 

outcomes can be found in the table below [2-17]. Assessment of over 150 treated wounds of 
varying etiologies demonstrated that significant wound healing was observed following 
treatment with the synthetic hybrid-scale fiber matrix across multiple wound types and clinical 
use settings. Results further demonstrate that the electrospun hybrid-scale fiber matrix also 
offered unique clinical versatility in facilitating both tissue granulation and a bridge to skin 
grafting as well as definitive wound closure and re-epithelialization, unlike alternative synthetic 
scaffolds and matrices.
Published rates of skin graft failure in forearm reconstruction range from 13-38% [18-20].  This 
occurrence prolongs healing, requires multiple additional health care encounters, and may result 
in worse aesthetic or event outcomes, sometimes requiring physical therapy.  Patients have 
multiple complex medical needs following head and neck free flap reconstruction, and 
improving forearm reconstructive outcomes would undoubtedly be beneficial in this setting.  
Wound care matrices have been investigated in forearm flap reconstruction.  Wester et al 
compared use of STSG alone to the combination of acellular dermal matrix Alloderm (Allergan, 
Madison, NJ) in combination with STSG [21].  They noted improved cosmesis, similar rates of 
graft failure, and no cases of secondary graft requirement in the Alloderm + STSG group.  Other 
studies have investigated use of matrices alone or in a staged fashion with grafting [22-25].  
Restrata has not previously been studied for this purpose, and in light of the positive outcomes in
other similar wounds, investigation of its application to this purpose is relevant.
Clinical
indication
# of
woun
ds
Patient
demographi
cs
Treatment
method
Outcomes
Adverse
events
Referenc
e  
Chronic 
wounds (DFUs,
VLUs, PUs, 
traumatic and 
postsurgical 
wounds, 
nonvenous 
vascular 
wounds, 
necrotic 
wounds)
82
48% male; 
average 
patient age 
72 years; 
average 
wound age 
36 weeks; 
average 
wound 
surface area 
3.4 cm2
Multiple 
applications of 
the synthetic 
hybrid-scale 
iber matrix as 
needed for up to 
12 weeks
85% complete 
wound closure 
at 12 weeks and
signiicant 
reduction in 
local 
inlammation
None
[2]
Recalcitrant 
neuropathic 
foot ulcers
4
100% male; 
patient age 
range 67-73 
years
Weekly, or as 
appropriate, 
treatment with 
synthetic hybrid-
scale iber 
matrix followed 
by adjunctive 
therapy
75% complete 
wound closure 
and successful 
limb 
preservation
None
[3]
DFUs
24
90% male; 
average 
patient age 
55 years; 
average 
ulcer 
duration 16 
weeks; 
average 
ulcer surface
area 4.4 cm2
Weekly, or as 
appropriate, 
treatment with 
synthetic hybrid-
scale iber 
matrix for up to 
12 weeks
75% complete 
wound closure 
at 12 weeks
None 
due to 
synthetic
matrix
[4]

Chronic 
wounds (DFU, 
VLU, PUs, 
Charcot foot 
deformity)
5
80% male; 
average 
patient age 
66 years; 
average 
ulcer 
duration 51 
months
Multiple 
applications of 
the synthetic 
hybrid-scale 
iber matrix as 
needed in 
conjunction with 
NPWT
Formation of 
granulation 
tissue, coverage
over exposed 
structures, and 
reduction in 
wound size
None
[5]
PUs
11
64% male; 
average 
patient age 
55 years;
Single 
application of 
synthetic hybrid-
scale iber 
matrix as a 
foundation for 
rotational skin 
lap
Successful 
granulation 
tissue formation
and preparation
of wound site 
for lap 
reconstruction, 
with eventual 
wound closure 
rate of 90.9%
None
[6]
Chronic 
wounds (DFUs,
VLUs)
23
60% male; 
average 
patient age 
68 years; 
average 
ulcer 
duration 16 
months
Weekly, or as 
appropriate, 
treatment with 
synthetic hybrid-
scale iber 
matrix
96% complete 
wound closure 
at 21 weeks
None 
due to 
synthetic
matrix
[7]
TMA wounds
20
85% male; 
average 
patient age 
62 years
10 wounds 
treated with 
synthetic hybrid-
scale iber 
matrix to 
augment closure
of the suture line
and 10 control 
nonaugmented 
wounds with 
standard 
primary closure
80% complete 
wound closure 
following 
treatment with 
synthetic 
matrix; reduced 
time to healing 
(18%), 
compared to 
control
Wound 
dehiscen
ce (5), 
limb loss 
(2)
[8]
Post-Mohs 
wounds
10
Patient age 
range 63-90 
years
Multiple 
applications of 
the synthetic 
hybrid-scale 
iber matrix as 
needed
Efective re-
epithelialization 
and wound 
closure with 
minimal 
scarring
Infection
(1)
[9]
Post-Mohs 
wounds
4
75% male; 
average 
patient age 
78 years; 
average 
ulcer surface
area 11.5 
cm2
Multiple 
applications of 
the synthetic 
hybrid-scale 
iber matrix as 
needed
100% complete 
wound closure 
in 8 weeks with 
no scars or skin 
deformities
None
[10]
Peroneal 
tendon healing
12
25% male; 
patient age 
range 18-75 
years
Peroneal tendon 
repair 
augmented with 
synthetic hybrid-
scale iber 
matrix
Signiicant 
reduction in 
pain and rapid 
return to normal
activity
None
[11]
Complex 
cutaneous 
wounds 
(calciphylaxis 
lesion, 
abdominal 
istula lesion, 
necrotizing 
fasciitis lesion)
3
67% male; 
patient age 
range 30-54 
years
Multiple 
applications of 
the synthetic 
hybrid-scale 
iber matrix as 
needed in 
conjunction with 
NPWT
Signiicant re-
epithelialization 
and healing of 
the wounds and 
economic cost 
savings
None
[12]

Traumatic 
crush injury 
wound
1
24-year-old 
male
Single 
application of 
synthetic hybrid-
scale iber 
matrix as a 
foundation for 
STSG
Successful 
granulation 
tissue formation
and preparation
of wound site 
for STSG
None
[13]
Chronic dorsal 
foot wound
1
53-year-old 
male
Multiple 
applications of 
the synthetic 
hybrid-scale 
iber matrix as 
needed
Rapid and 
sustained 
coverage of 
exposed 
tendons and 
progressive 
wound area 
reduction
None
[14]
DFU
1
66-year-old 
diabetic 
male; wound 
duration >1 
year
Multiple 
applications of 
the synthetic 
hybrid-scale 
iber matrix as 
needed
Complete 
wound closure
None
[15]
Complex lower 
extremity 
wounds 
(scleroderma 
wound, VLU, 
amputation 
wounds)
4
75% male; 
patient age 
range 44-74 
years
Multiple 
applications of 
the synthetic 
hybrid-scale 
iber matrix as 
needed, in 
conjunction with 
HBOT for 2 
wounds
75% complete 
wound closure
None
[16]
Traumatic and 
thermal burn
1
10-month-old
male
Single 
application of 
synthetic hybrid-
scale iber 
matrix
Complete 
wound closure
None
[17]
DFUs – diabetic foot ulcers; HBOT – hyperbaric oxygen therapy; NPWT – negative pressure 
wound therapy; PUs – pressure ulcers; STSG – split-thickness skin graft; TMA – transmetatarsal 
amputation; VLUs – venous leg ulcers.
 
 
 References: 
1.
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healing material? A review of current science and introduction of a synthetic 
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4.
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