Archives of Dermatological Research

https://doi.org/10.1007/s00403-019-01999-6

REVIEW

A systematic review of the safety and effectiveness of platelet‑rich

plasma (PRP) for skin aging
Amanda L. Maisel‑Campbell1 · Aliaa Ismail1,2 · Kelly A. Reynolds1 · Emily Poon1 · Linda Serrano1,6 ·
Solomiya Grushchak1,3 · Carmen Farid2 · Dennis P. West1 · Murad Alam1,4,5

Received: 14 August 2019 / Revised: 23 September 2019 / Accepted: 3 October 2019

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Abstract
Injection of platelet concentrates for the treatment of aging skin has gained popularity. The objective was to systematically
assess the evidence regarding the safety and effectiveness of platelet-rich plasma (PRP) for reducing the visible signs of aging.
Cochrane Library, MEDLINE (PubMed), EMBASE, and Scopus were searched from inception to March 2019 for prospec-
tive trials and case series assessing PRP for skin aging in 10 or more patients. Twenty-four studies, including 8 randomized
controlled trials (RCTs), representing 480 total patients receiving PRP, were included. Based on physician global assessment,
injection PRP monotherapy was shown to at least temporarily induce modest improvement in facial skin appearance, texture,
and lines. Periorbital fine lines and pigmentation may also benefit. Adjuvant PRP accelerated healing after fractional laser
resurfacing. Although the degree of improvement was typically less than 50%, patients generally reported high satisfaction.
It was limited by heterogeneity in PRP preparation and administration, and lack of standardization in outcome measures.
PRP injections are safe and may be modestly beneficial for aging skin. The evidence is most convincing for improvement
of facial skin texture. The persistence of these effects is not known. More high-quality trials with sufficient follow-up are
needed to optimize treatment regimens.

Keywords Platelet-rich plasma · PRP · Aging · Photoaging · Rejuvenation · Systematic review · Safety · Effectiveness

Introduction

Platelet-rich plasma (PRP) is an autologous solution con-

taining supraphysiologic concentrations of platelets (greater
Amanda L. Maisel-Campbell and Aliaa Ismail contributed equally than 1 × 106/µL) in plasma. PRP includes over 800 bioactive
to this work and are the co-first authors. molecules [1, 2] such as mitogenic and chemotactic growth
factors released from the alpha granules of activated plate-
* Murad Alam
m‑alam@northwestern.edu lets: platelet-derived growth factors (PDGF), transforming
growth factor-β1 (TGF-β1), TGF-β2, vascular endothelial
1
Department of Dermatology, Feinberg School of Medicine, growth factor (VEGF), basic fibroblast growth factor (bFGF)
Northwestern University, 676 N. St. Clair St., Ste 1600, and epithelial growth factor (EGF). These constituents may
Chicago, IL 60611, USA
impact tissue repair and other cellular events through the
2
Department of Dermatology, Venereology and Andrology, upregulation of genes responsible for cellular proliferation
Alexandria University, Alexandria, Egypt
and differentiation, angiogenesis, and extracellular matrix
3
Division of Dermatology, Stritch School of Medicine, Loyola synthesis [3–5].
University, Chicago, IL, USA
Platelet concentrates have been used for tissue regenera-
4
Department of Otolaryngology, Feinberg School tion [6–9]. PRP injection for treatment of aging skin has also
of Medicine, Northwestern University, Chicago, IL, USA
gained popularity. This review assesses the evidence for the
5
Department of Surgery, Feinberg School of Medicine, safety and effectiveness of PRP for treatment of the visible
Northwestern University, Chicago, IL, USA
signs of skin aging.
6
Department of Dermatology, Medical College of Wisconsin,
Milwaukee, WI, USA

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Methods
Cochrane Library, MEDLINE (PubMed), EMBASE and
Scopus were searched from inception through March 15,
2019 for English language clinical trials of PRP for skin
aging. Search terms were [platelet rich plasma AND
(aging, photodamage, photoaging, wrinkles, photoaging,
OR rejuvenation)].
Included studies: (1) were randomized or other controlled
trials, prospective cohort studies, or case series (CS); (2)
had ≥ 10 subjects, who were; (3) ≥ 18 years old; and (4)
measured the effect of PRP on skin aging. Combination
treatments was included if the effect of PRP was reported
separately. Excluded were: (1) in vitro studies; (2) animal
studies; (3) ‘grey literature’ (conference abstracts, unpub-
lished studies); (4) letters; and (5) reviews.
Screening of titles, abstracts, and full-text articles was
performed independently by two reviewers (AI and AM).
For articles meeting inclusion criteria, two raters (KR and
MA) independently ranked the quality of evidence using a
modified Oxford Centre for Evidence-Based Medicine hier-
archy: (1a) systematic review of RCTs; (1b) individual RCT;
(1c) all or none study; (2a) systematic review of cohort stud-
ies; (2b) individual cohort study; (2c) outcomes research;
Fig. 1  PRISMA flow chart of
identification of eligible studies
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Archives of Dermatological Research
(3a) systematic review of case–control studies; (3b) indi-
vidual case–control study; (4) case series; and (5) expert
opinion. Disagreements were resolved with discussion and
forced agreement.
The same reviewers independently extracted, if present:
first author; publication year; country; study design; patient
number; age; sex; skin phototype; method of PRP prepa-
ration, treatment regimen; session number; study duration;
follow-up duration; reported outcomes; and reported side
effects. Follow-up was classified as short (< 1 month),
medium (1–6 months), or long (≥ 6 months). Results
from ordinal global improvement scales were converted
to a standardized scale (no improvement, < 25%, 25–50%,
50–75%, and 75–100%).
Results
The initial 1407 articles were reduced to 24 studies (Fig. 1): 9
RCTs; [10–16, 28, 32] 2 prospective comparative cohort stud-
ies; [3, 17] and 13 CS [18–27, 29–31] (Tables 1, 2, 3). RCTs
included 179 subjects, prospective comparative cohort studies
100, and CS studies 252. Of 531 total subjects, 480 received
 Table 1  PRP method of preparation, treatment details, and duration of follow-up of included studies
References No. of Treatment Volume of PRP volume Mean platelet concentration (min– Method of PRP prepara- % Platelet Mean WBCs Anti-coag- Activatora Follow-upb
treat- interval blood drawn max) tion yield (min–max) ulant
ments
Blood PRP

