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Abstract and Figures

Background For decades, facial fat grafting is used in clinical practice for volume restoration. The main challenge of this technique is the variable volume retention. Over the past years, studies reported the addition of supplements to augment the fat graft to increase volume retention. Objectives The aim of this systematic review was to investigate which supplements increase volume retention in facial fat grafting as assessed with volumetric outcomes and patient satisfaction. Methods Central, MEDLINE, EMBASE, Web of Science Core Collection and Google Scholar were searched until 30th of November 2020. Only studies assessing volume after facial fat grafting with supplementation in human subjects were included. Outcomes of interest were volume or patient satisfaction. Quality of the studies was assessed using the Effective Public Health Practice Project tool. Results After duplicates were removed 3724 studies were screened by title and abstract. After reading 95 full-text articles, 27 studies were eligible and included for comparison. Supplementation comprised of platelet rich plasma (PRP), platelet rich fibrin, adipose tissue-derived stromal cells or bone marrow-derived stromal cells, cellular or tissue stromal vascular fraction (SVF) or nanofat. In 13 out of 22 studies the supplemented group showed improved volumetric retention and 5 out of 16 studies showed greater satisfaction. The scientific quality of the studies was rated as weak for 20 of 27 studies, moderate for 6 of 27 studies and strong for 1 study. Conclusions Our results show that it remains unclear if additives contribute to facial fat graft retention while there is a need to standardize methodology.
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Facial Surgery
https://doi.org/10.1093/asj/sjac122
www.aestheticsurgeryjournal.com
University of Groningen, Groningen, the Netherlands. Dr Dijkstra
is a professor, Department of Rehabilitation Medicine, University
Medical Center Groningen, University of Groningen, Groningen, the
Netherlands.
Corresponding Author:
Dr Martin C.Harmsen, Department of Pathology and Medical Biology,
University of Groningen, University Medical Center Groningen,
Hanzeplein 1-EA11, 9713 GZ Groningen, the Netherlands.
E-mail: m.c.harmsen@umcg.nl
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Review Article
Supplementation of Facial Fat Grafting to
Increase Volume Retention: ASystematic
Review
JanAartM.Schipper, MD ; LindaVriend, MD ; AartjeJ.Tuin, MD, DMD,
PhD; PieterU.Dijkstra, PT, MT, PhD; RutgerH.Schepers, MD, DMD,
MSc, PhD; BerendvanderLei, MD, PhD; JohanJansma, MD, DMD,
MSc, PhD, FEBOMFS; and MartinC.Harmsen, PhD
Abstract
Background: For decades, facial fat grafting has been used in clinical practice for volume restoration. The main challenge
of this technique is variable volume retention. The addition of supplements to augment fat grafts and increase volume re-
tention has been reported in recent years.
Objectives: The aim of this systematic review was to investigate which supplements increase volume retention in facial
fat grafting as assessed by volumetric outcomes and patient satisfaction.
Methods: Embase, Medline, Ovid, Web of Science Core Collection, Cochrane Central Register of Controlled Trials, and
Google Scholarwere searched up to November 30, 2020. Only studies assessing volume after facial fat grafting with sup-
plementation in human subjects were included. Outcomes of interest were volume or patient satisfaction. The quality of
the studies was assessed with the Eective Public Health Practice Project tool.
Results: After duplicates were removed 3724 studies were screened by title and abstract. After reading 95 full-text articles, 27
studies were eligible and included for comparison. Supplementation comprised of platelet-rich plasma, platelet-rich fibrin, adipose
tissue–derived stromal cells or bone marrow–derived stromal cells, cellular or tissue stromal vascular fraction, or nanofat. In 13 out
of 22 studies the supplemented group showed improved volumetric retention and 5 out of 16 studies showed greater satisfaction.
The scientific quality of the studies was rated as weak for 20 of 27 studies, moderate for 6 of 27 studies, and strong for 1 study.
Conclusions: It remains unclear if additives contribute to facial fat graft retention and there is a need to standardize
methodology.
Level of Evidence: 4
Editorial Decision date: May 5, 2022; online publish-ahead-of-print May 16, 2022.
© 2022 The Aesthetic Society.
Dr Schipper is a medical doctor and Dr Harmsen is a professor of
cardiovascular regenerative medicine, Department of Pathology and
Medical Biology, University of Groningen, University Medical Center
Groningen, Groningen, the Netherlands. Dr Tuin is an oral and
maxillofacial surgeon in training and Drs Schepers and Jansma are
oral and maxillofacial surgeons, Department of Oral and Maxillofacial
Surgery, University Medical Center Groningen, University of
Groningen, Groningen, the Netherlands. Dr Vriend is a medical
doctor and Dr van der Lei is a professor, Department of Plastic
and Reconstructive Surgery, University Medical Center Groningen,
This is an Open Access article distrib-
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Commons Attribution-NonCommercial
License (https://creativecommons.org/
licenses/by-nc/4.0/), which permits
non-commercial re-use, distribution, and
reproduction in any medium, provided
the original work is properly cited. For
commercial re-use, please contact jour-
nals.permissions@oup.com
Facial Surgery
Aesthetic Surgery Journal
2022, 1–17
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Fat grafting has been performed in clinical practice since
the end of the 19th century.1 It has been used to restore
volume loss due to trauma, aging, congenital defects, or for
aesthetic reasons, predominantly in the face, breasts, and
buttock. Facial fat grafting can be performed easily, safely,
and with minimum donor-site morbidity and complications.2
However, not all transplanted tissue is retained at the ac-
ceptor site. Long-term volume retention rates vary widely
between 25% and 80%.3-5 Additionally, multiple surgical
procedures are often required to obtain the desiredvolume.
Lipografting is a form of tissue transplantation, albeit
of fragmented adipose tissue. These fragments consist
of multiple large lipid-laden adipocytes that are structur-
ally supported by connective tissue and perfused with a
highly developed microvasculature. Adipocytes are about
4-fold less numerous than stromal vascular cells, yet com-
prise about 90% of the total volume of fat.6 Upon trans-
plantation (ie, fat grafting), the survival and regeneration
of adipocytes are pivotal to retaining the grafted volume.7
Ischemia may cause apoptotic loss of adipocytes, and thus
suppression of apoptosis in fat grafts might improve graft
volume retention. For graft survival, it is essential to form
a rapid connection between local vasculature and capil-
laries that literally stick out from the tissue clumps in the
fat graft. Thus angiogenic stimulation by fat graft supple-
ments is warranted. Any adipocytes lost from ischemic
insult require replenishment through proliferation of pre-
adipocytes (adipose tissue–derived stromal cells [ASCs])
and their dierentiation and maturation into adipocytes,
which would be supported by promitogenic factors in sup-
plements. Finally, metabolic maintenance is important be-
cause adipocyte volume, ie, the storage of the high-energy
triglycerides, varies with the body’s metabolic demand.
Weight loss is associated with loss of adipocyte volume
and consequently with reduced graft volume.8 Although
repeated fat grafting does build up sucient volume, this
is an undesirable burden for the patient. Therefore, sup-
plements that augment suppression of apoptosis, stimu-
late proliferation, and enhance angiogenesis are desired.
In clinical applications, the cellular fate of grafted fat is usu-
ally not assessed, yet this does not preclude investigation
of the influence of supplements on graftvolume.
To increase graft retention, supplementation with sev-
eral autologous components has been investigated.
Blood-derived products, eg, platelet-rich plasma (PRP) and
platelet-rich fibrin (PRF),9,10 are a source of concentrated
platelets, growth factors, and cytokines which could in-
duce better graft retention by promoting angiogenesis
and reducing apoptosis.11 Adipose tissue–derived com-
ponents, eg, ASCs, cellular and tissue stromal vascular
fraction (cSVF, tSVF),12,13 and nano- and microfat,14-16 have
shown proangiogenic action through paracrine factors
which could induce better graft vascularization, reduce
apoptosis, and increase proliferation.17,18 Furthermore,
enzymatic cell-assisted lipografting made addition of cSVF
or cultured ASC to fat grafting popular.4, 19-20 However, be-
cause cell-assisted lipografting requires enzymatic diges-
tion of SVF and the use of animal-derived enzymes such
as collagenase it is restricted by legislation in many coun-
tries,21 and hence new nonenzymatic, fast, intraoperative,
mechanical dissociation procedures have been developed
to produce tSVF.22,23 PRP or PRF are also easily obtained
by centrifugation of blood with or without anticoagulant.24
These supplementations are believed to improve retention
through either increased survival of the grafted cells by re-
ducing/preventing cell apoptosis, or by restoring hyper-
trophy or increasing vascularization at the injectionsite.
