RECONSTRUCTIVE

Fat Grafting and Adipose-Derived Regenerative

Cells in Burn Wound Healing and Scarring:
A Systematic Review of the Literature
Alexandra Condé-Green,
M.D.
Andrew A. Marano, B.A.
Edward S. Lee, M.D.
Tom Reisler, M.D.
Leigh Ann Price, M.D.
Stephen M. Milner,
M.B.B.S., B.D.S., D.Sc.
Mark S. Granick, M.D.
Baltimore, Md.; and Newark, N.J.
Background: There is an abundance of literature supporting the efficacy of
fat grafting in aesthetic and reconstructive cases. There has been a recent
emphasis on the regenerative capacity of adipose-derived stem cells and their
utility in the improvement of wound healing and scarring provided by their
cytokine and growth factor profiles. Despite the wealth of evidence supporting
their efficacy, little attention has been paid to their utility in burn treatment.
The authors’ purpose was to provide an analysis of the literature regarding the
use of fat grafting and regenerative cells in the treatment of burn wounds to
guide surgeons and scientists on their clinical use.
Methods: A systematic review of the literature was performed by a thorough
search of 12 terms using the PubMed, Medline, and Cochrane databases. Two
hundred forty-one articles were subject to evaluation by predetermined inclu-
sion and exclusion criteria.
Results: Six murine and 12 human studies were selected, including case-con-
trol studies, case series, and case reports. They describe histologic and clinical
effects of fat grafting and regenerative cell therapy, including improvements in
burn scar size and texture, enhanced angiogenesis, decreased inflammation,
alleviation of pain, and return of function.
Conclusions: There is a dearth of randomized controlled trials and quantitative
analysis supporting the efficacy of fat grafting and adipose regenerative cells
in burns. However, the subjective improvements in scars are encouraging. The
authors hope that this review will be a foundation for future studies and will
highlight the breadth of knowledge yet to be explored by this therapy. (Plast.
Reconstr. Surg. 137: 302, 2016.)
CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

A
utologous fat grafting is a commonly used
technique for treating volume and con-
tour defects in aesthetic and reconstruc-
tive surgery. First described in the early 1900s,
this procedure became popular in the late 1980s,
From the Division of Burn Surgery, Department of Plastic and
Reconstructive Surgery, Johns Hopkins University, School of
Medicine; and the Division of Plastic Surgery, Department of
General Surgery, Rutgers New Jersey Medical School.
Received for publication April 7, 2015; accepted August 27,
2015.
Presented at the Eighth International Workshop on Wound
Technology, in Paris, France, January 18 through 20,
2015; and the Fifth International Fat Grafting Forum, in
New Orleans, Louisiana, March 12 through 14. 2015.
Copyright © 2015 by the American Society of Plastic Surgeons
DOI: 10.1097/PRS.0000000000001918
when liposuction increased the availability of fat
stores and allowed surgeons to experiment with
the therapeutic potential of autologous fat.1
There has been a recent emphasis on not only
the filling capability of fat but also its regenera-
tive capacity.2 The stromal vascular fraction of
processed fat grafts contains multipotent stem
cells that express adipogenic, osteogenic, and
chondrogenic genes.3 Many studies have demon-
strated the angiogenic, immunomodulatory, and
Disclosure: The authors declare no conflicts of
interests with respect to the authorship and/or publica-
tion of this article. The authors received no financial
support for the research and/or authorship of this
article.