Kim and 1 – NR 1 mL NR NR Single-spin NR NR NR No > 2 weeksc

Gallo [14] (3100 rpm × 9 min)
Na [15] 1 – 10 mL 2.5 mL NR NR Double-spin (1st: NR NR ACD CaCl2 4 weeks
160 g × 10 min, 2nd:
400 g × 10 min)
Shin [16] 3 4 weeks 12 mL 3 mL NR NR Double-spin (1st and 2nd: NR NR CPD-A CaCl2 4 weeks
Archives of Dermatological Research

3000 rpm × 5 min)

Hui [12] 3 12 weeks 30 mL 2.2 mLd NR NR (700 × 109/L Double-spin (1st: NR NR Heparin CaG 12 weeks
to 1000 × 109/L) 1200 rpm × 10 min, calcium
2nd: 3500 rpm × 5 min)
Alam [10] 1 – 20 mL 3 mL NR NR SmartPREP® 2 NR NR ACD No 24 weeks
APC + (Harvest Tech-
nologies)
Gawdat [11] 6 2 weeks 10 mL 3 mL NR NR Double-spin (1st: NR NR ACD CaCl2 12 weeks
150 g × 15 min, 2nd:
400 g × 15 min)
Kang [13] 3 4 weeks 12 mL 1 mL NR Respondersc MyCells® Kit (Estar NR NR ACD No 12 weeks
812.5 × 109/L Technologies Ltd)
(NR)
Partial
­respondersd
815.7 × 109/L
(NR)
Non-responders
d
799.5 × 109/L
(NR)
Sevilla [17] 1 – 34 mL 2.5 mL NR 625 × 109/Le Double-spin (1st: NR NR ACD No 52 weeks
150 g × 15 min, 2nd:
2700 g × 10 min)
Abuaf [3] 1 – 8 mL 2 mL NR NR RegenLab® Kit (Regen NR NR Sodium CaCl2 4 weeks
Lab) citrate
Cameli [19] 3 4 weeks 9 mL 4 mLf NR 1680 × 109/L Cascade System Kit 82 (47–100) 1.9 cells/L Sodium No 4 weeks
(885– (0–7.6) citrate
3760 × 109/L)
Elnehrawy 1 – 8 mL 4 mLf NR NR Double-spin buffy coat NR NR Sodium CaCl2 8 weeks
[21] (1st: 388 g × 7 min, citrate
2nd: 1376 g × 5 min)
Cabrera- 3 4 weeks NR 1.5 mL NR NR Double-spin NR NR Sodium CaG 4 weeks
Ramirez buffy coat (1st: citrate
[18] 1500 rpm × 10 min,
2nd
2000 rpm × 10 min)
Sclafani 1 – 9 mL 1–2.5 mL per NR NR Selphyl kit, Aesthetic NR NR NR CaCl2 12 weeks
[25] NLF Factors

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 Table 1  (continued)
References No. of Treatment Volume of PRP volume Mean platelet concentration (min– Method of PRP prepara- % Platelet Mean WBCs Anti-coag- Activatora Follow-upb
treat- interval blood drawn max) tion yield (min–max) ulant

13
ments
Blood PRP

Scarano 3 4 weeks 3.6 mL 0.2 mL NR NR Single-spin NR NR Sodium No 24 weeks

[24] (1100 rpm × 4 min) citrate
Díaz-Ley 3 3 weeks 36 mL NR NR NR PRGF BTI Kit NR NR Sodium PRGF acti- 6 weeks
[20] citrate vator
Mehryan [22] 1 – 10 mL 1.5 mLg NR NR PRP Kit (KimiaTeb NR NR ACD CaCl2 12 weeks
Rahavard Co.)
Redaelli [23] 3 4 weeks 16 mL 4 mLh NR NR RegenLab® Kit (Regen NR NR NR CaCl2 4 weeks
Lab)
Abdul-Hus- 3 4 weeks 13.5 mL 3 mL NR NR Ycellbio-kit NR NR Sodium CaCl2 12 weeks
sein [26] citrate
Charles-de- 1 – NR NR NR NR Double-spin (1st: NR NR Sodium CaCl2, 12 weeks
Sa [27] 300 g × 5 min, 2nd: citrate thrombin
700 g × 17 min)
El-Domyati 6 2 weeks 10 mL NR NR NR Double-spin (1st: NR NR ACD CaG 2 weeks
[28] 252 g × 10 min, 2nd:
1792 g × 5 min)
Everts [29] 3 4 weeks 50 mL 7 mL NR NR EmCyte ­PurePRP® NR NR Sodium CaCl2 12 weeks
citrate
Fedyakova 3 4 weeks NR 2–4 mL 212 × 109/L (NR) 524 × 109/L (NR) PRGF BTI Kit NR NR Sodium PRGF acti- 4 weeks
[30] citrate vator
Lee [31] 1 – 8 mL 4 mLi NR NR Single-spin buffy coat NR NR EDTA No 6 weeks
(3200 rpm × 5 min)
Willemsen 1 – 30 mL 3 mLj 243 × 109/L NR Biomet GPSIII device NR NR ACD NR 52 weeks
[32] (153–
312 × 109/L)

