International Journal of

Molecular Sciences

Review
The Biological Role of Platelet Derivatives in
Regenerative Aesthetics
Lorena Cristina Santos 1 , Giselle Lobo Lana 2 , Gabriel Silva Santos 2, * , Silvia Beatriz Coutinho Visoni 2 ,
Rayssa Junqueira Brigagão 2 , Napoliane Santos 2 , Rafaela Sobreiro 2 , Andreza da Cruz Silva Reis 2 ,
Bruno Lima Rodrigues 2 , Sabrina Ferrari 2 , Claudia Herrera Tambeli 3, * and José Fábio Lana 2,4,5,6

1 Biomedical Science, Hospital das Clínicas de Goiás, Goiânia 74605-020, Brazil; [email protected]
2 Orthopedics, Brazilian Institute of Regenerative Medicine (BIRM), Indaiatuba 13334-170, Brazil;
[email protected] (G.L.L.); [email protected] (S.B.C.V.); [email protected] (R.J.B.);
[email protected] (N.S.); [email protected] (R.S.); [email protected] (A.d.C.S.R.);
[email protected] (B.L.R.); [email protected] (S.F.); [email protected] (J.F.L.)
3 Institute of Biology, State University of Campinas (UNICAMP), Campinas 13083-862, Brazil
4 Medical School, Max Planck University Center (UniMAX), Indaiatuba 13343-060, Brazil
5 Regenerative Medicine, Orthoregen International Course, Indaiatuba 13334-170, Brazil
6 Clinical Research, Anna Vitória Lana Institute (IAVL), Indaiatuba 13334-170, Brazil
* Correspondence: [email protected] (G.S.S.); [email protected] (C.H.T.)

Abstract: Bioproducts derived from platelets have been extensively used across various medical
fields, with a recent notable surge in their application in dermatology and aesthetic procedures.
These products, such as platelet-rich plasma (PRP) and platelet-rich fibrin (PRF), play crucial roles
in inducing blood vessel proliferation through growth factors derived from peripheral blood. PRP
and PRF, in particular, facilitate fibrin polymerization, creating a robust structure that serves as a
reservoir for numerous growth factors. These factors contribute to tissue regeneration by promoting
cell proliferation, differentiation, and migration and collagen/elastin production. Aesthetic medicine
harnesses these effects for diverse purposes, including hair restoration, scar treatment, striae man-
agement, and wound healing. Furthermore, these biological products can act as adjuvants with
Citation: Santos, L.C.; Lana, G.L.;
other treatment modalities, such as laser therapy, radiofrequency, and microneedling. This review
Santos, G.S.; Visoni, S.B.C.; Brigagão, synthesizes the existing evidence, offering insights into the applications and benefits of biological
R.J.; Santos, N.; Sobreiro, R.; da Cruz products in aesthetic medicine.
Silva Reis, A.; Rodrigues, B.L.; Ferrari,
S.; et al. The Biological Role of Platelet Keywords: platelet-rich plasma; platelet-rich fibrin; growth factors; tissue regeneration; aesthetic
Derivatives in Regenerative medicine
Aesthetics. Int. J. Mol. Sci. 2024, 25,
5604. https://doi.org/10.3390/
ijms25115604
1. Introduction
Academic Editor: Tomoyuki Kawase
Biological products are diverse substances, including vaccines, growth factors, im-
Received: 24 April 2024 munomodulators, monoclonal antibodies, and hematological components. Various studies
Revised: 13 May 2024
have demonstrated the use of numerous biologics in almost every field of medicine. The
Accepted: 16 May 2024
use of autologous hematological components, especially platelet-rich plasma (PRP), has
Published: 21 May 2024
become a highly attractive therapeutic tool for various applications since the biological
functions of these products go beyond hemostasis [1].
According to the International Olympic Committee, PRP is an autologous preparation
Copyright: © 2024 by the authors.
derived from whole blood in which platelets are concentrated in a small fraction of the
Licensee MDPI, Basel, Switzerland. plasma [2] (Figure 1).
This article is an open access article Platelet concentrates carry various growth factors contained in alpha and dense gran-
distributed under the terms and ules. Alpha granules possess seven important growth factors: platelet-derived growth
conditions of the Creative Commons factors (PDGFaa, PDGFbb, and PDGFab), transforming growth factor beta (TGFβ1 and 2),
Attribution (CC BY) license (https:// epithelial growth factor (EGF), and vascular endothelial growth factor (VEGF) [1]. These
creativecommons.org/licenses/by/ growth factors regulate processes such as cell proliferation, matrix remodeling, differ-
4.0/). entiation, angiogenesis, and chemotaxis. Dense granules contain bioactive substances

Int. J. Mol. Sci. 2024, 25, 5604. https://doi.org/10.3390/ijms25115604 https://www.mdpi.com/journal/ijms

 Int. J. Mol. Sci. 2024, 25, 5604 2 of 24

such as ADP, ATP, serotonin, and calcium, which, after activation and subsequent platelet
degranulation, increase membrane permeability and stimulate regenerative processes,
promoting vascular remodeling and immunomodulation through the release of signaling
molecules [1–4]. In addition to these advantages, since platelet-derived bioproducts are
autologous products, they do not present the risk of allergic induction and have been
extensively used in various medical specialties, including cardiac surgery, oral surgery,
orthopedics, sports medicine, and facial plastic surgery. Furthermore, these bioproducts
have undergone a significant upsurge in dermatology and aesthetic procedures in recent
years [5–7]. These biological products have served as regenerative agents for several years,
leveraging growth factors derived from peripheral blood to induce vascularization in dif-
ferent tissues. Upon activation, these cells form a fibrin network in a liquid state, releasing
a plethora of growth factors that foster tissue regeneration by stimulating cell proliferation,
differentiation, and migration and the production of collagen and elastin [8]. These effects
have been explored in aesthetic medicine for different purposes, such as alopecia treatment,
scar treatment, surgery, and wound healing (Figure 2). These products may also be used as
Int. J. Mol. Sci. 2024, 25, x FOR PEER REVIEW 2 of 21
adjuvants in other treatment modalities, including ablative and nonablative laser therapy,
bipolar radiofrequency, and microneedling [9–14].