302 www.PRSJournal.com
Copyright © 2015 American Society of Plastic Surgeons. Unauthorized reproduction of this article is prohibited.
 Volume 137, Number 1 • Burn Wound Healing and Scarring
antiapoptotic capabilities of these cells, making
them a valuable and effective tool in restoring
devitalized tissue, as evidenced by their efficacy
in improving radiation-damaged skin.4,5 Adipose-
derived stem cells have also been shown to play a
role in antiaging6 and skin regeneration by form-
ing tissue consisting of hypodermis, dermis, and
epidermis.7 It is this regenerative capacity that is
of particular interest in burn wound therapy.
There is an abundance of literature support-
ing the efficacy of fat grafting in both aesthetic
and reconstructive cases. Recent studies have
shown the utility of adipose-derived stem cells in
the improvement of wound healing, describing
their ability to regenerate soft tissues and their
remodeling capacity provided by their unique
cytokine and growth factor profiles. Despite the
wealth of evidence supporting their efficacy in
wound healing, little attention has been paid to
their utility in the treatment of thermal injury.
The purpose of this study was to provide a thor-
ough analysis of the literature regarding the use
of fat grafting and adipose-derived stem cells in
the treatment of burn wounds to guide surgeons
and scientists on their clinical use in burn wound
healing and scar remodeling, and in pursuing fur-
ther investigation.
PATIENTS AND METHODS
The foundation for this review was a system-
atic method for finding and evaluating the lit-
erature on the efficacy of fat and adipose stem
cell therapy in the treatment of thermal injury.
A comprehensive search was conducted by two
independent reviewers in April of 2015 using the
following terms alone or in combination in the
PubMed, MEDLINE, and Cochrane databases:
“burn,” “fat grafting,” “fat transplant,” “fat har-
vesting,” “fat transfer,” “adipose stem cell,” “lipo-
filling,” “lipoinjection,” “lipotransfer,” “wound
healing,” and “scar treatment.” In addition, the
terms “exp burn/”and “exp adipose tissue/” were
used in MEDLINE to search all articles including
burn and adipose tissue exploded subheadings.
Because one of the authors is fluent in Portuguese
and French, filters were set to include all articles
in English, Portuguese, and French.
Prospective inclusion criteria were the use of
fat or adipose stem cell therapy and reporting of
the effects on wound healing when used as an
early intervention, the effects on scar formation
when used on an old wound, and the effects on
quality of life. Studies included were case-control
studies, case series, case reports, animal studies
Copyright © 2015 American Society of Plastic Surgeons. Unauthorized reproduction of this article is prohibited.
using human fat, animal studies using animal
fat, clinical trials, and randomized controlled tri-
als. Exclusion criteria were articles on fat graft-
ing for nonburn wounds, burn to a surface other
than skin (e.g., cornea, bone), fat transfer as part
of another graft (dermal grafts), and radiation
injury. Necessarily excluded were articles we were
not able to access and those in languages other
than English, Portuguese, and French.
A formal statistical analysis of the eligible
studies was not performed because of the meth-
odologic and clinical heterogeneity. A detailed
systematic review of the diverse outcomes was
undertaken instead.
RESULTS
The primary search yielded 544 articles. After
removal of duplicates, 241 of these were found to
be distinct. The titles of remaining articles were
screened for relevance, after which 75 abstracts
were reviewed according to our inclusion crite-
ria. The remaining 28 articles were read in their
entirety and their references scoured for articles
that escaped our primary search criteria. Of these,
12 were excluded based on predetermined crite-
ria, and the remaining 16, along with one article
that was discovered by review of references, were
included in this review (Fig. 1). Thus, we present a
total of 17 articles describing 18 studies, as one of
the articles described two distinct studies.8
Human Studies
Twelve human studies were selected, includ-
ing case control studies (n = 3), case series (n = 7),
and case reports (n = 2). Adipose tissue was har-
vested from one or multiple sites, including the
abdomen (n = 9), trochanteric region (n = 3),
inner thigh (n = 1), and medial knee (n = 1), and
discarded burn tissue (n = 1). Adipose tissue was
processed by high-speed centrifugation (n = 9)
and low-speed centrifugation (n = 2). Further
processing included mincing and processing for
adipose-derived stem cell isolation (n = 1), and
supplementation of fat with stromal vascular frac-
tion (n = 1) or platelet-rich plasma (n = 1).
Case-Control Studies
Bruno et al. conducted a study on 93 chronic
burns scars divided into two halves, where half
of each scar was treated with lipofilling and the
other half served as a control.9 Improved vascu-
larization of the dermal papillae and better colla-
gen organization were shown in scars treated with
lipofilling after 6 months. There was a statistically
303
 Plastic and Reconstructive Surgery • January 2016
Fig. 1. Flow diagram of the search and selection strategy of
included articles.
significant decrease in S100-positive cells on
immunohistochemistry, indicating that lipofill-
ing correlates with reduction of melanocytes in
the wounds. There was a decrease in Langerin-
positive cells, most likely resulting from efflux of
trapped cells secondary to loose connective tis-
sue. Increased visualization of Ki-67 in the basal
layer of lipofilled wounds indicated that there was
increased proliferation. A modified Vancouver
Scar Scale was used to provide objective clinical
evaluation of scars. Scores of 41 before treatment,
29 at 3 months, and 15 at 6 months were reported
(range, 5 to 50, with low numbers representing
close to normal skin).
Klinger et al. conducted two separate studies
described in one article8 (which is reflected in a
footnote in Table 1).10–24 The case-control study
evaluated scars of 20 randomly selected patients.
Each scar was treated half with fat and half with
saline injection and evaluated by the Patient and
Observer Scar Assessment Scale25 and Durom-
eter measurement for scar firmness. Significant
improvement of color, shape, thickness, and
304
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movement was seen as early as 3 months postop-
eratively in the fat-grafted side.
Gentile et al. compared fat grafts to fat-
enhanced grafts with stromal vascular fraction or
platelet-rich plasma in 30 patients with burn and
posttraumatic scars.10 In stromal vascular frac-
tion– and platelet-rich plasma–enhanced groups,
63 percent and 69 percent of wounds maintained
their volume after 1 year, respectively, compared
with 39 percent of the control group, indicating
less fat resorption in enhanced grafts.
The first case-control study9 was the strongest,
as clinical results following treatment with fat
grafting were corroborated by immunohistochem-
ical findings achieving statistical significance, and
clinical evaluation was double blinded. The sec-
ond case-control study8 showed objective statisti-
cally significant clinical findings in treated scars,
but there was no histologic confirmation. The
third study10 exposed three different preparation
techniques of fat grafting to scars and showed that
fat supplemented with stromal vascular fraction
or platelet-rich plasma achieved better contour
maintenance, with increased graft take. However,
they did not compare them to untreated controls
with no fat grafting.
Case Series
Klinger et al. reported improvement in mimic
features, skin texture, and skin thickness in three
burn patients with facial hypertrophic scars and
keloids after fat injection into the dermohypoder-
mal junction performed twice, 3 months apart.11
Although findings were not compared to controls
or subjected to statistical analysis, new collagen
deposition, increased vascularity, and dermal
hyperplasia were observed. Although the sample
size was small, the clinical results were corrobo-
rated with histologic findings.
Caviggioli et al. performed fat grafting in the
nipple-areola complex of 12 patients who specifi-
cally suffered burns to the chest.12 The average
nipple projection was 4.6 mm at 2 weeks, with
patients rating the results as excellent; and the
projection was 2.9 mm at 2 years, with the major-
ity rating the results as good. These were objec-
tive clinical findings with a good follow-up period;
however, there was no control, histologic report,
or statistical analysis.
Brongo et al. reported evidence of new collagen
deposition, angiogenesis, and dermal hyperplasia
in scars of 18 burned patients treated with lipo-
filling three times at 3-month interval.13 Improve-
ments in texture, softness, thickness, and color of
treated scars based on a questionnaire completed
 Volume 137, Number 1 • Burn Wound Healing and Scarring