PRP platelet-rich plasma, WBCs white blood cells, NR not reported, ACD acid citrate dextrose, CPD citrate–phosphate–dextrose–adenine, CaCl2 calcium chloride, CaG calcium gluconate, NLF
nasolabial fold, PRGF platelet-rich growth factor
a
Exogenous activation, ‘no’ indicates endogenous activation
b
Indicates after final study treatment
c
Follow-up visits occurred every 2–3 days until re-epithelialization and for several days after until all cases of erythema had resolved
d
’Responders’ were defined as having achieved > 25% improvement in wrinkles or skin tone, ‘partial responders’ achieved < 25% improvement and ‘non-responders’ had no interval change
after treatment in wrinkles and skin tone
e
0.9 mL into cheeks, 0.6 mL into perioptic corium layer, and 0.7 mL into the forehead
f
1 mL into each cheek, 1 mL into NLFs, 1 mL into crow’s feet and forehead
g
1 mL into infraorbital region, 0.5 mL into crow’s feet
h
1 mL into forehead and crow’s feet, 1 mL into cheeks, 1 mL into NLFs and marionette lines, 1 mL into neck
i
2 mL into each cheek, divided among six injection points on each side
j
Injected in lipofilling planes in the midface and temporal regions
Archives of Dermatological Research
Archives of Dermatological Research

Table 2  Characteristics of the included studies

Source Country Study design Area treated Quality Intervention No. of sub- Age, mean Sex (F) Fitzpat-
­ratinga jects (min–max), rick skin
year type

PRP in combination with laser resurfacing

Kim and USA Double-blind Forearm 1b 1: Frac. ­CO2 15 “≥ 18”b NR I–V
Gallo [14] split-body laser + ID
RCT​ PRP
2: Frac. ­CO2
laser + saline
Na [15] Korea Split-body Inner arm 1b 1: Frac. ­CO2 25 NRb NR NR
RCT​ laser + ID
PRP
2: Frac. ­CO2
laser + saline
Shin [16] Korea Single-blind Full face 1b 1: Frac. 1: 11 1: 44 (30–56) 22 IV–V
RCT​ Er:Glass 2: 11 2: 44 (38–50)
laser + topical
PRP
2: Frac.
Er:Glass laser
Hui [12] China Single-blind Full face 1b 1: Frac. ­CO2 13 42 (32–57) 13 III–IV
split-face laser + ID
RCT​ PRP
2: Frac. ­CO2
laser + saline
PRP in combination with lipofilling
Willemsen Netherlands Double-blind Full face 1b 1: Lipofill- 1: 13 52 (38–63) 1: 13 2: 12 –
[32] RCT​ ing + ID PRP 2: 12
2: Lipofill-
ing + saline
PRP monotherapy
Alam [10] USA Double-blind Cheeks 1b 1: ID PRP 19 46 (18–70) 17 NR
split-face 2: ID saline
RCT​
Gawdat [11] Egypt Double-blind Full face 1b 1: ID growth 20 41 (35–55) 20 III–IV
split-face factors (meso-
RCT​ therapy)
2: PRP
Kang [13] Korea Single-blind Infraorbital 1b 1: ID PRP on 1: 6 51 (44–57) 16 NR
split-face one side/PPP 2: 10
RCT​ on other
2: ID PRP on
one side/
saline on other
Sevilla [17] India Single-blind NLF 2b 1: Bilateral ID 1: 20 1: ­35c 1: 17 2: 55 II–V
split-face GFC 2: 60 2: ­49c
prospective 2: ID GFC on
comparative one side/ID
cohort PRP on other
Abuaf [3] Turkey Split-face Full face 2b 1: ID PRP 20 44 (40–49) 20 I–III
prospective 2: ID saline
comparative
cohort
Cameli [19] Italy Case series Full face 4 ID PRP 12 45–65d 12 NR
Elnehrawy Egypt Case series NLF (n = 17), 4 ID PRP 20 37c 20 III–IV
[21] CF (n = 14),
Forehead
(n = 8)
Cabrera- Mexico Case series Dorsal hands 4 ID PRP 18 48c 18 NR
Ramirez
[18]

13
 Archives of Dermatological Research

Table 2  (continued)
Source Country Study design Area treated Quality Intervention No. of sub- Age, mean Sex (F) Fitzpat-
­ratinga jects (min–max), rick skin
year type

Sclafani [25] USA Case series NLF 4 ID/SD PRP 15 54c NR NR

Scarano [24] Italy Case series Perioral 4 ID/SD PRP 16 27–60d 16 I–III
(n = 6),
periorbital
(n = 5), full
face (n = 5)
Díaz-Ley Spain Case series Full face 4 ID PRP 9 34–59d 7 NR
[20]
Mehryan Iran Case series Infraorbital 4 ID PRP 10 41 (26–61) NR III–IV
[22] and CF
Redaelli [23] Italy Case series Full face and 4 ID PRP 23 47 (28–70) NR NR
neck
Abdul-Hus- Iraq Case series Full face 4 ID PRP 60 43 (35–50) 60 III–IV
sein [26]
Charles-de- Italy Case series Retroauricu- 4 ID PRP 13 56 (45–65) 11 NR
Sa [27] lar
El-Domyati Egypt Single-blind Full face 1b 1: Dermarol- 1: 8 1: 49 (45–55) 1: 8 III–V
[28] split face ler + topical 2: 8 2: 51 (45–56) 2: 8
RCT​ PRP on right 3: 8 3: 54 (45–59) 3: 8
side/dermarol-
ler only on
left side
2: Dermarol-
ler + TCA
15% on left
side/dermarol-
ler only on
right side
3: Dermarol-
ler + topical
PRP on right
side/dermarol-
ler + TCA
15% on left
side
Everts [29] Portugal Case series Full face 4 ID/SD PRP 11 51 (47–60) 11 II–IV
Fedyakova Spain Case series Neck (n = 10) 4 ID/SD PRP 14 43e (30–60) 14 –
[30] Face (n = 4)
Dorsal hands
(n = 4)
Lee [31] USA Case series Cheeks 4 ID PRP 31 38e (27–71) 29 I–IV