Int. J. Mol. Sci. 2024, 25, x FOR PEER REVIEW 3 of 21

Figure 1. PRP preparation.

Figure 1. PRP preparation.

Platelet concentrates carry various growth factors contained in alpha and dense
granules. Alpha granules possess seven important growth factors: platelet-derived
growth factors (PDGFaa, PDGFbb, and PDGFab), transforming growth factor beta
(TGFβ1 and 2), epithelial growth factor (EGF), and vascular endothelial growth factor
(VEGF) [1]. These growth factors regulate processes such as cell proliferation, matrix
remodeling, differentiation, angiogenesis, and chemotaxis. Dense granules contain bio-
active substances such as ADP, ATP, serotonin, and calcium, which, after activation and
subsequent platelet degranulation, increase membrane permeability and stimulate re-
generative processes, promoting vascular remodeling and immunomodulation through
the release of signaling molecules [1–4]. In addition to these advantages, since plate-
let-derived bioproducts are autologous products, they do not present the risk of allergic
Figure 2. Application of platelet derivatives in regenerative aesthetics.
induction and have of
Figure 2. Application been extensively
platelet derivativesused in various aesthetics.
in regenerative medical specialties, including car-
diac surgery, oral surgery, orthopedics, sports medicine, and facial plastic surgery. Fur-
Currently,
thermore, these there are different
bioproducts types of PRP
have undergone preparationupsurge
a significant methods infor which parame-
dermatology and
ters suchprocedures
aesthetic as the number of centrifugation
in recent rounds,
years [5–7]. These relative products
biological centrifugal force
have (RCF),
served asand
re-
time can vary.
generative Thisfor
agents influences the platelet
several years, integrity,
leveraging composition,
growth and effectiveness
factors derived of the
from peripheral
product.
blood Additionally,
to induce the variance
vascularization amongtissues.
in different the methods and contents
Upon activation, thesebetween PRP
cells form a
Int. J. Mol. Sci. 2024, 25, 5604 Figure 2. Application of platelet derivatives in regenerative aesthetics. 3 of 24

Currently, there are different types of PRP preparation methods for which parame-
ters such as the there
Currently, number of centrifugation
are different types of PRP rounds, relative
preparation centrifugal
methods forceparameters
for which (RCF), and
time
suchcan
asvary. This influences
the number the platelet
of centrifugation integrity,
rounds, composition,
relative centrifugal andforceeffectiveness
(RCF), and timeof the
product.
can vary. Additionally,
This influences the the
variance
plateletamong the composition,
integrity, methods and andcontents between
effectiveness PRP
of the
product.results
products Additionally, the variance
in different among theand
terminologies methods andmaking
results, contentsstandardization
between PRP productsand re-
results in different
producibility terminologies
challenging [3]. For and results,studies
instance, makinghavestandardization
reported that and
thereproducibility
anticoagulants
challenging [3]. For instance, studies have reported that
used in PRP preparations may also interfere with several processes, such the anticoagulants usedasinwound
PRP
preparations
healing [8]. Formay also reasons,
these interfere with several processes,
platelet-rich such as
fibrin (PRF), anwound healing
alternative [8]. Forconcen-
platelet these
trate, was developed with no additives (anticoagulants) and is produced underwith
reasons, platelet-rich fibrin (PRF), an alternative platelet concentrate, was developed lower
no additives (anticoagulants) and is produced under lower centrifugal forces (Figure 3).
centrifugal forces (Figure 3). This protocol enhances the content and distribution of the
This protocol enhances the content and distribution of the cells and growth factors within
cells and growth factors within PRF matrices. Furthermore, it enables injection in a
PRF matrices. Furthermore, it enables injection in a manner similar to PRP, offering
manner similar
the added to PRP,
benefits offering
of fibrin clotthe added benefits
formation of fibrin
shortly after clot formation
injection shortly
into the target after
tissue.
injection
Its feasibility is attributed to its easy handling and a growth factor content relatively a
into the target tissue. Its feasibility is attributed to its easy handling and
growth factorto
comparable content
those ofrelatively
certain PRPcomparable
products to those of certain PRP products [15].
[15].

Figure 3.3.PRF
Figure PRFpreparation.
preparation.

Consideringthese
Considering thesefindings,
findings, when
when new
new techniques
techniquesareareused,
used,PRP PRPand
anditsits
derivatives
derivatives
can deliver results that meet patient and physician expectations.
can deliver results that meet patient and physician expectations.
Therefore,the
Therefore, the objective
objective of
of this
thisreview
reviewwas
wasto to
highlight the the
highlight rolesroles
of PRP and its
of PRP deriva-
and its de-
tives, including PRF, in aesthetics. This manuscript will also cover their associated benefits
rivatives, including PRF, in aesthetics. This manuscript will also cover their associated
when compared to or associated with conventional treatments.
benefits when compared to or associated with conventional treatments.
2. Methods
A thorough literature review was conducted to offer a comprehensive understand-
ing of the emerging applications of PRP and its derivatives in aesthetic medicine and
dermatology. The PUBMED database was employed from October to December 2023 to
identify relevant reports. The search strategy involved combining the terms “aesthetic use”
with variations of platelet-rich plasma (PRP), including platelet-rich fibrin (PRF), injectable
platelet-rich fibrin (i-PRF), and PRP itself. This search yielded approximately 700 results
(476 for PRP and 210 for PRF). Titles, abstracts, and full texts were meticulously screened
and selected by the authors. A total of 69 articles were included in this study based on their
relevance and publication years, of which 43 were randomized clinical trials, as listed in
Table 1.
Int. J. Mol. Sci. 2024, 25, 5604 4 of 24

Table 1. Baseline characteristics of the randomized clinical trials included in the studies.