Currently, the number of clinical studies investigating
supplemented fat grafting is increasing rapidly, and multiple
new supplementation therapies are being developed.25
These developments warrant systematic evaluation of the
clinical available evidence. The current systematic reviews
on fat graft supplementation are heterogeneous because
they include human and animal studies for various indi-
cations.26,27 The aim of this systematic review was there-
fore to investigate the ecacy of human facial fat grafting
based on quantitative volumetric outcome measures and
patient satisfaction assessments.
METHODS
Protocol and Registration
This manuscript follows the Preferred Reporting Items for
Systematic Reviews and Meta-analysis (PRISMA) state-
ment.28 The study was registered in Prospero (register
code: CRD42020179975).
Search Strategy and Information Sources
A systematic literature search was conducted in the elec-
tronic medical databases Embase (Elsevier, Amsterdam,
the Netherlands), MEDLINE (National Library of
Medicine, Bethesda, MD), Ovid (Wolters Kluwer, Alphen
aan den Rijn, the Netherlands), Web of Science Core
Collection (Clarivate Analytics, London, UK), Cochrane
Central Register of Controlled Trials (CENTER; London,
UK), and Google Scholar (Google, Mountain View, CA)
from inception to November 30, 2020. Search strategy
was based on the PICO (population, intervention, com-
parison, outcome) framework and combined terms related
to fat graft transplantation (ie, lipofilling, fat transplantation,
adipose tissue transplantation, adipose tissue grafting,
volume retention) plus a supplementation therapy (ie, PRP,
ASCs, SVF, nanofat, microfat).29 In databases where a the-
saurus was available (Embase and MEDLINE), papers were
searched by thesaurus terms and by title and/or abstract.
2 Aesthetic Surgery Journal
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Schipper et al 3
The searches were adapted corresponding to each data-
base (Supplemental Table 1, available online at www.
aestheticsurgeryjournal.com, and Figure 1). Reference
lists of included studies were analyzed to identify relevant
studies missed in the searches.
Eligibility Criteria
Studies were included if they clinically evaluated the
effects of fat grafting in combination with a supple-
ment, for instance the addition of PRP, ASCs, or SVF,
on volume restoration in the face or patient satisfac-
tion. Only studies injecting in the adipose tissue plane
in the face were included. Studies were excluded when
no volumetric outcome was reported, as were studies
reporting on other body parts than the face only. If
studies described multiple body parts and data of
the face were separately described, the study was in-
cluded. (Systematic) reviews, case studies, conference
abstracts, letters to the editor, and animal and in vitro
studies were also excluded. No publication date restric-
tion was applied.
Study Selection and Data
Collection Process
Two reviewers (J.S., L.V.) independently assessed titles,
abstracts, and full texts. Disagreement between reviewers
was discussed until consensus was reached. In the case
of persistent disagreement, a senior author (M.H.) gave a
binding verdict.
Data Extraction
All data were extracted by the same 2 reviewers and con-
sisted of 5 categories: study characteristics, treatment
characteristics, complications, volumetric assessment of
fat graft (retention), and patient satisfaction.
Complications were categorized as minor (erythema,
mild edema, hematoma, local pain at incision site, and
oily cyst) and major complications (infection, tissue loss,
skin necrosis, fibrosis, severe edema, pain spreading
beyond injection site, cellulitis, fat embolus, and em-
bolus causing blindness). For supplemented fat grafting
therapy, data outcomes of interest were time between
harvesting and injection, injected volumes, supplement
dosing, cell yield or PRP concentration, isolation pro-
cedures, repeated treatments, and characterization of
supplementation therapy. For volumetric outcomes, data
from objective and subjective volume measurement
tools and follow-up points were extracted. When studies
reported fat graft resorption as an outcome measure, re-
tention was calculated as inverse resorption (100% – x%).
For each volume retention reported, a fold-change was
calculated (%supplemented fat divided by % fat). A dif-
ference was reported when there was a statistically sig-
nificant dierence (P < 0.05).
Risk of Bias in Individual Studies
The 2 reviewers independently assessed risk of bias with
the Eective Public Health Practice Project tool (EPHPP).30
This tool enables quality assessment of dierent types of
Figure 1. Flow diagram of study selection.
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study design. Studies were given an overall final rating as
strong, moderate, or weak based on ratings of study design,
selection bias, confounders, data blinding, data collection,
and dropouts. According to the EPHPP tool, “strong studies”
had no weak rating, “moderate studies” had 1 weak rating
and “weak studies” had 2 or more weak ratings.
RESULTS
Study Selection
In total, 3724 studies were identified. After title and abstract
screening, 95 studies remained for full-text assessment of
eligibility criteria (Figure 1). A total of 27 studies were in-
cluded; 68 studies were excluded for the following reasons:
10 studies were excluded because the fat graft was not sup-
plemented;
23,31-39 19 studies were excluded because fat graft
retention was not assessed by volumetric or patient satisfac-
tion measurements;
40-59 3 studies were excluded because
the study methods or intervention were not evaluable due
to insucient description;
60-62 8 studies were excluded be-
cause these were conference abstracts;
63-69 13 studies were
excluded because these concerned trial registrations;
70-82 1
study was excluded because the supplementation therapy
was not carried out in the face, but in other body parts;
83 in
1 study the injection site was not adipose tissue but product
was injected within the muscles of the face (facial muscular
plane);
84 12 studies were excluded because they did not de-
scribe human subjects or clinical results;
85-95 no translation
of 1 study was available (Russian).96
Study Characteristics
The studies included were published between 2008 and
2020 (Table 1). Follow up ranged from 6 to 60months and
a total of 1117 participants were described in the studies
(range, 6 to 236 per study). The mean age of the partici-
pants ranged between 6 and 61.5years old and 73% of
all patients were female (range, 33%-100%). Five studies
had a female sex bias due to the inclusion of female parti-
cipants only.97-101 Eight studies reported mean BMI, which
ranged from 17 to 32kg/m². Indications for supplemented
fat grafting were with underlying pathology (48%) or cos-
metic (without underlying pathology) with (19%) or without
facelift (33%). Indications with underlying pathology
were craniofacial deformity (31%), scars (23%), (hemi)fa-
cial lipoatrophy (15%), Parry-Romberg syndrome (15%),
or a combination of these indications (15%). The majority
(13/27) of the studies supplemented fat grafts with PRP/
PRF. Three studies reported multiple supplements.102-104
Studies were categorized by type of supplement (PRP,
SVF, and cellular components) for analysis of supplement
characteristics, volumetric, and patient satisfaction out-
comes (Supplemental Table 2, available online at www.
aestheticsurgeryjournal.com, and Tables 2, 3).
Study Design and Quality
Study designs included randomized controlled trials
(n = 6),67,99,101,105-107 controlled trials (n = 6),4,19,108-111 cohort
studies (2 groups with pre- and posttreatment evalu-
ation, n = 6),34,103,104,108,112,113 cohort studies (1 group with
pre- and posttreatment evaluation, n = 8)98,100,114-119 and a
retrospective study (n = 1)45 (Table 4). Confounding factors
were not controlled for in 8 studies.42,44,108,110,114,116-118 The
reliability and validity of outcome measurements were
weak in 12 studies.4,19,44,67,105,108,110,113-116,119 Four studies re-
ported dropouts and reported the number of participants
who completed the follow up.101,105,107,118 Based on the
EPHPP guidelines, 20 studies had an overall final rating
of weak, 6 studies were rated as moderate, and only 1
study was rated as strong (4%).106 Data pooling and meta-
analysis was not possible due to heterogeneity across
studies in terms of clinical features, eg, population char-
acteristics, indications, supplementation strategies, and
additional interventions (facelift, additional injections), and
methodologic characteristics, eg, assessment tools, study
design, and followup.