PRP platelet-rich plasma, LOE level of evidence, F females, RCT​randomized clinical trial, Frac. fractional, CO2 carbon dioxide, ID intradermal,
Er erbium, NLF nasolabial folds, CF crows’ feet, SD subdermal, NR not reported, GFC growth factor concentrate, TCA​trichloroacetic acid
a
Quality rating scheme is modified from the Oxford Centre for Evidence-Based
Medicine for ratings of individual studies: (1a) systematic review of RCTs; (1b) individual RCT; (1c) all or none study; (2a) systematic review of
cohort studies; (2b) individual cohort study; (2c) outcomes research; (3a) systematic review of case–control studies; (3b) individual case–control
study; (4) case series; and (5) expert opinion [33]
b
Mean, minimum and maximum age not reported
c
Mean only, minimum and maximum age not reported
d
Mean not reported, minimum and maximum age only
e
Median age

13
 Table 3  Outcome assessment, significant results, and adverse events in included studies
Source Outcomes assessed
PRP in combination with laser resurfacing
Kim and Gallo [14] Patient evaluation of erythema, edema,
pain and pruritus; evaluation of re-
epithelialization, erythema and edema
by blinded plastic ­surgeonb (scale 0–4
[4 = severe])
Na [15] EI and MI by Mexameter; TEWL by
Tewameter; histologic analysis
Shin [16] Patient self-evaluation of texture and
elasticity; correct identification of
post-treatment photos and grading of
­erythemab by 2 blinded dermatologists;
smoothness by Visioscan; hydration by
Corneometer; EI and MI by spectro-
photometer; elasticity by Cutometer;
histologic analysis
Hui [12] Patient self-evaluation (scale 0–3); correct
identification of post-treatment photos
by 2 blinded dermatologists; wrinkles,
texture and pore size by VISIA
PRP in combination with lipofilling
Willemsen [32] Elasticity by Cutometer; NLF depth by
2 blinded ­dermatologistsb (Merz scale
I–V); patient-reported recovery time,
satisfaction (VAS 1–10)
PRP monotherapy
Alam [10] Patient satisfaction; patient evaluation of
pigmentation, texture, wrinkles, and
telangiectasia; evaluation of fine lines,
mottled pigmentation, skin roughness,
and sallowness (scale for each 0–4) by 2
blinded ­dermatologistsb
Gawdat [11] Patient satisfaction; degree of
­improvementb by 3 blinded investiga-
tors with GAIS (scale 0–3); epidermal-
dermal thickness by OCT
Kang [13] Patient satisfaction; degree of
­improvementb by 3 blinded dermatolo-
gists; EI and MI by spectrophotometer
13
Significant results with PRP
↓ Edema and erythema after laser resur-
facing with PRP vs. control
↓ TEWL, erythema and PIH after laser
resurfacing with PRP vs. control
Improvement in skin s­ moothnessd and
laser-associated erythema at 1 month
Greater improvement in elasticity in
the laser-only control group vs. the
topical PRP + laser group. ↑ Number of
fibroblasts and collagen at 1 month vs.
baseline and control
Greater improvement in wrinkles, texture
and elasticity in PRP + laser group vs.
control by patient self-evaluation and by
VISIA for texture and elasticity
↓ Downtime (shorter duration of ery-
thema, edema and crusting) vs. control
Significant reduction in recovery time
in PRP + lipofilling group vs. lipofill-
ing + saline group
Greater improvement in texture and wrin- Mean difference in patient evaluation
kles with PRP vs. control at 6 months by between PRP and control: texture: 0.79
patient self-assessment Wrinkles: 0.73
Improvement in GAIS + epidermal and
dermal ­thicknessf. ↓ Burning sensation
and ↑ satisfaction vs. mesotherapy
Improvement in EI and M ­ Id. Greater
improvement by patient and dermatolo-
gist assessment in the PRP group vs. the
PPP and saline control groups
Quantitative improvement Adverse ­eventsa
Topical PRP + laser vs. laser only: edema: Erythema, edema, pain p­ ruritusc
mean (SE) improvement, 0.13 (0.06)
Erythema: mean (SE) improvement, 0.26
(0.09)
NR Erythema, ­edemac
Archives of Dermatological Research
Topical PRP + laser vs. laser only: skin Erythema, edema, p­ ainc
texture: 100% reported improvement or
much improvement vs. 58%
Smoothness, mean i­mprovementd, 10.3%
vs. 7.5%
Erythema: mean (SD) reduction in EI 1
mo after treatment, 8.4 (0.9)–7.1 (0.9)
vs. 8.0 (0.8)–7.9 (0.9)
Mean (SD), PRP + laser vs. control Erythema, edema, c­ rustingc
Patient self-evaluation: wrinkles 2.3 (0.9)
vs. 2.0 (1.0)
Texture 2.4 (0.8) vs. 2.1 (1.0)
VISIA: texture 1.0 (0.3) vs. 1.2 (0.4)
NR NR
Erythema, edema pruritus, peeling and dry
skin, ­ecchymosise
20% “improved”, 50% “much improved”, Erythema, burning ­sensatione
30% “very much improved” (vs. 35%,
55% and 10%, respectively, in the meso-
therapy group)
Clinical improvement with PRP Erythema, edema, pain, e­ cchymosise
Wrinkles: 19% good, 19% moderate, 50%
mild (vs. saline, 100% no change)
Skin tone: 25% moderate, 44% mild (vs.
saline, 100% no change)
 Table 3  (continued)
Source Outcomes assessed
13
Sevilla [17] Patient satisfaction; GAIS (scale 0–4) by 2 Improvement in GAIS score at 3 monthsd
blinded dermatologists
Abuaf [3] Biopsy with histological analysis
Cameli [19] Improvement by patient and ­investigatorb
(scale; insufficient, sufficient, good or
excellent); smoothness by Visioscan;
elasticity by Cutometer; TEWL by
Tewameter; hydration by Corneometer
Elnehrawy [21] Patient satisfaction; wrinkle ­improvementb Improvement in wrinkle severity (WSRS)
by 2 blinded dermatologists with SHnT
and WSRS
Cabrera-Ramirez [18] Wrinkle severity by Glogau photoaging
and Fitzpatrick wrinkle scales; histologi-
cal analysis
Sclafani [25] Patient self-assessment with GAIS;
­assessmentb by 1 “observer” with WAS
Scarano [24] Patient satisfaction; degree of improve-
ment by investigator evaluation
Díaz-Ley [20] Patient satisfaction; correct identification
of post-treatment photos by 3 blinded
evaluators; histological analysis
Mehryan [22] Patient satisfaction; degree of
­improvementb (scale 0–3) by 1 blinded
investigator; MI by Mexameter; hydra-
tion by Corneometer
Redaelli [23] Patient satisfaction; wrinkle improvement Significance NR
on physician assessment of dermoscopy,
digital camera, and a standardized imag-
ing system photographs using a ‘Special
Spider’ scale
Abdul-Hussein [26] Patient satisfaction; degree of improve-
ment by blinded ­dermatologistsb (scale
0–4)
Charles-de-Sa [27] Biopsy with histological evaluation
Significant results with PRP
Greater improvement in GAIS in the GFC
group vs. PRP group. Results persisted
at 12 months telephone follow-up
↑ In dermal collagen bundles vs. baseline
and control at 1 month
Improvement in skin smoothness, elastic-
ity, barrier function (TEWL), and
­hydrationd
and skin texture (SHnT)d. Greatest
improvement in NLF, followed by
CF, then forehead wrinkles. Greater
improvement in age < 30 years vs.
30–40 years
Improvement in wrinkle severity, ↑ num-
ber of fibroblasts and blood v­ esselsd
Improvement in ­WASd at 2, 6 and
12 weeks follow-up
Significance NR
↑ In epidermal and dermal ­thicknessd.
Greater clinical improvement in those
with photodamage vs. no photodamage
Improvement in infraorbital color
Homogeneityd
Significant improvement in physician
­ratingsd and patient s­ atisfactiond at
3 months
↑ In collagen bundles and elastic fibers in
reticular dermis ↑ dermal ­thicknessd
Quantitative improvement Adverse ­eventsa
Mean (range), PRP vs. GFC: GAIS 0.8 NR
(0–1.7) vs. 1.5 (0.5–2.5)
NR Erythema, ecchymosis, burning sensation
37.5% good, 37.5% sufficient, 25% insuf- Erythema, ecchymosis, burning sensation
ficient
20% of patients had no change, 25% Erythema, pain, tenderness
had < 25%, 30% had 26–50%, 25% had
51–75%
WSRS mean (SD): 2.90 (0.91) at baseline
to 2.10 (0.79) at 2 months
Fitzpatrick, mean (SD): 4.94 (0.80) at NR
baseline to 2.78 (0.42)
Glogau: at baseline 11 patients type III,
7 type II. 7/11 initially type III → II at
1 month f/u, no change in remaining
patients
73% had > 1 point improvement in WAS Erythema, tenderness, ecchymosis
77% had “acceptable” results None
Overall improvement score was 0.3 None
(blinded physicians correctly identified
9 of 27 post-treatment photos)
Fair to good in 80% of patients Burning sensation, ecchymosis
Average degree of improvement: 15–30% Erythema, ecchymosis, burning sensation
(range 6–50%)
33% with ‘mild’, 38% with ‘moderate’, Pain at injection site, ecchymosis
17% with ‘good’ improvement, 5% with
excellent improvement
NR NR
Archives of Dermatological Research
 Table 3  (continued)
Source Outcomes assessed Significant results with PRP Quantitative improvement Adverse ­eventsa