Table 1. List of Articles Included in This Systematic Review According to Inclusion and Exclusion Criteria,
Stratified by Level of Evidence
Level of No. of Subjects
Reference Study Type Evidence or Burn Scars
Human studies (n = 12)
Bruno et al., 20139 Case-control III 93 burn scars
Klinger et al.. 20138* Case-control III 20 patients with scars†
Gentile et al., 201410 Case-control III 30 patients with scars†
Klinger et al., 200811 Case series IV 3 patients with burn scars
Caviggioli et al., 201012 Case series IV 12 patients with burn scars
Brongo et al., 201213 Case series IV 18 patients with burn scars
Viard et al., 201214 Case series IV 15 patients with burn scars
Klinger et al., 20138* Case series IV 376 patients with scars†
Keck et al., 201315 Case series IV 5 patients with burns
Piccolo et al., 201516 Case series IV 240 patients†
Caviggioli et al., 200817 Case report V 1 patient with burn scar
Khouri et al., 201318 Case reports V 5 patients with burn scars†
Murine studies (n = 6)
Sultan et al., 201219 Murine — 20 mice
Shokrgozar et al., 201220 Murine — 10 rats
Huang et al., 201421 Murine — 30 rats
Loder et al., 201422 Murine — 20 mice
Karimi et al., 201423 Murine — 30 mice
Atalay et al., 201424 Murine — 20 rats
*Two studies were part of the same article.
†Three studies included burns and other types of wounds (trauma, ulcers).