Characteristics of Supplementation
Strategies
The mean injected total volume ranged from 6.8 to
100mL. The volume-to-volume ratio of PRP-to-fat ranged
from 1:2 to 1:9. In SVF-supplemented therapies, 2 out of 14
studies reported the ratio of supplementation. Repeated
supplemented fat graft injections were performed in 11
studies and concerned merely supplementation with
SVF and cellular components.19,34,108-113,115,117,118 Aminority
of studies reported supplement concentrations: platelet
concentration in PRP or PRF was 0.8 × 109 to 3.6 × 109/
mL (mean [standard deviation], 2.6 [1.3] × 109/mL), and the
number of nucleated cells in cSVF or tSVF was 0.3 × 105
to 100 × 105 cells.112,107,109 Some studies reported a con-
centration range of fat-supplemented therapy and the
single addition of bone marrow–derived stromal cells
(BMSCs) ranged from 3 to 86 × 108 at a volume ratio
of 2:1 of BMSC:fat graft.113 Most studies performed
intraoperative isolation procedures of the supplemen-
tation therapy. Two studies cultured ASCs for 14days109
and 14 to 28days34 before supplementing fat grafts but
the volume ratio was not reported.34,109 Only 4 studies re-
ported the lag time between preparation of supplements
to administration to the patient or the time (range) to pre-
pare the supplements.106,108-110 Three studies described
the characterization of supplements; nanofat plus PRF,
ASCs, cSVF.19,106,109 The shared joint analyzed markers in-
cluded expression of mesenchymal cell markers (CD73,
CD90, and CD105) albeit that these are not restricted
to mesenchyme, integrin β1 (CD29), and the absence of
leukocyte markers (CD45).
4 Aesthetic Surgery Journal
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Schipper et al 5
Table 1. Study Characteristics
Author
(year)
Design Follow up
(months)
Indication Pathologya Injection
site
Total
(n)
Ageb
(years)
Female
(n)
BMI
(kg/m2)
Comorbidities Intervention
(fat +)
Intervention
(n)
Control Control
(n)
Minor
complications
Major
complica-
tions
Bashir et al
2019
C2G 6 UP Hemifacial at-
rophy, craniofa-
cial microsomia,
posttraumatic
and postinfective
deformity
NR 37 24.9 [8.1] 28 NR NR cASC 16 Fat 21 “Most patients” Both in
control and
intervention
group: 6%
cellulitis
Bernardini
et al 2015
C1G 12 C + FL Brows,
upper
sulcus,
inferior orbit
hollow, tear
trough,
perioral
area, malar
and
zygomatic
areas, lips,
chin,
temporal
fossa
98 51 92 NR NR PRP 98 4% 3% of patients
oil cyst, 1 case
requiring
surgical
removal
Castro-Govea
et al 2018
C1G 18 UP Craniosynostosis Forehead 12 6 8 NR NR cSVF 12 0 0
Cervelli et al
2009
RC 18 UP Scars,
Parry-Romberg,
hemifacial
atrophy,
mandibular cyst
Zygomatic
region,
cheek,
buccal rim,
upper and
lower eyelid,
temporal
area, orbital
area
25 NR NR NR Diabetes,
hypertension,
nasal polypus,
neurologic
disease,
arteriopathy,
cardiologic
disease,
dislipidemy,
trauma
PRP 19 Fat 10 0 0
Chang et al
2013
CCT 18 UP Hemifacial
atrophy
NR 20 27.5 12 NR cSVF 10 Fat 10 0 0
Fontdevila et
al 2014
RCT 12 UP HIV lipoatrophy Cheeks 49 46.3 [7.4] 16 24.3 [3.2] Diabetes,
hypertension,
hypercho-
lesterolemia,
hypertrigly-
ceridemia,
fibrates/statin/
antidepres-
sant/
anxiolytic/
antidiabetic
drug use
PRP 20 Fat 29 0 0
Gennai et al
2017
C1G 6 C + FL Periocular,
perioral
area
65 49.7 58 NR NR PRP 65 0 0
Gentile et al
2014
C2G 12 UP Burns,
posttraumatic
scars
NR 20 NR 10 NR NR cSVFPRP 1010 Fat 10 0 0
Gentile et al
2020
C2G 60 C Zygomatic/
cheek
region,
lower
orbital area,
nasolabial
fold, lips
63 42.1d63 27 (21-
33.16)
tSVF 33 Fat 30 Intervention
group: 9%;
control group:
13%
0
Gu et al 2018 C1G 6 UP Scars NR 20 (25
scars)
38.3 14 NR tSVF 25 NR NR
Hesamirostami
et al 2019
C1G 30 C Forehead 56 40.2 52 NR NR PRP 56 0 0
Jianhui et al
2014
C2G 12 UP Parry-Romberg NR 36 24.3 [6.6]d25 NR NR Intra-
operative
BMSC
10 Fat 26 0 0
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Author
(year)
Design Follow up
(months)
Indication Pathologya Injection
site
Total
(n)
Ageb
(years)
Female
(n)
BMI
(kg/m2)
Comorbidities Intervention
(fat +)
Intervention
(n)
Control Control
(n)
Minor
complications
Major
complica-
tions
Keyhan et al
2013
RCT c12 C Cheek,
cheekbone
area
25 45 17 NR PRP 25cFat/PRF 25c0 0
Koh et al 2012 CCT 15 UP Parry-Romberg NR 10 28 5 NR cASC 5 Fat 5 0 0
Lee et al 2012 C1G c11 C + FL Malar
eminence,
infraorbital
region,
nasolabial
fold
9 43.3 6 NR NR cSVF 9cFat 9c0 0
Li et al 2013 C2G 6 NRG Temporal,
cheek, facial
asymmetry
38 29.4 [6.6]d38 NR NR cSVF 26 Fat 12 “Most patients” 0
Ozer et al
2019
C1G 9 C NR 14 44.9 [11.9] 14 NR NR PRP 14 0 0
Sasaki et al
2015
C2G 12 C + FL Midface 236 61.5d227 22.2 (16.9-
32.3)d
PRP
cSVF
cSVF/PRP
106
929
Fat 92 “All patients” 0
Sasaki et al
2019
RCT c12 C + FL Midface 10 54.4 10 22.4 (20.5-
24.6)
PRP 10cFat/sa-
line
10c“All patients” 0
Schendel et al
2015
C1G 17 C Temples,
malar areas,
forehead/
glabella,
eyelid area,
lips, chin
10 51.6 [9.6] 10 NR NR cSVF 10 0 0
Sterodimas et
al 2011
CCT 18 UP Several
congenital or
acquired facial
tissue defects
NR 20 45.1d10 21.6dSmoking,
hypertension,
diabetes,
COPD
cSVF 10 Fat 10 “Most patients” Control
group: 10%
infection
Tanikawa et al
2013
RCT 6 UP Craniofacial
microsomia
NR 14 15.4 [5.6]d9 <25 NR cSVF 7 Fat 7 “All patients” 0
Tenna 2017 CCT 6 UP Acne scars Cheeks 30 NR NR NR Fat/PRP/
laser
15 Fat/PRP 15 NR NR
Wei et al 2017 CCT 24 C Tempora,
geisoma,
frontal part,
palpebra
sup inf,
lacrimal
groove,
zygoma,
cheeks,
nasolabial
groove,
chin, mari-
onette lines,
submaxilla
139 28.5 NR NR NR Nanofat/PRF 62 Fat 77 0 0
Willemsen et
al 2018
RCT 12 C Temporal,
midface,
nasolabial
fold,
marionette
lines,
prejowling,
chin
25 52.1 [6.8] 32 (20-25) NR PRP 13 Fat/sa-
line
12 0 0
Yin et al 2020 RCT 50 C Forehead,
temporal,
cheek/
zygomatic,
nasolabial
fold
50 35.4 [8.2]d50 21.4 [1.9]d cSVF 25 Fat 25 0 0
Table 1. Continued
6 Aesthetic Surgery Journal
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Schipper et al 7
Influence of Supplementation Therapies
on Fat Graft Retention
Twenty studies assessed volume retention of sup-
plemented fat grafts after 3 to 36months, of which 3
studies reported multiple supplementation groups
(PRP/cSVF, PRP/cSVF/PRP + cSVF, PRP/tSVF).102-104
Volume was measured by computed tomography (CT),
MRI, 3-dimensional (3D) surface imaging, ultrasound,
visual 2D photograph assessment, numeric rating scale
(NRS), or Likert scale. Seven studies used 3D surface
imaging to assess fat graft retention. Volume measure-
ment methods were often not validated and details of
volumetric measurements were often not described,
or described too briefly to allow for reproduction of
studies.