Number of Delivery Treatment Clinical

Reference Application Results
Patients Methods Schedule Significance
Increased hair regrowth
Trink, A.; et al. PRP intradermal and decreased hair
Alopecia areata 45 participants 3× monthly Highly significant
(2013) [16] injection dystrophy and burning
or itching sensation.
Complete resolution of
Vazques, O.A.; PRF intradermal
Alopecia areata 1 participant 2× monthly alopecia areata at Highly significant
et al. (2022) [17] injection
6-month follow-up.
Improvement in the
mean number of hairs,
Gentile, P.; et al. Alopecia PRP intradermal with a mean increase of
20 participants 3× monthly Significant
(2015) [18] androgenetica injection 33.6 hairs, and increase
in total hair density of
45.9 hairs per cm2 .
Improvement in anagen
Alves, R. and R.
Alopecia PRP intradermal hairs, telogen hairs, hair
Grimalt (2016) 25 participants 3× monthly Significant
androgenetica injection density, and terminal
[19]
hair density.
An increase of 33.6 hairs
in the target area and a
Gentile, P.; et al. Alopecia PRP intradermal mean increase in
23 participants 3× monthly Significant
(2018) [20] androgenetica injection density of 45.9 hairs
per cm3 compared
with placebo.
Mean hair density on
first visit (before
treatment) was
34.18 ± 14.36/cm2 ,
which was increased to
50.20 ± 15.91/cm2
6 months after first
treatment. Mean scores
Butt, G.; et al. Alopecia PRP intradermal of physician and patient
30 participants 2× monthly Highly significant
(2019) [21] androgenetica injection global assessments were
1.45 ± 0.57 and
1.60 ± 0.62, respectively.
Mean percentage
reduction in hair pulled
was 29.2%.
Terminal-to-vellus hair
ratio was increased in
60% of patients.
Increases in hair count,
hair density, and
percentage of anagen
hairs in the PRP group
Rodrigues, B.L.; Alopecia PRP intradermal versus in the control
26 participants 4× monthly Significant
(2019) [22] androgenetica injection group, without
correlation with platelet
counts or quantification
of the growth factors
in PRP.
There was no significant
difference in hair
Shapiro, J.; et al. Alopecia PRP intradermal
35 participants 3× monthly density change between Useful
(2020) [23] androgenetica injection
the PRP group and
placebo group.
Int. J. Mol. Sci. 2024, 25, 5604 5 of 24

Table 1. Cont.

Number of Delivery Treatment Clinical

Reference Application Results
Patients Methods Schedule Significance
PRP treatment boosted
hair regrowth and
accelerated hair cycling,
and the effect was
sustained for more than
one hair cycle in mice.
Qu, Q.; et al. Alopecia Mice models and PRP intradermal Clinically, mean hair
6× monthly Highly significant
(2021) [13] androgenetica 52 participants injection count, density, diameter,
and anagen hair ratio in
PRP group
showed significant
improvements
compared to
control side.
Increases in percentage
Moftah, N.H.; Female pattern PRP intradermal of terminal hair and
40 participants 3× monthly Significant
et al. (2022) [24] hair loss injection average width of hair
after treatment.
Patients in the
microneedling group
achieved a negative
hair-pulling test and
had improved
perception of hair loss
compared to the
PRP PRP-alone group (82.1%
microneedling vs. 51.9% and 88.0% vs.
Muhammad, A.; Alopecia
60 participants versus PRP 3× monthly 73.9%, respectively). Highly significant
et al. (2022) [25] androgenetica
intradermal The percentage increase
injection in the mean hair count
in the microneedling
group (24.53 ± 9.49%)
was significantly higher
than the increase in the
PRP-alone group
(17.88 ± 10.15%)
(p = 0.011).
Hair-pulling test
became significantly
negative after treatment
(p < 0.05).
Improvements in hair
count, hair density,
terminal hair count, and
terminal hair density in
Three sessions
both groups compared
PRP at 2-week
to pretreatment
microneedling intervals and
Ozcan, K.N.; Alopecia (p < 0.05). Between the
62 participants versus PRP the fourth Highly significant
et al. (2022) [26] androgenetica groups, a statistically
intradermal session 1 month
significant difference
injection after the
was found between the
last session
averages of anagen hair,
telogen hair, and hair
length in the
microneedling-treated
group compared to the
group treated with the
point-by-
point technique.
Int. J. Mol. Sci. 2024, 25, 5604 6 of 24

Table 1. Cont.