by patients, surgeons, and external observers 1 year
after treatment were reported. Clinical improve-
ment of scars was supported by histologic findings
with a good follow-up period, but there was no
control, and no statistical analysis was conducted.
Viard et al. treated 15 patients with postburn
facial scars that had an average of 7.5 operations
1 year before fat grafting.14 Patients received two
to three sessions. Subjective improvements in
mimic features, skin texture, and skin thickness
were reported without controls or statistical analy-
sis of the results.
The second study of the 2013 article of Klinger
et al. reported improvements in scar elasticity, skin
softening, and mobility in periarticular regions
of 376 patients with retractile and painful scars
treated with lipofilling.8 This was a large study
where subjective clinical findings were reported;
however, the authors did analyze a group of 20
patients that we mentioned above in the case-con-
trol study group.
Keck et al. harvested adipose tissue from dis-
carded burn tissue. It was spread on a bovine col-
lagen-elastin scaffold and applied on the fascia of
previously excised wounds covered with skin graft
in five patients.15 Ninety percent of the skin graft
was viable at postoperative day 10 in three patients.
Flow cytometry, microscopy, and AdipoRed
(Lonza, Walkersville, Md.) staining revealed that
adipose cells from debrided tissues were compa-
rable to abdominal fat in quantity, proliferative
capacity, and differentiation. This study lacked
controls, was limited in number of cases, but rep-
resents a novel technique with much potential.
Piccolo et al. described their 3-year experi-
ence using fat grafting in acute and subacute burn
wounds, and burn scars. They treated 240 patients
who presented with burn, vascular, or traumatic
injuries. For acute and subacute wounds, fat was
injected at 2- to 4-week intervals until a defini-
tive procedure such as skin graft or flap coverage
was performed. Subsequent scars were treated
at 3-month intervals. The authors reported sub-
jective improvements in wound healing, fibrosis,
and scar suppleness.16 This study was large, with
adequate follow-up, but lacked statistical analysis
and controls.
Case Reports
Caviggioli et al. reported lasting correction of
epiphora, xerophthalmia, and lagophthalmos, 1
year after performing fat grafting in one patient
with medial ectropion secondary to chemical
burn.17 Khouri et al. reported scar softening and
increased range of motion after performing lipofill-
ing and percutaneous aponeurotomy (transform-
ing a restrictive scar into a neomatrix scaffold into
which fat grafts can settle) in patients with retractile
scars of the upper extremity, hands, and chest sec-
ondary to burns, radiation therapy, and congenital
restriction bands.18 Five of the patients presented
scars from burns, with objective measurement of
functional improvement, but lacked controls.