Out of the 9 studies in which the graft was sup-
plemented with PRP, 2 showed a difference between
groups.103,120 One study showed a 30% increase of
volume compared to the control, ie, conventional fat
grafting.103 The other study showed a difference of 5%
less retention in the PRP group compared to the con-
trol group, in which PRF was used as a control.120 In 4
out of 9 PRP studies there was no difference between
groups.99,101,105,111 In the other 3 studies no statistical
tests were performed or could not be performed due to
the absence of controls.45,104,114
The 2 studies investigating supplementation of culture-
expanded ASCs both showed a dierence when com-
pared with the conventional fat graft.34,109 The volume
retention varied from 1.5-fold higher109 to 3-fold higher.34
Seven out of 9 studies with cSVF as supplement showed
a statistically significant increased volume compared with
the conventional fat graft (1.2- to 1.9-fold).97,103,104,106-108,119
Two studies showed no increased volume. One study
without a control group reported a retention of 68%.100 In 1
study no dierence between groups was found. Only 6 pa-
tients were included in that study and surgeons assessed
volume visually from 2D photographs.4
One study investigating tSVF supplementation showed
improved outcomes.112 A 2-fold increase in volume in
the supplemented group was found, but the measure-
ment methods on MRI were not described.112 The only
study describing PRP and cSVF mixed as a supplement
showed significantly increased volume retention (70%).103
However, the mix of PRP and cSVF did not result in addi-
tional volume increase compared with cSVF (73%) or PRP
(69%) alone.
Influence of Supplementation Therapies
on Patient Satisfaction
Patient satisfaction or patient-reported outcome
measures (PROMs) are considered the key out-
come measurement of facial aesthetic procedures.121
Validated and reliable outcome measures, eg, the
FACE-Q questionnaire, are readily available.122,123
Sixteen studies assessed patient satisfaction with the
FACE-Q, the Patient and Observer Assessment Scale
(POSAS), the Global Aesthetic Improvement Scale
(GAIS), a visual analog scale (VAS), the Likert scale,
or an NRS. The FACE-Q, GAIS, and POSAS are the
only validated outcome measures and were used in
4 studiesonly.
To evaluate the dierences in patient satisfaction be-
tween procedures in a controlled trial, the satisfaction
for both the intervention and the control group should
be evaluated and statistically tested for dierences. Nine
studies performed these “between-group” comparisons,
Author
(year)
Design Follow up
(months)
Indication Pathologya Injection
site
Total
(n)
Ageb
(years)
Female
(n)
BMI
(kg/m2)
Comorbidities Intervention
(fat +)
Intervention
(n)
Control Control
(n)
Minor
complications
Major
complica-
tions
Yoshimura et
al 2008
CCT 13 UP Parry-Romberg
and lupus
lipoatrophy
NR 6 42.5 [8.0]d4 NR NR cSVF 3 Fat 3 “All patients” Control
group: 33%
necrotized
tissue
requiring
surgical
removal
Where indicated, values are mean [standard deviation] or mean (range); NR, not reported; COPD, chronic obstructive pulmonary disease. Study design: RCT, ran-
domized controlled trial; CCT, controlled clinical trial; Cohort 2G, cohort study (2 groups, pre- + postoperative); Cohort 1G, cohort study (1 group pre- + postoperative);
Retrospective, retrospective study. Indication: UP, underlying pathology, meaning with underlying disease, trauma, or congenital volume loss; C, cosmetic, meaning
with no underlying pathology or facial disease, such as fat grafting for facial rejuvenation; C + FL, cosmetic with concomitant facelift. Enrichments, PRP, platelet-
rich plasma; PRF, platelet-rich fibrin; cSVF, cellular stromal vascular fraction; tSVF, tissue stromal vascular fraction; cASC, cultured adipose-derived stromal cell;
BMSC, bone marrow–derived stromal cell.aIn the cosmetic group, there is no pathology present (ie, facial rejuvenation).bWhen decimals are reported, these are
rounded to 1 decimal place.cSplit-face design: in the studies using a split-face design: the patients themselves serve as both intervention group (one half of the face)
and control group (the other half of the face).dWhen data are presented per group, the pooled value is calculated. —, not present in the study reported (eg, no control
group was present or no complications occurred in the study).
Table 1. Continued
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Table 2. Volume Outcomes
Author (year) Outcome
assessment
Follow up
(months)
Intervention
% retention
Control
% retention
Fold change Dierence in retentionb
(intervention compared with
control)
PRP/PRF
Bernardini
etal 2015
VA of volume 6 Good result (63%),
excellent result (37%)
Cervelli etal
2009
VA of volume 18 65% 26% 2.5
Fontdevila
etal 2014
CT 12 NR NR –0.3mL (−1.1 to –0.5mL)a (NS)
Gentile etal
2014
MRI 12 69% 39% 1.8 -
Keyhan etal
2013
Linear measurements
of photographs
12 82% (PRP) 87% (PRF) ND 5% ↑ (PRF) (P < 0.05)
Sasaki etal
2015
3D SI 12 69% [40%] 38% [13%] 1.8 31% ↑ (P < 0.01)
Sasaki etal
2019
3D SI 12 24% [10%] 21% [1%] 1.1 3% ↑ NS
Tenna etal US 12 0.7cm improvement 0.6cm improvement 1.1 0.1cm ↑ NS
Willemsen
etal 2018
VA of nasolabial fold 12 NR NR ND NS
ASCs
Bashir etal
2019
US 6 95% [4%] 31% [13%] 3.1 64% ↑ (P < 0.001)
Koh etal
2012
3D SI 6 79% 53% 1.5 26% ↑ (P = 0.002)
cSVF
Chang etal
2013
CT 6 68% [2%] 59% [1%] 1.2 10% ↑ (P < 0.001)
Gentile etal
2014
MRI 12 63% 39% 1.6 24% ↑ (P < 0.0001)
Lee etal
2012
NRS (1-10) 3 Malar eminence 7
(6-8)
Infraorbital region
7 (6-9)
Nasolabial fold 8
(7-9)c
Malar eminence 6 (5-7)
Infraorbital region 6 (5-6)
Nasolabial fold 6 (5-8)c
Malar 1.2
Infraorbital 1.2l
Nasolabial 1.3
Malar eminence 1↑ (P = 0.015)
Infraorbital region 1↑
(P = 0.010)
Nasolabial fold 2↑ (P = 0.017)
Li etal 2013 CT 6 65% [10%] 46% [9%] 1.4 18% ↑ (P < 0.01)
Sasaki etal
2015
3D SI 12 73% [50%] 38% [13%] 1.9 35% ↑ (P < 0.01)
Schendel
etal 2015
3D SI 12 68% ND
Tanikawa
etal 2013
CT 6 88% [13%] 54% [20%] 1.6 34% ↑ (P = 0.002)
Yin etal
2020
3D SI (handheld) 6 78% [12%] 56% [10%] 1.4 21% ↑ (P < 0.001)
Yoshimura
etal 2008
LS (1-4) 12 NR NR ND NS
8 Aesthetic Surgery Journal
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Schipper et al 9
but only 6 of these 9 studies performed statistical testing.
Patient satisfaction assessment was sometimes performed
together (or in the same room) with the operating sur-
geon,116 which may have induced interviewer bias and so-
cial desirability bias. Other studies omitted to describe the
conditions under which measurements were performed
and how results were obtained.102,104,112 Follow up was
sometimes not reported or ranged considerably within
studies (3-30months).109,112,113,118
Overall, patients reported high satisfaction rates after
both conventional and supplemented facial fat grafting.