Number of Delivery Treatment Clinical

Reference Application Results
Patients Methods Schedule Significance
All patients showed
improvements in hair
count and terminal hair
PRPF
Topical and decreases in telogen
intradermal
minoxidil at 5% hair ratio after
injection versus
twice daily; treatment. The efficacy
Wu, S.; et al. Alopecia 5% topical
75 participants PRPF injection of PRF complex therapy Highly significant
(2023) [27] androgenetica minoxidil versus
performed revealed significant
PRF injection
three times, improvements in hair
combined with
1 month apart count, terminal hair,
minoxidil.
and growth rate,
compared
with monotherapy.
Significant increases in
all patients in hair
density and quantity
after PRP treatment,
PRP intradermal and there was no
PRP treatment
injection significant difference in
thrice monthly;
Wei, W.; et al. Alopecia combined with mean hair diameter.
30 participants minoxidil at 5% Highly significant
(2023) [28] androgenetica 5% topical Hair density/quantity
twice a day for
minoxidil versus was more pronounced
3 months
PRP injections in group with PRP
injections combined
with 5% topical
minoxidil than in group
with PRP alone.
The hair-pulling test,
El-Dawla, R.E.; visual analog scale, and
M. Abdelhaleem, patient satisfaction
Telogen PRP intradermal
and A. 30 participants 4× monthly results showed Significant
effluvium injection
Abdelhamed statistically significant
(2023) [29] differences in
PRP group.
The mean value of the
wrinkle severity was
reduced from
2.90 ± 0.91 before
treatment to 2.10 ± 0.79
Skin Single PRP after 8 weeks of
Elnehrawy, N.Y.; PRP intradermal
rejuvenation 20 participants intradermal treatment. The most Significant
et al. (2017) [30] injection
(wrinkles) injection significant results were
with younger subjects
that had mild and
moderate wrinkles of
the nasolabial
folds (NLFs).
FACE-Q scores showed
improvement at
6 months compared
Mix of PRP and with baseline (44.3 ± 1.9
Skin booster hyaluronic acid at baseline versus
Hersant, B.; et al.
(PRP + 31 participants intradermal 3× monthly 52 ± 3.17 at 6 months). Highly significant
(2017) [31]
hyaluronic acid) injection versus In addition, there was
microneedling an improvement in the
net elasticity parameter
(p = 0.036)
from baseline.
Int. J. Mol. Sci. 2024, 25, 5604 7 of 24

Table 1. Cont.

Number of Delivery Treatment Clinical

Reference Application Results
Patients Methods Schedule Significance
PRP-treated side had
significant
improvements
compared to normal
Skin saline for texture (mean
Alam, M.; et al. PRP intradermal Single PRP
rejuvenation 27 participants self-assessment score, Significant
(2018) [32] injection injection
(cheek rhytids) 2.00 [1.20] vs.
1.21 [0.54]) and wrinkles
(mean self-assessment
score, 1.74 [0.99] vs.
1.21 [0.54]).
Decrease in brown-spot
counts and areas.
Wrinkle count and
volume were
Skin significantly reduced.
Everts, P.A.; P.C. rejuvenation Skin firmness and
PRP intradermal
Pinto, and L. (brown spots, 11 participants 3× monthly redness were Highly significant
injection
Girao (2019) [33] skin redness, significantly improved.
and firmness) The self-assessment at
6-month follow-up
revealed an average
satisfaction score
of >90%.
Improvement in skin
surface spots (p = 0.01),
pores (p = 0.03), skin
texture, wrinkles,
ultraviolet spots, and
porphyrins. Satisfaction
with appearance values
Skin all showed significant
Hassan, H.; D.J. rejuvenation improvements from
Quinlan, and A. (texture, PRF intradermal baseline, including
11 participants 3× monthly Highly significant
Ghanem (2020) wrinkles, injection satisfaction with skin
[34] ultraviolet spots, (p = 0.002), satisfaction
and porphyrins) with facial appearance
(p = 0.025), satisfaction
with cheeks (p = 0.001),
satisfaction with lower
face and jawline
(p = 0.002), and
satisfaction with lips
(p = 0.04).
The symptoms of skin
aging, especially skin
color, pore expansion,
and skin texture,
Erbium
showed improvements,
Cai, J.; et al. Skin fractional laser Two sessions
158 participants according to the Significant
(2020) [35] rejuvenation and topical PRP 2 months apart
evaluation of the
combination
patients and the
physicians of
90.51% and
88.61%, respectively.
Int. J. Mol. Sci. 2024, 25, 5604 8 of 24

Table 1. Cont.

Number of Delivery Treatment Clinical

Reference Application Results
Patients Methods Schedule Significance
Treatment with mixture
of PRP and H.A. led to a
very significant
PRP, hyaluronic improvement in the
acid, and a overall facial
mixture of PRP appearance compared
Hersant, B.; et al.
Skin booster 93 participants and H.A. 3× monthly with treatment with Highly significant
(2021) [36]
intradermal PRP or H.A. alone
injection and (p < 0.0001). Biophysical
micrconeedling measurements also
showed significantly
improved skin elasticity
in this group.
The use of lyophilized
Lyophilized PRP PRP by mesotherapy
da Silva, L.Q.; Skin
19 participants intradermal 2× monthly showed no Significant
et al. (2021) [37] rejuvenation
injection improvement in
skin aging.
Skin Improvement was
rejuvenation Two sessions statistically significant
Banihashemi, M.; PRP intradermal
(periorbital dark 30 participants with a 3-month for dark circles and Highly significant
et al. (2021) [38] injection
circles and interval nasolabial folds
nasolabial folds) (p value 0.025).
The periorbital melanin
Er: YAG laser
in the combined group
and PRP
Skin was significantly
intradermal
Nilforoushzadeh, rejuvenation decreased. Significant
injection or
M.A.; et al. (periorbital hy- 32 participants 3× monthly increase in the skin Highly significant
topical
(2021) [39] perpigmentation lightness and decrease
combination
and wrinkles) in the percent change of
versus Er: YAG
the color and wrinkles
laser alone.
in the combined group.
PRP intradermal Intradermal PRP was
Fourth week
injection versus significantly better than
Mumtaz, M.; and for a total
Melasma 64 participants tranexamic acid intradermal tranexamic Useful
et al. (2021) [40] period of
intradermal acid in management
12 weeks
injection of melasma.
Both modalities yielded
a significant
Skin improvement in
PRP intradermal Two treatment
Diab, H.M.; et al. rejuvenation periorbital wrinkles
40 participants injection versus sessions Significant
(2022) [41] (periorbital after the second session,
plasma gel 4 weeks apart
wrinkles) with significantly better
results on the plasma
gel-injected side.
Both groups showed
statistically significant
Fractional
improvements in all
radiofrequency
parameters. Comparing
Gawdat, H.; et al. Neck microneedling
20 participants 3× monthly the two groups, the Highly significant
(2022) [14] rejuvenation versus in
mean dermal thickness
combination
after treatment was
with PRP
higher in the
combined group.
Int. J. Mol. Sci. 2024, 25, 5604 9 of 24

Table 1. Cont.