305
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 Plastic and Reconstructive Surgery • January 2016
Murine Studies
Six murine studies assessing clinical and bio-
chemical outcomes of applying fat (n = 2) or adipose
stem cells (n = 4) to burn wounds were selected.
Subjects were delivered burn injury by contact with
a metal object submerged in hot water (n = 4) or by
direct exposure to hot water (n = 2). The injury was
located on a depilated dorsum (n = 5) or a hind paw
(n = 1). Adipose tissue was harvested from mice or
rats, as autografts (n = 5); or discarded human fat,
as a xenograft (n = 1).
Sultan et al. conducted a controlled study
describing the physical and biochemical effects of
human fat on burn scars of 20 mice, where they
injected saline in one half and fat in the other. Fat-
grafted mice expressed significantly elevated levels
of stromal cell–derived factor-1, vascular endothe-
lial growth factor, and CD31 expression (indica-
tive of greater vascularity), and wound remodeling
expressed by transforming growth factor-β and
matrix metalloproteinase-9, compared with con-
trols. They showed greater flux on laser Doppler
scanning and less fibrosis.19 This study was the
strongest murine study, as there were untreated
control animals, and objective and statistically sig-
nificant macroscopic and histologic evaluations.
Shokrgozar et al. supplemented collagen scaf-
folds with adipose-derived stem cells and showed epi-
dermal regeneration in burn wounds treated in 10
rats compared with controls.20 Wound surface area
and histopathologic findings with formation of der-
mis and epidermis on the scaffolds supplemented
with adipose-derived stem cells were reported; how-
ever, statistical analysis was not mentioned.
Huang et al. investigated the effects of autolo-
gous fat on burn-induced neuropathic pain in
30 rats.21 Rats that received fat grafting had
reduced burn-induced neuropathic mechanical
allodynia by suppression of phosphorylation of
p38 in microglial cells. The clinical and histologic
findings were statistically significant, and there
were untreated controls.
Loder et al. studied the effects of isolated
autologous adipose-derived stem cells, fat, adipose-
derived stem cells and fat, and phosphate-buffered
saline grafts on burns of 20 mice.22 There was a sig-
nificant decrease in wound surface area in all groups
compared to controls, but not to each other. Adi-
pose-derived stem cells and mixed groups showed
significant decrease in wound depth apoptosis.
Karimi et al. reported significant increases
in fibroplasia and collagen remodeling and a
decrease in surface area of wounds treated with
adipose-derived stem cells in comparison with
306
Copyright © 2015 American Society of Plastic Surgeons. Unauthorized reproduction of this article is prohibited.
fat grafts in 30 mice.23 The differences in eschar
thickness, inflammatory cell counts, epithelializa-
tion, and angiogenesis were not significant.
Atalay et al. showed statistically significant
decreased inflammation and fibroblastic prolifer-
ation, and increased vascular endothelial growth
factor expression, vascularization, and prolif-
erating cell nuclear antigen index (suggesting
improved wound healing) in acute burns of rats
injected with stromal vascular fraction.24 There
was no macroscopic evaluation of the wounds.
The first three murine studies were con-
ducted in burn scars,19–21 and the last three were
conducted in acute burns showing the effects of
fat and adipose regenerative cells on wound heal-
ing.22–24 The last two studies had histologic results
reported by pathologists that were blinded to
study groups (Tables 1 and 2).
DISCUSSION
Although limited in number, studies detailing
the use of fat grafts or adipose-derived regenera-
tive cells on burn wounds and scars have had posi-
tive results. Murine studies have suggested that fat
grafting therapy can enhance vascularity, promote
wound remodeling, and diminish neuropathic
pain when administered weeks after injury.19,21 Such
attributes are of particular utility when considering
the common features of burn wounds: hypertro-
phic scars are characterized by an overactive prolif-
erative phase and an impaired remodeling phase of
wound healing,26 and neuropathic pain may occur
in more than 50 percent of burn victims.27 Murine
studies have also suggested that adipose-derived
stem cell therapy may improve outcomes when
applied on a newly acquired burn wound. Although
some studies had conflicting results regarding the
effect on wound surface area, most concluded that
the early use of adipose-derived stem cell therapy
altered the course of the remodeling phase of heal-
ing through decreased apoptosis22 and increased
fibroplasia.23 Murine studies have limited applica-
bility in human treatment; however, the human
case-control studies, case series, and case reports
have corroborating results.
With regard to treatment of burn scars, histo-
logic analysis in human studies revealed that fat
grafting may increase vascularity, new collagen
deposition, and reorganization.9,11,13 Studies also
reported improvements in mimic features, skin
texture, thickness, color,11,13,14 and patient satisfac-
tion.11,12,14 The utility of lipofilling as a secondary
measure to improve previous treatments is also
considerable. Although the regenerative capacity
Copyright © 2015 American Society of Plastic Surgeons. Unauthorized reproduction of this article is prohibited.