El-Domyati [28] Evaluation of improvement in wrin-
kle appearance, skin texture, overall
improvement by 2 blinded derma-
tologists (scale for each; 0%, 0–25%,
26–50%, 51–75%, 76–100%); histologi-
cal evaluation
Everts [29] Patient satisfaction; antiaging by VISIA-
CR; wrinkle count, depth, and volume
Overall improvement greater with der-
maroller + PRP vs. dermaroller alone
and dermaroller + TCA. Epidermal
thickness ↑ with PRP compared to base-
line and dermaroller alone
↓ Brown spots, wrinkle count, wrinkle
volume; improvement in skin firmness
Mean improvement of 67.75% in der- Erythema, edema, transient pigmentary
maroller + PRP group (25% of patients changes
had 26–50% improvement, 25% with
51–75% improvement, and 44% with
76–100% improvement)
Brown spots: area ↓ 26.3% Mild burning, ecchymosis
Wrinkles: count ↓ 37.2%; volume ↓ 11.5%
Archives of Dermatological Research

by Optical in Vivo Primos; elasticity and erythema; ↑ SLEB thickness Erythema: nasolabial ↓ 29%; malar ↓
by Cutometer; color by Chromameter; 44.3%
thickness and density of SLEB by
ultrasound
Fedyakova [30] Patient satisfaction; degree of improve- Significance NR Moisture mean: 5 Edema, erythema
ment in moisture, elasticity, smoothness, Elasticity mean: 4.8
complexion, wrinkles, by 3 ­physiciansb Smoothness mean: 4.4
(scale for each 0–5); structural assess- Complexion mean: 4.8
ment by ultrasound Wrinkle reduction mean: 4.6
Lee [31] Independent dermatologist and plastic sur- ↑ Satisfaction with facial appearance and WSRS: 3.2% of patients had 1 point Tenderness, tightness, ecchymosis, numb-
geon WSRS and GAIS ­scoresb; patient cheeks (FACE-Q) post-treatment reduction ness edema, erythema, roughness, poor
satisfaction by modified FACE-Qf GAIS: 45.1% of patients had some aes- skin quality
thetic improvement

PRP platelet-rich plasma, SE standard error, EI erythema index, MI melanin index, TEWL transepidermal water loss, NR not reported, SD standard deviation, NLF nasolabial fold, VAS Visual
Analog Scale, GAIS Global Aesthetic Improvement Scale, OCT optical coherence tomography, GFC growth factor concentrate, SHnT Skin homogeneity and texture scale, WSRS Wrinkle Sever-
ity Rating Scale, CF crow’s feet, WAS Wrinkle Assessment Score, SLEB subepidermal low echogenic band
a
No significant or long-term adverse events were reported
b
Assessed via photographic analysis
c
Adverse effects of laser + PRP, all were also noted in the laser + saline control group
d
Compared to baseline
e
Adverse effects of PRP group, all were also noted in the control group
f
The following FACE-Q scales were completed: modified Satisfaction with Overall Facial Appearance scale, modified Satisfaction with Cheeks scale, Psychological Well-Being, Age Appear-
ance Appraisal, and Age-Appearance VAS