Statistical tests were performed in 8 out of 16 stud
ies.98,101,102,110-112,117,119 Six of these 8 studies statistically
tested for dierences between the intervention and con-
trol group, of which 3 reported improved satisfaction in the
intervention group.101,102,110-112,117,119 Two PRP studies showed
no significant improvement, of which the study of Tenna
etal compared PRP with or without laser.101,111 One cSVF
study showed significant improvement and 1 cSVF showed
no significant improvement.110,119 Two tSVF studies showed
significant improvement.102,112
Complications
Minor complications occurred in 9 out of 27 studies. Three
out of these 9 studies also reported major complications
occurring in the acceptor site. Major complications were
reported in the groups supplemented with ASCs and PRP
and were also reported in the control groups (conventional
fat grafting). Overall, bruising and swelling were the most
common minor complications reported. Of the studies that
reported major complications Bernardini etal reported 3
cases of oily cysts that required surgical removal.114 Bashir
etal reported 2 cases of cellulitis: 1 in the intervention and
1 in the control group.34 Yoshimura etal reported a case of
necrotized tissue in the control group that was surgically
removed.4
DISCUSSION
Our study systematically reviewed the current literature
to assess the ecacy of supplemented clinical facial
fat grafting on volume retention. Our main results are
that: (1) few studies include volumetric data or patient
satisfaction; (2) these studies are heterogeneous with
respect to (a) age, (b) injection frequency, (c) injection
volume, (d) type of supplement, (e) mixing ratio of fat and
supplement, (f) imaging, (g) concomitant interventions,
(h) follow-up time, (i) outcome parameters, and (j) use
of controls; and therefore (3) the low number of studies
and their high heterogeneity did not allow for a proper
meta-analysis.
The results showed that of all supplements, culture-
derived ASCs were most effective at retaining injected
fat volume, whereas addition of PRP, or mixtures of PRP
and cSVF did not affect volume retention. Some of our
reviewed papers assessed complications and found
virtually none, irrespective of supplements. This cor-
roborates previous studies that show fat grafting to be
safe.2,124
A major shortcoming in virtually all analyzed papers is
the near lack of properly described standardized proced-
ures, and the reporting of interassay and intraassay vari-
ation. This causes several of the studies to be subjective
rather than objective and unfortunately reduces the value
of the outcomes.
Volume retention is the goal of facial fat grafting but is
also a highly challenging parameter to measure and mon-
itor. Several studies used validated imaging methods, in-
cluding CT and MRI scanning or 3D surface imaging. It was
Author (year) Outcome
assessment
Follow up
(months)
Intervention
% retention
Control
% retention
Fold change Dierence in retentionb
(intervention compared with
control)
tSVF
Gentile etal
2020
MRI 36 61% [5%] 31% [5%] 2 30% ↑ (P < 0.0001)
PRP + cSVF
Sasaki etal
2015
3D SI 12 70% [35%] 38% [13%] 1.8 31% ↑ (P < 0.01)
Where indicated, values are mean [standard deviation] or (range). —, no test was performed, or no quantification was described; NR, not reported; NS, not sig-
nificant. Outcome assessment: NRS, numeric rating scale; US, ultrasound; CT, computed tomography; LS, Likert scale; VA, visual assessment; SI, surface imaging.
Supplements: PRP, platelet-rich plasma; PRF, platelet-rich fibrin; cSVF, cellular stromal vascular fraction; tSVF, tissue stromal vascular fraction; ASC, adipose-derived
stromal cell; BMSC, bone marrow–derived stromal cell.aFontdevila etal described no separate intervention or control volume. Only a dierence between groups
with a range was described.bDierence is described in absolute percentage points; however, for the readibility of this table we have used the percentage sign
%.Dierences are based on the original (not rounded) data, which means rounding errors can be present.cLee etal described surgeon-rated volume consistency
based on a numeric rating scale.dGu etal described the thickness using the POSAS questionnaire. The specific question about thickness is extracted.
Table 2. Continued
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Table 3. Patient Satisfaction Outcomes
Author
(publication
year)
Outcome
assessment
Follow
up
(months)
Comparisonc Comparison with
preoperative
photographs
Satisfaction
intervention
Satisfaction
control
Dierence in satisfaction
(intervention compared with
control or postoperative
compared with preoperative)
PRP/PRF
Gennai etal
2017
LS (1-4) 6 Within-group
outcome
Yes Fair to good eect (2.6)
Gentile etal
2014
LS (1-6) 12 Within-group
outcome
Yes nr
Hesamirostami
etal 2019
GAIS 12 (6-30) Within-group
outcome
Yes Moderate to excellent
improvement, 7% poor
improvement.
Ozer etal
2019
FACE-Q 9 Within-group
change
Improved from
28.4 [23.3] to
90.3 [17.5]
61.9↑ (P < 0.001)
Tenna etal
2017
FACE-Q 6 Between-
group
outcome
No 84%b81%bNS
Willemsen
etal 2018
VAS (1-10) 6 Between-
group
outcome
No NR NR NS
ASCs/BMSCs
Bashir etal
2019
LS (1-5) 6 Between-
group
outcome
Yes 4.3 [0.7] 2.5 [0.5] 1.8↑ NSR
Jianhui etal LS (1-3) NR Between-
group
outcome
No NR NR
Koh etal 2012 VAS (1-5) NR Between-
group
outcome
No 4.5 3 .1 1.4↑ NSR
cSVF
Castro-Govea
etal 2018
LS of parents
(1-5)
18 Within-group
outcome
No 67% of the parents
were satisfied and 33%
were slightly satisfied
Lee etal 2012 NRS (1-10) 3 Between-
group
outcome
Yes Malar eminence 7 (6-8)
Infraorbital fold 8 (7-9)
Nasolabial fold 8 (7-9)a
Malar eminence
6 (5-8)
Infraorbital fold
6 (5-7)
Nasolabial fold 7
(5-8)a
Malar eminence 1↑ (P = 0.008)
Infraorbital fold 2↑ (P = 0.010)
Nasolabial fold 1↑ (P = 0.011)
Sterodimas
etal 2011
LS (1-5) 18 Between-
group
outcome
No 4.0 b4.0 b0 NS
Yin etal 2020 LS (1-5) 6 NR No
tSVF
Gentile etal
2020
LS (1-6) NR Between-
group
outcome
No 91% fully satisfied and
9% not fully satisfied
37% fully satis-
fied and 63% not
fully satisfied
(P = 0.031)
Gu etal 2018 POSAS 12 Within-group
change
Yes Preoperative 28.8 [1.0]
vs postoperative
12.2 [0.8]
16.6↓ (P < 0.001)d
10 Aesthetic Surgery Journal
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Schipper et al 11
surprising to note that none of the papers disclosed the
unbiased reliability, ie, inter- and intrameasurement varia-
tion, as well as inter- and intraobserver variation. This re-
duces the value of the measurements as these are prone
to subjectivebias.
With regard to the use of validated inquiries to
measure patient satisfaction and outcome, the FACE-Q,
GAIS, and POSAS have been available for several
years.121-123 Unfortunately, no more than a quarter of the
papers report utilizing these instruments. Again, com-
parisons with these instruments were not reported, but
we included these in our results. In general, statistical
testing of outcomes was neglected in more than half of
the studies. We consider this a major flaw that reduces
the value of potentially relevant clinical trials to a min-
imum. Journal editorial boards and peer-review pro-
cesses should continue to improve their standards for
statistics.
Our quest was to find published papers that reported
the benefit of supplemented fat grafting on volume re-
tention. However, we could neither corroborate nor
dispute these findings based on our current system-
atic literature analyses on supplemented clinical facial
fat grafting. This study focused on supplemented fat
grafting in the facial area, which might be a strength or
a limitation. Asystematic review on fat graft supplemen-
tation in other body parts would be interesting because
it may elucidate whether supplementation therapies
are effective and the influence of body location on fat
graft viability. One Russian study was excluded be-
cause no translation was available in the medical li-
brary. However, it is doubtful whether inclusion of this
study would have changed the general message of this
systematic review. Future studies should focus on con-
ducting well-designed randomized controlled clinical
trials to be able to establish a higher level of evidence
and to minimize inter- and intrastudy variation. Volume
outcome measurement should be performed with valid
imaging modalities and reliable volume measurement
methods. Inter- and intrameasurement variation should
be measured and reported. Imaging modalities based
on ionizing radiation, such as CT, for follow up should
be avoided. Validated patient-reported outcome ques-
tionnaires should be used and recorded both pre-
and postoperatively to minimize potential recall bias.