Volume 137, Number 1 • Burn Wound Healing and Scarring

Table 2. Summary of Clinical, Macroscopic, and Microscopic Findings of Articles Reviewed, Including Advantages and Disadvantages of Each Study
Processing Acute Wounds Clinical/Macroscopic Microscopic
References Techniques vs. Scars Findings Findings Study Strengths Study Weaknesses
Human studies
Bruno et al., High-speed centrifugation Scars Functional and aesthetic Improved Comparison to controls No controls or
20139 improvement vascularization (half scar treated vs. half statistical significance
Increase patient of dermal papillae scar untreated) regarding objective
satisfaction score Better organization Double-blinded assessment clinical scores (Van-
of collagen of clinical evaluation couver Scar Scale and
Significant decrease Statistical significance for patient satisfaction
in S100-positive histology and IHC score)
cells and Langerin-Objective measurement of
positive cells clinical findings (Vancou-
ver Scar Scale) confirmed
by histologic findings
Adequate follow-up period
All scars resulted from burn
injury
Klinger et High-speed centrifugation Scars Pain relief, improved scar None reported Comparison to controls Scars resulting from vari-
al., 20138* elasticity, mimic features, (half scar injected with fat ous injuries (trauma,
mobility, filling of volume vs. half scar injected with after
deficits saline) surgery, radiotherapy,
Improved softness Randomized selection of burns)
(Durometer) patients
Improved POSAS Objective measurement of
clinical findings (POSAS
and Durometer)
Statistical significance for
clinical findings
Gentile et Three methods: Scars Restoration of contour No microscopic Comparison of multiple No comparison to
al., 201410 High-speed centrifugation Improved texture, softness evaluation of scars fat-processing techniques untreated controls
High speed centrifugation Improved patient satisfaction Objective measurement of Scars resulting from vari-
plus PRP contour maintenance by ous injuries (trauma
SVF enhancement MRI/ultrasound and burns)
Statistical significance of
clinical findings when
compared to nonen-
hanced fat grafting
Adequate follow-up
period (60 mo)
Klinger et High-speed centrifugation Scars Improved mimic features, New collagen One of the earliest Small sample size
al., 200811 skin texture, thickness deposition, studies showing (n = 3)
Soft-tissue contour increased local clinical improvement Lack of controls or
documented by MRI vascularity, dermal All scars resulted from statistical analysis
hyperplasia burn injury
Caviggioli et High-speed centrifugation Scars Improved nipple projection, None reported Objective measurement of Lack of controls or
al., 201012 skin texture, softness, clinical findings statistical analysis
color, elasticity Adequate follow-up (2 yr)
Improved patient satisfaction