Number of Delivery Treatment Clinical

Reference Application Results
Patients Methods Schedule Significance
Both TXA and PRP
were found to be
effective and safe for
melasma, providing
Once every
Tranexamic acid rapid and substantial
Patil, N.K. and 4 weeks for a
(TXA) versus improvement even
A.K. Bubna Melasma 40 participants total of Highly significant
PRP intradermal when used as
(2022) [42] five treatment
injection standalone therapies,
sessions
although PRP was
found to be slightly
better than
intradermal TXA.
PRP was associated
Gonzalez-Ojeda, with decreased intensity
PRP intradermal
A.; et al. (2022) Melasma 20 participants 3× biweekly of the melasma patch Highly significant
injection
[43] and improved
skin quality.
PRP treatment
significantly improved
Skin booster
Shen, J.; et al. PRP intradermal (p < 0.05) the patients’
(coarse pores 90 participants 8× monthly Highly significant
(2023) [44] injection facial skin indicators,
and wrinkles)
quality of life,
and satisfaction.
Noticeable
improvements in deep,
PRF matrix
Mahmoodabadi, fine, and small
Periorbital subdermis
R.A.; et al. (2023) 16 participants 1 session wrinkles, periocular Significant
wrinkles injection using
[45] hyperpigmentation, and
a canola
overall skin freshness at
the injection site.
PRP has efficacy in the
management of atrophic
acne scars. It can be
PRP intradermal
Asif, M.; S. combined with
Atrophic acne injection and
Kanodia, and K. 50 participants 3× monthly microneedling to Significant
scars combined with
Singh (2016) [46] enhance the final
microneedling
clinical outcomes in
comparison with
microneedling alone.
Platelet-rich plasma and
Four sessions subcision showed
on each side of greater improvement
Deshmukh, N.S. PRP injection the face with an (32.08%) in post-acne
and V.A. Atrophic acne into acne scar interval of scars as compared to
40 participants Highly significant
Belgaumkar scars after performing 4 weeks subcision alone (8.33%).
(2019) [47] subcision between Rolling acne scars
two consecutive responded greatest
sessions (39.27%), followed by
box-type scars (33.88%).
Acne scars were
significantly reduced
Krishnegowda, (1.47, SD 0.56) in
PRF intradermal
R.; S.N. Pradhan, comparison to the
Atrophic acne injection
and V.A. 40 participants 4× monthly control side (3.33, SD Highly significant
scars followed by
Belgaumkar 0.53). Patient
microneedling
(2023) [48] satisfaction score was
significantly higher on
PRF side (5.95).
Int. J. Mol. Sci. 2024, 25, 5604 10 of 24

Table 1. Cont.

Number of Delivery Treatment Clinical

Reference Application Results
Patients Methods Schedule Significance
A significant
improvement was seen
in both PRF and PRP
treatment groups. The
PRF and PRP
Diab, N.A.F., therapeutic response
intradermal
A.M. Ibrahim, Four sessions was significantly higher
Atrophic acne injections versus
and A.M. 30 participants with 3-week in the PRF group rather Highly significant
scars PRF and PRP
Abdallah (2023) interval than PRP either alone or
combined with
[49] combined with
microneedling
microneedling. The
combination with
needling increases the
efficacy of PRF and PRP.
CO2 dot matrix laser
combined with PRP can
strongly improve the
clinical efficacy on
patients and shorten the
PRP combined scar-scabbing time and
Guo, R.; et al. Atrophic acne
81 participants with CO2 dot 3× monthly decrustation time, more Highly significant
(2023) [50] scars
matrix laser effectively contributing
to the scar repair,
comfort, skin condition,
psychological state and
satisfaction, and
pain reduction.
Significantly higher
degrees of clinical
PRP intradermal
Neinaa, Y.M.E., improvements were
Stretch marks injection Three treatment
S.F. Gheida, and observed in response to
(striae rubra followed by sessions at
D.A.E. 30 participants treatment sessions by Highly significant
and/or striae fractional CO2 6-week
Mohamed (2021) combining PRP with a
alba) laser or intervals
[51] Fr CO2 laser rather than
pulsed-dye laser.
combining PRP
with PDL.
The combination of an
ablative fractional CO2
Preclaro, I.A.C.,
laser and autologous
E.A.V. Tianco, PRP combined
Stretch marks PRP had better clinical
and M. with fractional
(striae 16 participants 3× monthly improvements and Highly significant
Buenviaje- carbon dioxide
gravidarum) patient satisfaction
Beloso (2022) (CO2 ) laser
compared with an
[52]
ablative fractional CO2
laser and placebo.
PRP with microneedling
was associated with an
improvement in the
skin lesions of striae, a
more significant
Stretch marks
Abdel-Motaleb, PRP combined deposition of collagen
(striae rubra
A.A.; et al. (2022) 40 participants with 3× monthly and elastic fibers, Highly significant
and/or striae
[53] microneedling increased proliferative
alba)
activity in the
epidermis, and
decreased caspase-3
protein expression
values in the epidermis.
Int. J. Mol. Sci. 2024, 25, 5604 11 of 24

Table 1. Cont.