Procedures for harvesting and processing should be
standardized.12,125,126 No concomitant procedures such
as a facelift or blepharoplasty should be performed
during these studies because these influence volume
outcome and patient satisfaction. We have established
a summary of recommendations for the design of future
trials in Table 5.
CONCLUSIONS
Despite multiple studies showing improved volume re-
tention and increased patient satisfaction, no clinical su-
periority of supplementations could be objectified. Future
well-designed clinical trials may elucidate whether supple-
mentation therapies enhance fat graft retention and may
increase patient satisfaction.
Supplemental Material
This article contains supplemental material located online at
www.aestheticsurgeryjournal.com.
Acknowledgments
Drs Schipper and Vriend made an equal contribution to this
work as co-first authors.
Author
(publication
year)
Outcome
assessment
Follow
up
(months)
Comparisonc Comparison with
preoperative
photographs
Satisfaction
intervention
Satisfaction
control
Dierence in satisfaction
(intervention compared with
control or postoperative
compared with preoperative)
Wei etal 2017 nr 24 Between
group
outcome
No 90% 70% 20% ↑ (P < 0.01)
Where indicated, values are mean [standard deviation] or (range). NR, not reported; NS, not significant; NSR, no significance reported, no statistical test was per-
formed/reported; —, no quantification, no intervention or control group present or no statistical test reported. Outcome assessment: NRS, numeric rating scale, with
a higher number meaning a better score; LS, Likert scale, each number represents an outcome, such as unsatisfactory-slightly satisfactory, satisfactory; VAS, visual
analog scale; FACE-Q, a validated questionnaire using a combination of Likert scales and visual analog scales; POSAS, a validated questionnaire specifically de-
signed for scars (the overall patient-reported POSAS score is reported in this table; a lower score means a greater satisfaction); GAIS, Global Aesthetic Improvement
Scale is a Likert scale, 0-4. Supplements: PRP, platelet-rich plasma; PRF, platelet-rich fibrin; cSVF, cellular stromal vascular fraction; tSVF, tissue stromal vascular frac-
tion; ASC, adipose-derived stromal cell; BMSC, bone marrow–derived stromal cell.aOverall patient satisfaction was noted from the patient satisfaction scores.bData
were manually calculated from the tables in the article.cWithin-group outcome means that no comparison to baseline or comparison to a control group was made.
Participants were asked to evaluate the outcome after surgery without evaluating the preoperative situation.dA lower score of the POSAS questionnaire means a
greater satisfaction.
Table 3. Continued
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Disclosures
The authors declared no potential conflicts of interest with re-
spect to the research, authorship, and publication of this article.
Funding
This study was funded by the Departments of Oral and
Maxillofacial Surgery, Plastic and Reconstructive Surgery, and
Table 4. Quality of the Included Studies Based on the Eective Public Health Practice Project Tool
Reference Selection bias Study Design Confounders Blinding Data Collection Dropouts Global rating
Bashir etal 2019 0 0 0 +
Bernardini etal 2015 0 0
Castro-Govea etal 2018 0 0
Cervelli etal 2009 0
Chang etal 2013 + 0
Fontdevila etal 2014 0 + + + + 0
Gennai etal 2017 0 NA
Gentile etal 2014 0 + 0 0
Gentile etal 2020 0 0
Gu etal 2018 0 +
Hesamirostami etal 2019 0 0 + +
Jianhui etal 2014 0
Keyhan etal 2013 + + 0
Koh etal 2012 + + 0 +
Lee etal 2012 0 + 0
Li etal 2013 0 + 0 0 NA 0
Ozer etal 2019 0 + 0 + NA 0
Sasaki etal 2015 0 0
Sasaki etal 2019 + + 0 0
Schendel etal 2015 0 + 0 0 + 0
Sterodimas etal 2011 + 0 0
Tanikawa etal 2013 0 + + 0 0 0 +
Tenna etal 2017 + 0 +
Wei etal 2017 + 0
Willemsen etal 2018 + + 0 + 0 0
Yin etal 2020 + + + 0 + 0
Yoshimura etal 2008 + + 0
Totals
Weak, n (%) 23 (85%) 0 (0%) 13 (48%) 7 (26%) 12 (44%) 18 (67%) 20 (74%)
Moderate, n (%) 4 (15%) 15 (56%) 1 (4%) 18 (67%) 8 (30%) 2 (7%) 6 (22%)
Strong, n (%) 0 (0%) 12 (44%) 13 (48%) 2 (7%) 7 (26%) 4 (15%) 1 (4%)
The totals at the bottom represent the distribution of how weak, moderate and strong each criterion is. Ref, reference, +, strong, 0, moderate, –, weak.
12 Aesthetic Surgery Journal
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Schipper et al 13
Pathology and Medical Biology, University and Medical Center
Groningen, Groningen, the Netherlands.
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Table 5. Recommendations for the Study Design of New Trials
Recommendations
for new studies
Quality of the study 1. Controlled design (comparison with standard treatment or placebo)
2. Randomized
3. Minimal follow-up duration of 12months
4. Following CONSORTa statement for reporting
5. Statistically testing for dierences between groups
Standardization of
the procedure
1. Standardized harvesting, processing and injection technique
2. Standardized injection volume and volume-to-volume ratio of supplement-to-fat graft
3. No concomitant procedures (eg, facelift) that can influence volume or satisfaction outcomes
4. Single injections, no repeated procedures
Measurement of
volume retention
1. Clear definition of how retention is measured, based on injected volume or based on first volume measurement after surgery
2. Using valid imaging modalities (without ionizing radiation)
3. Using a reliable method of volume measurement, by either reporting reliability or using a validated method of volume measure-
ment
Measurement of pa-
tient satisfaction
1. Using a validated PROMb
2. Measuring change of PROM, including a preoperative (baseline) measurement
3. Statistically testing for dierence of PROM between intervention and control group
4. Observer/surgeon should not be present when PROM is recorded, to exclude interviewer/social desirability bias
aConsolidated Standards of Reporting Trials.bPatient-reported outcome measures.
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... The addition of autologous components is also a direction of great interest in the scientific community to improve fat graft viability. Previous studies on the improvement of fat graft viability by supplementing exogenous components include the addition of platelet-rich plasma (PRP), plateletrich fibrin (PRF), enzymatic digested adipose stem cells (ASCs), bone marrow-derived stromal cells (BM-MSCs), and cellular or tissue stromal vascular fraction (cSVF, tSVF) [23,27,28]. PRP and PRF are blood derivatives, and their capacity to effectively enhance volume retention is controversial [29,30]. ...
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Oil compromises graft outcomes via inflammation, which accounts for the unpredictability of volume retention rates as low as 20%. Existing techniques for oil removal are relatively inefficient. In this study, a novel approach was taken to prepare concentrated deoiled fat (CDF) by utilizing flocculation and centrifugation to remove the oil. The hypothesis put forward in this study was that CDF would exhibit improved volume retention and quality by enhancing purification efficiency and reducing inflammation. This basic research involved both in vitro and in vivo experiments using samples obtained from women who underwent abdominal liposuction. The CDF was prepared by flocculation and centrifugation. In the vitro experiments, the microstructure of fat was assessed using Calcein acetoxymethyl ester (AM) staining for living cells and propidium iodide (PI) staining for dead nuclei in two groups: Coleman fat group and CDF group. Additionally, the glucose uptake capacity of these two groups was evaluated using the glucose transport test (GTT). In the vivo experiments, the study included three groups: two experimental groups (low-volume concentrated deoiled fat, LCDF; high-volume concentrated deoiled fat, HCDF) and one control group (Coleman fat), with 10 healthy female BALB/c nude mice in each group, 1ml of the graft was injected subcutaneously to each mouse. After 8 weeks, the fat grafts were harvested and subjected to volume evaluation, HE staining and immunostaining for perilipin to assess graft outcomes. In the vitro experiments, the concentration rate of the CDF was found to be 79.6% that of Coleman fat, with 15.1% more oil separated. Cell viability, as assessed by AM/PI staining, did not show a significant difference between the two grafts, but the results of the GTT showed that the tissue viability of the CDF was higher than that of Coleman fat. In the vivo experiments, the CDF had higher volume retention than Coleman fat, as measured by water displacement. Histopathologic scoring indicated that HCDF group and LCDF group had a more intact fat structure with fewer vacuoles, inflammation, and fibrosis compared to Coleman fat. Additionally, the percentages of perilipin-positive area in the LCDF group and HCDF group were higher than in the Coleman group, indicating improved graft quality and outcome with the use of concentrated deoiled fat. “Concentrated deoiled fat” refers to an autologous fat graft from which oil has been removed by flocculation and centrifugation. This process increases volume retention and viable cells and decreases infiltrated inflammatory cells. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.