(Continued )
307
 Table 2. Continued

308
Processing Acute Wounds Clinical/Macroscopic Microscopic
References Techniques vs. Scars Findings Findings Study Strengths Study Weaknesses
Brongo et Low-speed centrifugation Scars Improved texture, softness, New collagen deposi- All scars resulted from burn Lack of controls or
al., 201213 thickness, color tion, injury statistical analysis
Reduction of scar contrac- neoangiogenesis, Adequate follow-up period
ture dermal hyperplasia (15 mo)
Improved symptomatology Objective measurement
per questionnaire of clinical findings (by
means of questionnaire)
Viard et High-speed centrifugation Scars Improved mimic features, None reported All scars resulted from burn Lack of controls or
al., 201214 skin texture, thickness injury statistical analysis
Improved patient satisfaction Lack of objective
clinical evaluation
Klinger et High-speed centrifugation Scars Pain relief, improved scar None reported Large sample size (n = 376) Lack of controls or
al., 20128* elasticity, mimic features, Added small group of statistical analysis
mobility in periarticular 20 patients analyzed Lack of objective
scars objectively, with statistical clinical evaluation
analysis (shown above*) Scars resulting from vari-
ous injuries (trauma,
after
surgery, radiotherapy,
burns)
Keck et ASC isolation (from Acute burns Improved skin graft Histology showed Novel therapeutic Lack of controls
al., 201315 débrided burn skin) take (n = 3) débrided burn technique Small sample
fat comparable to Potential for patients size (n = 5)
abdominal fat with large burn surface
Adipose tissue area
detected in recon-
structed areas
Piccolo et High-speed Acute, suba- Improved wound healing, Increase in elastic Large sample size (n = 240) Lack of controls or
al., 201516 centrifugation cute burns, fibrosis, scar suppleness fibers Adequate follow-up (3-yr statistical analysis
and scars experience) Lack of objective
clinical evaluation
Scars resulting from vari-
ous injuries (trauma,
ulcers, burns)
Caviggioli et High-speed Scars Correction of functional None reported Adequate follow up (1 yr) Small sample size
al., 200817 centrifugation deficits in periorbital One of the earliest studies (n = 1)
region showing clinical Lack of objective
Improved skin texture, improvement clinical evaluation
softness, elasticity
Khouri et Low-speed Scars Softened scar, increase None reported Objective measurement of Small sample size
al., 201318 centrifugation mobility, texture functional improvement (n = 5)
Lack of controls

(Continued )
Plastic and Reconstructive Surgery • January 2016

Copyright © 2015 American Society of Plastic Surgeons. Unauthorized reproduction of this article is prohibited.
Copyright © 2015 American Society of Plastic Surgeons. Unauthorized reproduction of this article is prohibited.

Volume 137, Number 1 • Burn Wound Healing and Scarring

Table 2. Continued
Processing Acute Wounds Clinical/Macroscopic Microscopic
References Techniques vs. Scars Findings Findings Study Strengths Study Weaknesses
Murine studies
Sultan et al., High-speed Scars Improved color, texture Increase CD31+ cells, Comparison to untreated
201219 centrifugation Greater flux by means of Picrosirius Red control animals
Doppler staining Objective macroscopic
Increased SDF-1, evaluation
VEGF, TGF-β, and Statistical significance for
MMP9 macroscopic and histo-
logic findings
Shokrgozar et ASC isolation Scars Improved wound Increased epidermal Comparison to untreated Lack of statistical
al., 201220 surface area regeneration controls analysis
Objective macroscopic
evaluation
Huang et al., Mechanical mincing Scars Decreased force Decreased p38+ and Comparison to untreated
201421 required to produce OX42+ cells controls
mechanical allodynia Increased collagen Objective macroscopic
deposition, evaluation
decreased cellu- Statistical significance for
larity clinical and histologic
findings
Loder et al., High-speed centrifugation Acute burns Decreased wound Decreased caspase Comparison of ASC, fat
201422 High speed centrifugation surface area staining and graft, fat plus ASC, and
plus ASC (all treatment groups) increased CD31 untreated controls
ASC Decreased wound (ASC and mixed Objective macroscopic
depth (ASC and groups) evaluation
mixed groups) Statistical significance for
macroscopic and histo-
logic findings
Karimi et al., Washing plus low- Acute burns Decreased wound surface Significantly Comparison of ASC, fat Lack statistical
201423 speed centrifugation area for ASC group increased fibro- graft, and untreated significance for
ASC (not significant) plasia, collagen controls macroscopic
remodeling Pathologist blinded to study findings
groups
Objective macroscopic
evaluation
Statistical significance for
histologic findings
Atalay et al., SVF isolation Acute burns None reported Decreased inflamma- Comparison to untreated Lack objective
201424 tion, fibroblastic controls macroscopic
proliferation, Pathologist blinded to study evaluation
increased groups
vascularization Statistical significance for
Increased PCNA histologic findings
index (wound
healing), VEGF
expression
IHC, immunohistochemistry; POSAS, Patient and Observer Scar Assessment Scale; PRP, platelet-rich plasma; SVF, stromal vascular fraction; MRI, magnetic resonance imaging; ASC, adipose-
derived stem cells; SDF-1, stromal cell–derived factor 1; TGF-β, transforming growth factor-β; VEGF, vascular endothelial growth factor; MMP9, matrix metalloproteinase 9; PCNA, proliferating
cell nuclear antigen.
309

*Two studies were part of the same article.