13

PRP. Four studies (17%) occurred in the United States [10,
14, 25, 31] and the others in 12 different countries (Table 2).
Each study reported a different method for PRP prepara-
tion (Table 1). Although 50% used commercial kits, only two
kits were used in more than one study, and even those var-
ied with regard to centrifugation. Blood drawn ranged from
3.6 to 50 mL, treatments from 1 to 6, and treatment intervals
from 2 to 12 weeks. Variability was seen in volume of PRP
produced (range 0.2–7 mL) and method of delivery (e.g., topi-
cal vs. injection by micro-ponfi, linear retrograde or fanning)
(Tables 1, 2). In 16 studies (67%), PRP was exogenously acti-
vated, commonly with calcium chloride (11 studies).
Five studies [12, 13, 17, 19, 30] (21%) determined the
platelet concentration of the PRP (range 524–3760 plate-
lets × 109/L), and two reported basal whole blood platelet
concentration [30, 32] (range 212–243 platelets × 109/L).
One [19] reported leukocyte concentration (Table 1).
Outcome assessment
Duration of follow-up was 2 weeks to 1 year
(mean = 12 weeks), with 4 studies (17%) assessing out-
comes at 6–12 months [10, 17, 24, 32]. Ten studies (42%)
used electro-mechanical measurements, and 17 (71%)
used patient-reported outcome measures for satisfaction or
improvement. Skin coloration was the most common device-
measured outcome, assessed in five studies [13, 15, 16, 22,
29], of which two [15, 16] assessed post-laser erythema, two
[13, 22] studied improvement in infraorbital dark circles, and
one [29] measured change in baseline redness. Dermatopa-
thology was performed in seven studies (Table 3).
Twenty studies (83%) used subjective, observer-based
outcomes [10–14, 16–26, 28, 30–32], with 10 (65%)
assessed by blinded physicians [10–14, 16, 17, 20–22, 26,
28, 32]. Among physician-rated outcome measures, the
Global Aesthetic Improvement Scale (GAIS) was most
commonly utilized. Comparing GAIS scores across studies
proved difficult because of scale dissimilarity: some scales
were 0–3 [11, 22], and others between − 1 and 4 [13], 1
and 5 [21], or 0 and 4 [17, 26]. One study was inversely
scored, with 1 corresponding to greatest improvement [31].
Several studies [17, 22, 23] reported only means and ranges
of scores. To facilitate comparisons, global scores were
converted to a standard scale: 0, 0–25, 25–50, 50–75, and
> 75% improvement. Among subjects with scores amenable
to conversion, the average degree of improvement was less
than 50% (80.4% of subjects; 215.5 of 268).
PRP with fractional laser resurfacing for skin
rejuvenation
Four RCTs [12, 14–16] assessed the combination of PRP
with fractional ­CO2 (N = 3) or Er:Glass (N = 1) laser (75
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Archives of Dermatological Research
patients total). Three (75%) delivered PRP by injection [12,
14, 15] and one topically [16]. PRP significantly decreased
the intensity and duration of laser-associated side effects,
including erythema, edema, dyspigmentation, and crusting.
Only some studies reported incremental clinical improve-
ment in skin elasticity with PRP injections and fractional
laser treatment [12], as versus fractional laser alone [16]
(Table 3).
PRP with lipofilling for facial rejuvenation, graft
volume maintenance
One RCT investigated adding PRP to facial lipofilling in the
temporal and midface areas. Although the addition signifi-
cantly reduced postoperative recovery time (mean 15.4 days
versus 9.1 days), it did not improve skin elasticity or increase
volume [32].
PRP as monotherapy for skin rejuvenation
Face and neck
Ten studies (2 RCTs, 1 prospective comparative cohort
study, and 7 CS) evaluated PRP for facial rejuvenation in
180 patients [3, 11, 19, 20, 23, 24, 26, 28–30]. PRP was
injected, except in one study of topical PRP with micronee-
dling [28]. After typically 3 treatments (124/180 patients,
69%) at 4-week intervals (115/180 patients, 64%, Table 1),
in 8 studies involving 144 patients, 90% were satisfied.
Based on pooled ordinal scale data (6 studies, represent-
ing 151 subjects), some degree of physician-rated global
improvement was seen in 75–100% of patients [11, 19, 21,
23, 26, 28]. Specifically, 67% achieved up to 50% improve-
ment, and 33% achieved > 50% improvement.
Improvements in skin elasticity, texture, hydration, wrin-
kles, and micropigmentation occurred 1–3 months after
treatment [19, 23]. In one study, results lasted 6 months
[24] after 3 PRP treatments, with gradual return to baseline.
One CS study [23] on PRP for neck rejuvenation found 28%
improvement 4 weeks after 3 treatments.
Periorbital skin and dark circles
PRP for periorbital wrinkles and dark circles was evaluated
in 75 subjects [13, 19, 21–23] (1 RCT and 4 CS). Fifty-one
subjects (68%) received 3 treatments, and 24 (32%) a single
treatment. Skin texture and patient satisfaction improved
in 64.3–100% [21–23] with crow’s feet (CF). PRP for the
treatment of infraorbital dark circles (26 patients) [13, 22]
resulted in significant improvement in skin color [13, 22]
(Table 3).
Archives of Dermatological Research
Perioral wrinkles
Six studies [17, 21, 23–25, 29] (1 cohort study and 5 CS)
evaluated PRP for perioral wrinkles (128 subjects total).
One [17, 21, 25] to three [23, 24, 29] treatments resulted in
less than 25% [17, 23] and sometimes slightly greater [21]
improvements. Similar degrees of skin firming and redness
reduction were also reported [29].
Forehead wrinkles
Three CS studies [19, 21, 23] (43 subjects) treated forehead
wrinkles with PRP. Typical results ranged from less than
25% [21] to up to 75% [19, 23] improvement.
Cheek wrinkles
One split-face RCT [10] and 2 CS [29, 31] evaluated PRP for
aged cheek skin (61 patients). A single treatment commonly
resulted in statistically significant skin texture improvement
[10, 31]. However, in some cases, blinded patients reported
texture improvement but blinded raters did not [10]. In one
study, while patient satisfaction was improved overall, half
of patients saw no change [31].
Dorsal hands
One CS study [18] addressed photodamaged dorsal hands in
(18 subjects) with 3 monthly treatments. A minority (39%)
initially classified as type III on the Glogau photoaging scale
were reclassified as type II after treatment.
PRP injections vs. saline injections
Serial puncture PRP injections were compared to saline
injections in 127 patients [3, 10, 12–15, 32]. Saline injec-
tions alone resulted in increases in dermal collagen [3]
and improvements in skin sallowness [10]. PRP injections
resulted in significantly greater improvements in skin texture
[10], tone [13], wrinkles [10, 13] and dermal collagen [3]
compared to saline. When used as adjuvant to fractional ­CO2
laser resurfacing, PRP injections resulted in more texture
improvement [12] and decreased the duration and intensity
of laser side effects [14, 15] more than saline. The addition
of PRP injections to lipofilling significantly reduced post-
procedural downtime but did not improve graft volume or
patient satisfaction [32].
Histological analysis
Histological analysis of punch biopsies before and after
PRP (82 subjects) [3, 15, 16, 18, 20, 27, 28] showed that
combining PRP with fractional laser resurfacing resulted
in increased fibroblasts [16], increased collagen volume
and enhanced collagen organization [15, 16], and increased
thickness of the dermal–epidermal junction (DEJ) [16]. PRP
monotherapy increased number of fibroblasts [18, 20, 27],
dermal collagen density [3, 18, 20, 27], elastic fiber deposi-
tion [27, 28], DEJ thickness [20], epidermal thickness [28]
and dermal thickness [27].
The effect of PRP on solar elastosis was inconsistent, with
some studies noting PRP-associated decrease in abnormal
elastotic material [20] and others not [18, 28].
Effect of baseline wrinkle severity
Two studies compared improvement of wrinkles of vary-
ing severity. One [21] reported greater improvement in fine
versus deep wrinkles after one PRP treatment. The other
[18] found greater improvement in more severe wrinkles.
Other, single-arm studies of the effect of PRP on wrinkles
have been similarly equivocal about the types of wrinkles
that respond best [19, 20, 25].
Adverse events
Sixteen studies (320 subjects total) reported mild and tran-
sient adverse events with PRP monotherapy. There were no
reports of infection, scarring or post-inflammatory hyper-
pigmentation. Ten studies [3, 11, 13, 19, 21–23, 26, 29,
31] (223 subjects) reported transient post-injection pain or
burning in approximately two-thirds (n = 150, 67%) lasting
minutes to an hour. Erythema resolving within days was
reported in 10 studies [3, 10, 11, 13, 19, 21, 23, 28, 30, 31],
among 119 of 199 subjects. Ten studies [3, 10, 11, 13, 19,
21, 23, 26, 29, 31] (217 subjects) found bruising/ecchymosis
at injection sites resolving within 2 weeks. Edema [10, 13,
28, 30, 31] and tenderness lasting less than 1 week were less
commonly reported [21, 25, 31]. No serious adverse events
were reported.
Evidence quality
Study quality is assessed in Table 4. All studies evaluating
PRP as adjuvant to fractional laser resurfacing were RCTs
(level of evidence 1B). The consistent benefit detected was
indicative of recommendation grade 1/2A [35]. Studies of
PRP as monotherapy included four split-face RCTs and other
studies, for a collective evidence level of 1B. Studies con-
sistently found improvement with PRP, leading to a recom-
mendation grade of 1/2A [35]. Only one RCT investigated
the effect of PRP during lipofilling, thereby precluding a
recommendation.
13
 Archives of Dermatological Research