Number of Delivery Treatment Clinical

Reference Application Results
Patients Methods Schedule Significance
Significant decreases in
all striae measurements
were achieved with all
groups (p < 0.001);
PRP intradermal however, the combined
Stretch marks injection, PRP + groups showed greater
Ebrahim, H.M.; (striae rubra subcision, and decreases (p = 0.2 and
75 participants 6× monthly Significant
et al. (2022) [54] and/or striae PRP + combined 0.4). All groups
alba) peeling (GA 70% demonstrated
+ TCA 35%). improvements in
dermal collagen
deposition, which was
higher in the
combined groups.
PRP treatment was
most effective at
reducing the area of
stretch marks, with
consequent stimulation
of the synthesis and
Stretch marks
de Castro PRP remodeling of collagen
(striae rubra 1× weekly over
Roston, J.R.; et al. 12 participants intralesional and elastic fibers. Significant
and/or striae 12 weeks
(2023) [55] injection Additionally, PRP
alba)
promoted an increase in
TLR2 and TLR4
immunoreactivities,
with consequent
increases in TNF-α,
VEGF, and IGF-1.
Significant
improvements in stretch
marks were achieved in
PRP intradermal the group combining
Stretch marks
injection the two techniques
Sayed, D.S.; et al. (striae rubra
30 participants combined with 3× monthly (p = 0.007), and the Highly significant
(2023) [56] and/or striae
fractional CO2 average improvement
alba)
laser. was significantly greater
(60.33 ± 26.49) in this
group (43.80 ± 27.43)
(p value = 0.001).

3. Aesthetic Conditions
3.1. Alopecia
Currently, alternatives for treating hair loss focus on promoting cell proliferation and
differentiation during the growth cycle. The effective pharmacological treatments are
2–5% topical minoxidil, which works through several mechanisms, including arteriolar
vasodilation, anti-inflammatory effects, Wingless and Int-1 gene (Wnt)/β-catenin signaling,
and oral finasteride, which is a selective 5α-reductase type II inhibitor. Although these
drugs improve patients with androgenetic alopecia (AGA), researchers continue to search
for more effective alternatives and limited side effects. For these reasons, due to the
significant ability of PRP to promote tissue regeneration, new treatment protocols have
been developed using this bioproduct, demonstrating efficacy in the treatment of alopecia,
especially in AGA [57].
Although PRP is widely and effectively used to treat hair loss, the exact mechanism
of action of PRP for this purpose has yet to be fully elucidated [58]. It is known that
the hair follicle is a self-renewing mini-organ that undergoes metabolic and morpholog-
ical changes during its cycle. It involves the anagen hair growth phase, the catagen hair
growth phase, the return phase of the cycle, the telogen hair growth phase, and the inactive
phase. PRP can have various effects on hair, and one of the key factors is its antiapop-
Int. J. Mol. Sci. 2024, 25, 5604 12 of 24

totic effect, which is activated by the Bcl-2 protein and Akt signaling. This contributes
to hair growth by increasing the longevity of dermal papilla cells throughout the hair
cycle. Additionally, research has suggested that PRP treatment upregulates the FGF-7/β-
catenin signaling pathway, leading to follicular stem cell differentiation, stimulating hair
growth, and prolonging the anagen phase of the growth cycle. PRP also appears to en-
hance the perifollicular vascular plexus, elevating angiogenic factors such as VEGF and
PDGF [18].
A study on AGA treatment with PRP in rats showed that this biologic product ac-
celerated the hair cycle, suggesting that PRP injections could promote hair growth. To
verify the therapeutic efficacy of PRP in humans, researchers conducted a randomized,
placebo-controlled, double-blinded study with 52 patients with AGA. The study results
demonstrated a substantial increase in the hair density after PRP injections within a short
timeframe. At the 6-month mark, the PRP group exhibited significant improvements in
their hair counts, hair diameters, and proportion of anagen hairs compared to the control
group and baseline measurements [13].
Multiple clinical studies provide evidence supporting the efficacy and safety of using
PRP for treating AGA in men. In a randomized, placebo-controlled study involving 23 male
patients, hair growth parameters were assessed three months after the initial PRP session
and compared with the baseline values in the treated and control areas. The study revealed
significant increases in the average hair count and total hair density in the PRP-treated
area. Microscopic evaluation two weeks after the last PRP treatment indicated increases in
the epidermal thickness in the capillary skin compared to the baseline, accompanied by
a rise in the number of follicles. Additionally, researchers observed an increase in basal
epidermal keratinocytes and follicular bulb cells [18]. These data showed that PRP can be
an effective treatment option for hair loss.
Butt and colleagues [21] evaluated the effectiveness of PRP for hair restoration in
30 patients, including men and women, using various parameters, such as the terminal-to-
vellus hair ratio, the hair density, the hair-pulling test, photographs, the physician global
assessment score, and the patient global assessment score. The authors showed that PRP is
an effective treatment option for androgenetic alopecia, resulting in greater hair density and
physician and patient global assessment scores and an increase in the terminal-to-vellus
hair ratio.
The type of study design directly influences the results. Several split-scalp studies
evaluating intradermal PRP versus saline have shown that PRP improves androgenetic
alopecia, but other studies have failed to prove this. Gentile and collaborators [20] per-
formed a randomized, placebo-controlled trial comparing the hair regrowth of patients
receiving PRP injections via controlled, programmed mechanical injections at a depth of
5 mm using a medical injection gun versus placebo injections. Patients underwent three
sessions, resulting in an increase of 33.6 hairs in the target area and an average increase in
density of 45.9 hairs per cm3 compared to those in the placebo group. Similarly, Alves and
Grimalt [19] conducted a study on twenty-five patients with AGA. They revealed that PRP
treatment has a positive effect on AGA and could even be regarded as a promising therapy
for this disorder.
Conversely, Shapiro et al. [23] analyzed the effect of the intradermal injection of PRP
on hair regrowth and thickness compared with saline. While the hair density significantly
increased in the PRP-treated area compared to the baseline, there was also a modest increase
in the placebo-treated areas. These findings suggest no significant difference in the hair
density changes between the two groups. The variations in the study outcomes may be
attributed to differences in the techniques and types of injections used, influencing the
diffusion and action of PRP. This “design effect” could explain the inconsistent findings
in PRP studies, highlighting the need for additional research to identify factors affecting
treatment outcomes.
Most AGA studies are carried out on men or on groups containing men and women;
however, the effects in these two groups have been yet to be evaluated separately. According
Int. J. Mol. Sci. 2024, 25, 5604 13 of 24