... Therapeutic management should include interdisciplinary care, which should include treatment aimed at stopping the disease process, but also procedures aimed at restoring the resulting defects [43,[65][66][67][68][69][70]. The need to conduct randomized clinical trials, verify the effectiveness of selected treatment methods, systematize and standardize diagnostic and treatment guidelines as well as measurement methods, enabling an objective assessment of tissue volume in places affected by the disease, the need to establish standards for the time that should elapse from remission to starting augmentation therapy [71]. ...
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Morphea en coup de sabre and progressive hemifacial atrophy are extremely rare connective tissue disorders causing facial deformity. In extreme cases, morphological disorders are accompanied by symptoms of a clear impairment of the stomatognathic system. The aetiology of the above-mentioned diseases is still unknown. Properly planned therapy in the field of maxillofacial orthopaedics makes it possible to correct the asymmetric pattern of hard tissue growth and thus enable rehabilitation. The task of augmentation techniques is the volumetric supplementation of tissue defects resulting from atrophic processes. The degree of destruction and the extent of changes determine the method of correction. Mild and moderate defects are treated mainly with biomaterials and autologous adipose tissue. The severe course of hemifacial atrophy and morphea en coup de sabre and the associated significant tissue atrophy necessitate the search for more complex methods of treatment. In this paper, we summarize the disturbances of the stomatognathic system in patients with craniofacial morphea, together with an analysis of current treatment options.
... There are three main purposes of facial fat grafting: volume restoration (filling to the deep layer, providing tissue support, and improving facial contours), fine contouring (filling to the superficial layer, providing limited volumization, and modest regeneration), and tissue repair (intradermal filling, predominantly used to fix aged, and damaged tissue). According to the previous reports of the applicability of various fat products, 14 here, we suggested our pyramidal multipletheory (PMT) fat grafting strategy. The fundamental aspect of this strategy was deep layer filling which provided restoration of volume along with a prominent supportive effect. ...
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Background: Age-related changes to the face pertinent anatomy and important aspects of autologous fat grafting have been widely applied in facial rejuvenation. Various types of autologous fat products (Macrofat, Microfat, SEFF, nanofat, and SVF-gel) with different properties and applicabilities have been introduced and available for surgeons. Methods: Key differences between common techniques for fat processing and infiltration. Develop a plan for patients based on site-specific facial anatomical zones, we suggested a pyramidal multiple-theory (multi-type, multi-method and multi-layer) for facial fat grafting. Based on the complicated mechanism of the face decrepitude in different layers of facial soft tissue, autologous fat products with various particle sizes and components into different layers. Results: Fifty-eight patients underwent this facial fat grafting strategy from June 2020 to Jan 2022. All achieved cosmetic improvements, with higher patients' satisfaction, and minor complications. Our facial fat grafting strategy takes advantage of different fat products and is able to address the physiological tissue changes during aging, more properly and targetedly, than the traditional facial fat grafting. Conclusions: Fat grafting to the face aids in volume restoration and rejuvenation, thereby addressing soft-tissue atrophy associated with the aging face, acquired conditions, or congenital malformations. The technique described as "lipo-tumescence" has been successfully used in the breast and other regions of the body that have radiation damage and is discussed in this article specifically for the face and neck.
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The obesity pandemic increasingly causes morbidity and mortality from type 2 diabetes, cardiovascular diseases and many other chronic diseases. Fat cell size (FCS) predicts numerous obesity-related complications such as lipid dysmetabolism, ectopic fat accumulation, insulin resistance, and cardiovascular disorders. Nevertheless, the scarcity of systematic literature reviews on this subject is compounded by the use of different methods by which FCS measurements are determined and reported. In this paper, we provide a systematic review of the current literature on the relationship between adipocyte hypertrophy and obesity-related glucose and lipid dysmetabolism, ectopic fat accumulation, and cardiovascular disorders. We also review the numerous mechanistic origins of adipocyte hypertrophy and its relationship with metabolic dysregulation, including changes in adipogenesis, cell senescence, collagen deposition, systemic inflammation, adipokine secretion, and energy balance. To quantify the effect of different FCS measurement methods, we performed statistical analyses across published data while controlling for body mass index, age, and sex.
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We read with interest Yu et al's preclinical study on the effect of platelet-rich fibrin (PRF) on fat-grafting volume and viability in nude mice. The poor survival of adipocytes and adipose-derived stem cells within fat grafts hinders the use of fat grafting in all clinical settings. We commend the authors on their methodologically robust study design, which was well powered (n = 120), included randomization, and used appropriate histologic stains for adipocyte viability among others. The authors discuss how PRF may be a superior adjunct for increasing fat graft survival than other autologous sources of growth factors (eg platelet-rich plasma [PRP]). This is based on the finding that PRF releases proangiogenic growth factors over a longer time period (14-20 days). We disagree that this is preferable. It has been well established by Eto et al that, in mice, adipocytes located more than 300 μm from the periphery of the fat graft become nonviable in just 24 hours. Therefore any adjunct must act very rapidly, and our opinion is that a prolonged delivery of growth factors after this 24-hour window will do nothing for nonviable adipocytes. Theory aside, it would be interesting to see PRF and PRP compared directly in a similar animal study, to determine if one has a superior effect on fat graft survival/viability. To date there has only been 1 study comparing PRF and PRP directly, and this found no difference; however, that study was insufficiently powered (n = 20) to identify small differences.
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Background Fat graft enhanced with adipose-derived stromal vascular fraction cells (FG-SVFs) has been used in regenerative plastic surgery, for aesthetic and reconstructive purposes. The authors present their experience using FG-SVFs obtained by minimal manipulation, in face rejuvenation. Objectives The aim of this study was to evaluate the safety and efficacy of the use of FG-SVFs in face rejuvenation for aesthetic improvement, comparing the results with a control group treated with the Fat graft not enhanced with adipose-derived stromal vascular fraction cells (FG) according to Coleman technique. Methods 33 female patients (ages ranged between 19 and 68 years) affected by face’s soft-tissue defects with loss of volume and elasticity and signs of aging were treated with FG-SVFs, comparing results with a control group (n=30) treated with not enhanced fat graft (FG). The pre-operative analysis included a complete clinical evaluation, a photographic assessment, magnetic resonance imaging (MRI) of the soft tissue and ultrasound (US). Post-operative follow-up was performed at 1, 3, 7, 12, 24, 48, weeks and then annually. Results The patients treated with FG-SVFs showed 61% maintenance of the contour restoring and of three-dimensional volume after 3 years compared with the patients of the control group treated with FG, who showed 31% maintenance. 60.7% (n=20) of patients treated with FG-SVFs, was observed a restoration of the face contour and an increase of 6.6 mm in the three-dimensional volume after 36 months, which was reported in only 33,3% (n=10) of patients in the control group treated with FG. Volumetric persistence in the study group was higher than that in the control group (p <. 0001 vs. control group). MRI and US moreover confirmed the absence of important side effects, as fat necrosis, and cytosteatonecrotic areas. Conclusions The use of FG-SVFs was safe and effective in this series of case treated.