 Plastic and Reconstructive Surgery • January 2016

Fig. 2. Effects of fat grafting and adipose-derived regenerative cells on burn wounds and scars. VEGF, vascular endothelial growth
factor; SDF-1, stromal cell–derived factor 1; TGF-β, transforming growth factor-β; MMP-9, matrix metalloproteinase 9.

of adipose-derived stem cells is an alluring con-
cept,28,29 there are notably few human studies
detailing the use of adipose-derived stem cell–
supplemented grafts in burns.10,15
There were two human studies that investi-
gated wound healing in its acute phase. The large
series studied by Piccolo et al.16 showed improved
wound healing and fibrosis in acute and subacute
wounds. Although there was lack of controls, this
article had pertinent details on the procedure,
and adequate follow-up. The case series using
adipose cells from discarded burned tissue15 was
a small case series that was difficult to assess, but
these cells were shown to share the adipogenic,
osteogenic, and chondrogenic potential of their
abdominally derived counterparts.30–32 Therefore,
they may represent a source of multipotent cells in
patients with extensive burns, for whom there may
not be enough viable tissue to perform subcutane-
ous liposuction to obtain such cells from nonin-
jured sites. Indeed, as the percentage of total body
surface area affected by burn injury increases, so
does the availability of these adipose-derived stem
cells from discarded burn tissue.
Adipose-derived regenerative cells have been
used in the treatment of other burn sequelae such
as heterotopic ossification.33 These studies were
not included, as we focused on the effects on burn
wounds.
Although nearly all documented uses of this
therapy on burn wounds have had positive results,
it should be noted that much of the current litera-
ture consists of case reports or case series that lack
rigorous statistical analysis (only two human stud-
ies included statistical analysis) or power. There
has yet to be a large, prospective, randomized,
controlled study detailing its use in patients with
burn wounds and scars.
We have attempted to summarize all articles
relevant to this subject. Our inclusion criteria
were necessarily broad and our search terms were
diverse, and we included articles in languages
other than English. Still, we may have missed
studies that have been undertaken with the use

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Copyright © 2015 American Society of Plastic Surgeons. Unauthorized reproduction of this article is prohibited.
 Volume 137, Number 1 • Burn Wound Healing and Scarring
of fat grafting and burns. Even so, the results are
encouraging. Reports of clinical and histologic
improvements highlight the potential of this
therapy (Fig. 2), and show that much is yet to be
explored in this field.
CONCLUSIONS
After careful review of the literature regarding
the utility of fat grafting and adipose-derived regen-
erative cells in the treatment of burns, it is apparent
that this therapy has many documented benefits.
Murine studies have shown histologic improve-
ments in angiogenesis, collagen organization, and
neuropathic pain. Human studies have shown
similar biochemical effects in addition to improve-
ments in clinical features such as skin texture, soft-
ness, coloration, and function, bearing in mind
that the human experience is anecdotal and the
laboratory experiences are questionable because of
experimental design and number of subjects. This
review suggests that, at this time, there is no signifi-
cant literature to suggest that fat grafting in acute
burn wounds facilitates wound healing and ame-
liorates subsequent scarring. There is substantial
evidence that fat grafting in burn scars is helpful
in modifying scar tissue. There is a dearth of ran-
domized controlled trials and quantitative analysis
supporting the efficacy of fat and adipose-derived
stem cells in burns. However, this emerging ther-
apy is encouraging. It is our hope that this review
will be a foundation for future studies and high-
light the breadth of knowledge yet to be explored
by this therapy.
Alexandra Condé-Green, M.D.
Division of Plastic Surgery
Department of General Surgery
Rutgers New Jersey Medical School
Newark, N.J. 07103
acondegreen@yahoo.com
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