to a meta-analysis assessing the efficacy of PRP separately in men and women, PRP
significantly increased the hair diameter in both sexes, but the hair density was significantly
increased only in men [59]. Although the efficacy of PRP in men and women differed
between the two groups, the administration of PRP was promising in both.
Numerous techniques, including PRP therapy and microneedling, have been em-
ployed individually or in combination to promote hair growth and mitigate hair loss.
Microneedling is based on the premise that limited and controlled injury to the skin trig-
gers a natural healing cascade, provoking the release of growth factors and, therefore,
stimulating the vital dermal structures necessary for hair growth and strengthening. With
this in mind, Muhammad and colleagues compared the efficacies of the combined or iso-
lated application of PRP and microneedling in treating AGA. The group that underwent
PRP application through microneedling experienced a significantly greater average hair
count than the group that received PRP alone. Compared with PRP alone, microneedling
+ topical PRP resulted in a greater increase in the hair count in individuals experienc-
ing hair loss. Combining these two techniques demonstrated synergistic effects and
was proven to be more effective than either method alone, especially in patients with
AGA [25].
A study published in 2021 demonstrated the effectiveness of PRP treatment compared
to intradermal application in AGA patients treated with microneedling. The hair count, hair
density, terminal hair count, and terminal hair density significantly differed between the
two groups and before treatment. A statistically significant difference was found between
the averages of anagen and telogen hair in addition to the hair length in the groups treated
with microneedling [26].
Several authors have combined PRP with other substances to improve the treatment
efficacy of AGA. In a recent study, Wu and collaborators [27] used PRP plus fibroblast
growth factor (PRPF) and minoxidil. In this prospective, randomized, controlled study,
75 patients with AGA were divided into three groups according to the type of treatment
used. In group 1, PRPF was used as a monotherapy through intradermal injections; in
group 2, patients received only 5% topical minoxidil twice a day; in group 3, PRPF injections
were performed in combination with topical applications of minoxidil. All patients treated
with PRPF showed improvements in their hair counts, terminal hair counts, and growth
rates compared to those treated with minoxidil monotherapy.
Wei et al. [28] also compared the efficacy and safety of PRP combined with topical
minoxidil for treating AGA. Thirty male patients were divided into two treatment groups:
the first group received PRP with 5% topical minoxidil, and the second group received PRP
with a topical placebo. The hair density/quantity, clinical efficacy, and patient satisfaction
were more pronounced in the first group. This study showed that the effects of PRP and
minoxidil treatment exceeded those of PRP alone, demonstrating the former as a potentially
beneficial treatment strategy for AGA.
Although the application of PRP in hair loss conditions is mainly based on AGA,
some studies have reported its benefits in other types of alopecia, such as telogen efflu-
vium. Chronic telogen effluvium is characterized by diffuse scalp hair loss. El-Dawla
et al. evaluated the safety and efficacy of different preparation methods of PRP versus a
placebo in thirty women with chronic telogen effluvium. They concluded that PRP can
be acknowledged as an effective therapeutic alternative for patients with chronic telogen
effluvium [29]. Moftah and colleagues [24] studied different PRP preparation protocols
regarding the number of spins, centrifugal force, type of centrifuge, and tube size to evalu-
ate which protocol has better clinical efficacy in treating female pattern hair loss (FPHL).
Patients were divided into four groups as follows: one spin using a centrifugation force
of 1000× g for 10 min; two spins using a centrifugation force of 250× g for the first and
450× g for the second, both for 10 min; two spins with a centrifugation force of 250× g
for the first and 1000× g for the second, both for 10 min. All of these groups used small
sodium citrate tubes (2 mL VACUTEST tubes, Buffered Citrate 9NC 3.2%, made in Italy)
and a non-digital centrifuge (Electronic Centrifuge 80-1; maximum speed: 4000 rpm; timer
Int. J. Mol. Sci. 2024, 25, 5604 14 of 24