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Background: Stem cells from adipose tissue (ADSCs) and platelet-rich plasma (PRP) are innovative modalities that arise due to their regenerative potential. Objective: The aim of this study was to characterize possible histological changes induced by PRP and ADSC therapies in photoaged skin. Methods: A prospective randomized study involving 20 healthy individuals, showing skin aging. They underwent two therapeutic protocols (protocol 1: PRP; protocol 2: ADSCs). Biopsies were obtained before and after treatment (4 months). Results: PRP protocol showed unwanted changes in the reticular dermis, mainly due to the deposition of a horizontal layer of collagen (fibrosis) and elastic fibers tightly linked. Structural analyses revealed infiltration of mononuclear cells and depot of fibrotic material in the reticular dermis. The ADSC protocol leads to neoelastogenesis with increase of tropoelastin and fibrillin. There was an improvement of solar elastosis inducing an increment of macrophage polarization and matrix proteinases. These last effects are probably related to the increase of elastinolysis and the remodeling of the dermis. Conclusions: The PRP promoted an inflammatory process with an increase of reticular dermis thickness with a fibrotic aspect. On the other hand, ADSC therapy is a promising modality with an important antiaging effect on photoaged human skin.
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Background: Autologous fat grafting is a dynamic modality used in plastic surgery as an adjunct to improve functional and aesthetic form. However, current practices in fat grafting for soft-tissue augmentation are plagued by tremendous variability in long-term graft retention, resulting in suboptimal outcomes and repetitive procedures. This systematic review identifies and critically appraises the evidence for various enrichment strategies that can be used to augment and improve the viability of fat grafts. Methods: A comprehensive literature search of the Medline and PubMed databases was conducted for animal and human studies published through October of 2017 with multiple search terms related to adipose graft enrichment agents encompassing growth factors, platelet-rich plasma, adipose-derived and bone marrow stem cells, gene therapy, tissue engineering, and other strategies. Data on level of evidence, techniques, complications, and outcomes were collected. Results: A total of 1382 articles were identified, of which 147 met inclusion criteria. The majority of enrichment strategies demonstrated positive benefit for fat graft survival, particularly with growth factors and adipose-derived stem cell enrichment. Platelet-rich plasma and adipose-derived stem cells had the strongest evidence to support efficacy in human studies and may demonstrate a dose-dependent effect. Conclusions: Improved understanding of enrichment strategies contributing to fat graft survival can help to optimize safety and outcomes. Controlled clinical studies are lacking, and future studies should examine factors influencing graft survival through controlled clinical trials in order to establish safety and to obtain consistent outcomes.
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Background Cell-assisted lipotransfer (CAL) promotes the survival of fat grafts with high vascular density and improves skin qualities by increasing collagen content. However, no study has quantified the changes on the skin surface, and rigorous methodological evaluations are still lacking. Design Fifty patients were recruited and randomly divided into two groups: experimental group (n=25) who were given SVF-assisted fat graft and control group (n=25) who underwent fat graft only. Methods The SVF cells were counted, tested in terms of viability, and characterized. The volumes of whole faces were determined by using a 3D scanner and Geomagic software preoperatively, immediately after surgery, and 6 months postoperatively. Facial skin qualities, including spots, wrinkles, texture, pores, UV spots, brown spots, red areas, and porphyrins, were detected by a VISIA skin detector preoperatively and 6 months postoperatively. A visual analog scale was used for clinical evaluation. Results The cell pellet contained 1–3 × 10⁷/mL of fresh SVF cells. The cell viability exceeded 98%. The immunophenotyping characteristics and stemness were consistent with the features of adipose-derived stem cells (ADSCs). The survival rate of SVF-enriched fat grafts was significantly higher than that of control grafts: 77.6%±11.6% versus 56.2%±9.5% (p<0.001). The VISIA values of wrinkles (19.3±6.6 versus 10.9±5.5, p<0.001) and texture (15.8±7.0 versus 10.3±5.0, p<0.01) were significantly higher in SVF-enriched group than in control group at 6 months postoperation. During long-term follow-up, the majority of patients in both groups were satisfied with the final face aesthetic results. Conclusions Our results demonstrated the positive outcomes of autologous SVF-assisted fat graft in improving facial skin quality and its promising application potential in clinical settings. This study is registered at www. ClinicalTrials.gov, number NCT02923219.
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Quick absorption of adipose tissue grafts makes the outcomes less satisfactory for clinical applications. In the current study, adipose tissue grafts were mixed with adipose tissue-derived stem cells (ASCs) to improve retention of adipose tissue grafts and to make the clinical outcomes of fat grafting more reliable. Adipose tissue was either injected alone (conventional group) or mixed with ASCs (stem cell group) before injection. In both groups, adipose tissue was injected at the site of contour throughout layers of tissues till visual clinical symmetry with the opposite side was achieved. The volume of injected fat graft was measured after 72 hours and 6 months using a B-mode ultrasound device connected with a 12 MH frequency probe. The percentage reduction in the volume of injected fat, physician satisfaction scores (Ph-SCs), and patient satisfaction scores (P-SCs) were also recorded. After 6 months, there was significantly lower fat absorption in the stem cell group as compared to the conventional group. Mean physician and patient satisfaction scores were significantly improved in the stem cell group. No significant adverse effects were noted in any patient. Significantly lower absorption of graft due to the use of ASCs improves the clinical outcomes of conventional fat grafting for contour deformities of the face. The current preenrichment strategy is noninvasive, safe and can be applied to other diseases that require major tissue augmentation such as breast surgery. This trial is registered with NCT02494752 .
Article
Background: Autologous fat grafting is common in facial reconstructive and cosmetic surgeries; the most important drawbacks are the high absorption rate and unpredictable volume retention rate. Surgeons usually make clinical judgements based on their own experience. Therefore, this study aimed to systematically and quantitatively review the volume retention rate of facial autologous fat grafting and analyse the relevant influencing factors. Methods: A systematic literature review was performed using the Medline, EMBASE, Cochrane Library, and Web of Science databases in October 2019 for articles that reported objectively measured volume retention rates of facial fat grafting. Patient characteristics, fat graft volumetric data, and complications were collected. A meta-analysis using a random-effects model was conducted to pool the estimated fat retention rate. Relevant factors were analysed and reviewed on the basis of subgroups. Results: We included 27 studies involving 1011 patients with facial fat grafting. The volume retention rate varied from 26 to 83%, with a mean follow-up of 3-24 months. The overall pooled retention rate was 47% (95% CI 41-53%). The volume measurement method significantly influenced the reported retention rate. A trend towards better retention was found for secondary fat grafting procedures and patients with congenital deformities. Only 2.8% of all patients had complications. Conclusion: The exact percentage of facial fat grafts retained is currently unpredictable; the reported rate varies with different estimation methods. This review analysed studies that provided objectively measured volume retention rates, the pooled average percentage of facial fat graft retention (47%, 95% CI 41-53%), and relevant factors. Level of evidence iii: This journal requires that authors assign a level of evidence to each article. For a full description of these evidence-based medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.
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This study used stromal vascular fraction gel (SVF-gel), a mechanically processed fat-derived product, to treat eye bag and tear trough deformity. SVF-gel is prepared by a process of centrifugation and intersyringe shifting and is particularly rich in SVF cells and native adipose extracellular matrix. SVF-gel injection is used alone or combined with transconjunctival eye bag removal. High satisfaction was noted among patients treated with SVF-gel injection for periorbital rejuvenation with fairly low complication rates. SVF-gel injection is a good alternative to assist transconjunctival lower eyelid blepharoplasty and correct the palpebromalar groove, tear trough deformity, and supraorbital hollow.
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Reversing structural changes in aging skin gained potential after the therapeutic use of adipose-derived stem cells was described. Nanofat is a highly concentrated solution of progenitor cells without viable adipocytes. Nanofat grafting creates striking skin quality improvement. The availability of adipose-tissue combined with straightforward mechanical protocol to process fat brings regenerative and antiaging medicine into real-life clinical practice. Association with other cofactors (hyaluronic acid, botulin toxin, and vitamin C) and therapies (microneedling and drug delivery) provides better outcomes. This article describes the techniques and the authors' experiences in nanofat grafting, and its potential new applications in regenerative medicine.