Table 4  Quality of evidence for and summary recommendations for included studies
Quality of ­evidencea Strength of Summary of recommendation Source
­recommendationb

PRP in combination with laser resurfacing

Minimization of laser-associated downtime
IB 1/2A ID PRP recommended as adjuvant treatment Kim and Gallo [14], Na [15] and Hui [12]
to fractional laser resurfacing to decrease
the duration and intensity of laser-associated
side effects, especially edema and erythema
Effectiveness in improving facial skin
* * None –
PRP in combination with lipofilling
Reduction of recovery time
IB * ID PRP may reduce recovery time associated Willemsen [32]
with lipofilling, but more studies are needed
Effectiveness in improving facial skin
* * None
PRP monotherapy
Effectiveness in improving the appearance of facial skin
IB 1/2A ID PRP recommended for temporary, modest Abuaf [3], Alam [10], Gawdat [11], Cameli
improvement of overall appearance, texture, [19], Kang [13], Sevilla [17], Abdul-Hus-
and wrinkles in aged facial skin sein [26], Everts [29] and Fedyakova [30]
Effectiveness in improving the appearance periorbital skin and dark circles
IB 2A ID PRP recommended for temporary, modest Kang [13], Cameli [19] and Elnehrawy [21]
improvement of periorbital texture and
wrinkle severity
IB 2A ID PRP recommended for IO dark circles to Kang [13] and Mehryan [22]
temporarily improve pigmentation
Effectiveness in improving the appearance of perioral skin
IIA 2B Based on low-quality evidence, ID PRP Sevilla [17] and Elnehrawy [21] and Everts
may be considered for modest, temporary [29]
improvement of NLF wrinkle severity
Effectiveness in improving the appearance of forehead skin
III 2B Based on low-quality evidence, ID PRP Cameli [19] and Elnehrawy [21]
may be considered for modest, temporary
improvement of forehead wrinkles

PRP platelet-rich plasma, ID intradermal, IO infraorbital, NLF nasolabial folds

*Limited and/or conflicting evidence precludes a recommendation regarding the effectiveness of lipofilling and lasers plus ID PRP for treatment
of visible signs of aging. One small RCT concluded that lipofilling significantly reduced recovery time, but more studies are needed to generate
an evidence-based recommendation
a
Level IA evidence includes evidence from meta-analysis of randomized controlled trials; level IB evidence includes evidence from at least one
randomized controlled trial; level IIA evidence includes evidence from at least one controlled study without randomization; level IIB evidence
includes evidence from at least one other type of experimental study; level III evidence includes evidence from nonexperimental descriptive
studies, such as comparative studies, correlation studies, and case-control studies; and level IV evidence includes evidence from expert commit-
tee reports or opinions or clinical experience of respected authorities, or both [34]
b
1 indicates strong recommendation with high-quality, patient-oriented evidence; 2A, weak recommendation with limited-quality evidence; 2B,
weak recommendation with low-quality evidence [35]

Discussion with gradual return to baseline. When PRP was used as

Despite the high degree of heterogeneity among studies, sig-
nificant improvement from baseline was demonstrated after
treatment with PRP in a preponderance of studies. Global
improvement was modest (up to 50%), but patient satisfac-
tion was high. Improvement typically lasted 3–6 months
adjuvant to laser resurfacing, laser-associated side effects
were decreased in severity and duration. Similarly, adding
PRP to lipofilling decreased recovery time.
Some of the improvement seen following PRP injec-
tions may be due to needle insertion, which may create
microwounds that stimulate collagen production and dermal

13
Archives of Dermatological Research
thickening [36]. Indeed, in some studies [3, 10], saline injec-
tions resulted in increased dermal collagen and improved
skin sallowness, respectively, compared to baseline. In all
the studies, which compared PRP to saline injections, how-
ever, PRP resulted in significantly superior improvement,
which suggests that PRP is markedly more effective than
needling alone.
Few studies assessed topical PRP with fractional resur-
facing or microneedling, respectively. While there may be
some synergistic effects, interstitial fluid and fibrin may fill
open channels shortly after they are created by mechanical
means or energy, thus obstructing uptake [37] and rendering
PRP applied topically less effective than that delivered into
the dermis directly via injection.
Limitations
Failure to report PRP concentration was an important
limitation. Of the five studies reporting concentrations
[12, 13, 17, 19, 30], only two detected concentrations of
at least 1,000,000 platelets/µL [12, 19], the suggested
minimum for effective treatment [38]. The range was wide
(524–3760 × 109/L), with the maximum concentration seven
times the lowest. One study reported leukocyte concentra-
tion and percent yield of platelets [19]. Two studies reported
the platelet concentration of collected blood (range 212–243
platelets × 109/L) [31, 32]. If platelet concentrations were
physiologic (> 100,000 platelets/µL), processed samples
would need to be reduced to less than 10–20% of the original
blood volume to yield PRP with adequate platelet concentra-
tion. Seven studies produced PRP less than 20% of the whole
blood volume [12, 13, 17, 22, 24, 29, 32]. While some have
suggested that high platelet concentrations are not needed
for effectiveness, only one study [13] showed no correlation
between platelet concentration and skin improvement.
Another major limitation is inadequacy and variability in
outcomes assessment. Follow-up assessments occurred as
soon as 2 weeks after treatment, when post-treatment edema
and erythema may have obscured or magnified effective-
ness. Few studies offered follow-up of greater than 6 months.
In some cases, outcomes were assessed through telephone
calls to patients; while telemedicine is resource-conserving
[39], it is unclear that effectiveness can be reliably measured
in this manner, especially since patients were not asked to
transmit standardized “selfies”. The distinct morphologic
features of aging, including skin color and texture, were not
always separately measured [40].
Risk of bias due to lack of blinding was a particular
limitation. While over 80% of studies employed observer-
or clinician-reported assessment scales, only about half
used blinded assessors [10–14, 16, 17, 20–22, 26, 28, 32].
When examining modest effects, unblinded assessors may
evince conscious and unconscious bias, thus potentially
overestimating treatment effectiveness.
Future research
Future studies may determine which aging-specific fea-
tures (e.g., texture versus color) are most responsive to
treatment with PRP and which patient characteristics (e.g.,
age, gender, ethnicity, history of sun exposure) best pre-
dict a favorable response to treatment. The optimal num-
ber of treatments and intervals between them may also be
elucidated.
Several outcomes may be helpful to measure in future
studies: quantification of fundamental PRP parameters
and growth factor concentrations [41–47]; long-term
(≥ 6 months) outcomes; blinded rater assessments; and other
specific agreed-upon (i.e., core) standardized outcomes.
In the absence of better measures for skin aging [48],
comparison of global outcomes on ordinal scales, as in
this review, is all we have. Developing a set of core out-
comes [49–53] and/or a gold-standard instrument for skin
aging would be an improvement. Elicitation of uniform
outcomes across studies would enable pooling of data and
more detailed analysis.
Conclusions
PRP for skin aging is well tolerated [54]. When used in
combination, PRP appears to speed healing after fractional
laser. As monotherapy, PRP does appear to reduce the vis-
ible signs of aging, but the effect size is modest, the dura-
tion of persistence of results uncertain, and much of the
supportive data is from lower quality studies.
Adverse events, in order of frequency, are burning or
warmth, erythema, pain, and bruising. All are mild, tran-
sient, and self-remitting. No serious adverse events were
reported.
This review is limited by the small number of high-qual-
ity studies and the lack of standardized outcomes reporting.
More high-quality RCTs with longer follow-up are needed.
Funding Departmental Research Funds, Dept of Dermatology, North-
western University.
Compliance with ethical standards
Conflict of interest The authors declare that they have no conflict of
interest.
13
 Archives of Dermatological Research

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