range: 0–60 min; capacity: 20 mL × 6; made in China). In the last group, PRP was prepared
with one spin, using a centrifugation force of 220× g for 10 min, with a large sodium citrate
tube (9 mL VACUETTE tube, 9NC coagulation sodium citrate 3.2%, made in Austria) and a
digital centrifuge (HERMLE z 326 k centrifuge; maximum speed: 18,000 rpm; maximum
capacity: 4 × 100 mL; timer: from 10 s to 99 min; temperature range: from −20 to 40 ◦ C;
made in Germany).
This study revealed that the PLT was lower in groups I, II, and III, in which a non-
digital centrifuge was used at a high rotation speed with small sodium citrate tubes.
Conversely, protocols using a digital centrifuge, large sodium citrate tubes, and a low-
speed spin (220× g) were more effective at preparing PRP. These findings support existing
research suggesting an inverse relationship between the platelet count and centrifugation
speed. In terms of efficacy, a study revealed that PRP is effective and safe for treating female
pattern hair loss (FPHL), as all patients exhibited statistically significant increases in their
percentages of terminal hairs and average hair widths after treatment [24].
To investigate whether the discrepancies in the results reported in the literature re-
garding PRP in patients with androgenetic alopecia could be linked to the protocol used
and correlated with the platelet and growth factor levels, Rodrigues et al. conducted an
analysis of the platelet count and growth factor levels in PRP and their correlation with hair
growth. In this study, 26 patients were randomly assigned to receive four subcutaneous
injections of either PRP or saline. The authors observed the favorable use of PRP as a
therapeutic alternative for treating androgenetic alopecia, but no association was found
between the platelet count and the evaluated growth factors. The conclusion was that
clinical improvement might be associated with other mechanisms [22].
Rinaldi and collaborators compared the efficacy and safety of PRP with those of
triamcinolone acetonide (TrA) or a placebo in 45 patients with alopecia areata (A.A.).
Patients who underwent PRP treatment exhibited significantly greater hair regrowth than
those treated with the TrA or placebo. The study revealed that 38% and 71% of patients in
the TrA group experienced regression at the 6th and 12th months, respectively. In contrast,
no patients in the PRP group experienced recurrence at 6 months, and only 31% did so
at 12 months. Overall, 96% of patients in the PRP group achieved the regrowth of fully
pigmented hair from the initiation of hair growth. In contrast, only 25% of patients in the
TrA group had pigmented hair at the beginning of hair growth [16].
Furthermore, Vazques et al. [17] evaluated PRF for the treatment of A.A. in a 28-year-
old patient who developed this condition after a symptomatic COVID-19 infection. He
underwent two PRF intradermal sessions, the first in March and the second in May, at
which point his A.A. resolved at the 6-month follow-up. The authors concluded that PRF
for A.A. is a promising treatment for patients with this autoimmune disease.
PRP and PRF, used alone or in combination with various protocols, techniques, or
other agents, such as 5% minoxidil, appear promising for treating different types of alopecia
or hair loss in both men and women. However, factors such as the study design, PRP
preparation protocols, nature and severity of the disease, PRP diffusivity, and potential as-
sociations with other substances can impact the quality of the results. Consequently, further
research is needed to establish a standard protocol that optimizes treatment outcomes.

3.2. Skin Rejuvenation

The demand for aesthetic procedures, particularly rejuvenation, has steadily increased
in recent years due to the aging global population. Skin aging is influenced by intrinsic
factors, such as genetic background and chronological age, as well as extrinsic factors,
such as exposure to ultraviolet radiation, trauma, air pollution, alcohol consumption,
nutritional issues, smoking, and reactive oxygen species causing DNA damage. These
factors contribute to decreased or hyperexpression in melanocytes, reduced fibroblast
activity, and diminished collagen and elastin synthesis, leading to dermal disruption and the
dysregulation of the stem cell population responsible for tissue repair [60,61]. Subsequent
skin changes involve hyper- or hypopigmentation, skin laxity, and the development of both
Int. J. Mol. Sci. 2024, 25, 5604 15 of 24

superficial and deep wrinkles, significantly impacting self-image and social acceptance [62].
Regarding rejuvenation, the primary goal is to counteract or minimize the aging process
using either surgical or noninvasive methods. As the demand for aesthetic procedures to
prevent related changes and enhance skin quality has risen, there has been a notable decline
in the number of patients opting for surgical interventions [61]. Among the nonsurgical
aesthetic procedures, PRP has been extensively researched and has yielded favorable
results with high patient satisfaction and no significant adverse effects [62]. PRP offers
numerous benefits in facial rejuvenation, addressing concerns such as atrophic acne scars,
pigmentation disorders, wrinkles, folds, loss of elasticity, and tissue volume loss. The exact
mechanism of action of PRP and its derivatives in facial rejuvenation has yet to be fully
understood. It is hypothesized that the growth factors in PRP may facilitate tissue repair,
increase cell proliferation, and influence the expression of differentiation genes. This, in
turn, supports angiogenesis and cellular rejuvenation processes, potentially leading to
more enduring effects than other procedures [63]. In vitro studies have indicated that PRP
may enhance collagen expression, remodel the extracellular matrix, promote fibroblast
proliferation, and facilitate fibroblast differentiation into myofibroblasts [64].
The application of PRP and its derivatives is intended to improve the skin quality,
texture, and tone via injection or topical application combined with microneedling ei-
ther individually or in combination with other aesthetic procedures. Banihashemi and
colleagues [38] tested two sessions of pure PRP with a 3-month interval for facial rejuve-
nation in 30 female participants. According to patient reports, they observed significant
improvements in periorbital dark circles and nasolabial folds. They concluded that facial
rejuvenation with PRP is an effective and noninvasive technique.
Among the different types of wrinkles, periorbital wrinkles are the most common
and challenging to rejuvenate, as the periorbital skin is thinner. Considering that PRP and
plasma gel have been used for skin rejuvenation, Diab and colleagues compared the use of
both products for periorbital wrinkles in 40 female patients. The PRP and plasma gel were
injected into each side of the face during two treatment sessions four weeks apart. Patients
were followed up 2 weeks after each treatment session and 12 weeks after the last session.
The authors showed that after the second session, both modalities had significantly im-
proved periorbital wrinkles, achieving superior results with the plasma gel. However, they
were not able to ameliorate periorbital hyperpigmentation [41]. However, Nilforoushzadeh
et al. showed that the combination of an erbium-doped yttrium aluminum garnet (Er:
YAG) laser and PRP is significantly more effective for periorbital hyperpigmentation and
wrinkles than Er: YAG laser monotherapy [39].
Similarly, in a prospective clinical trial, Mahmoodabadi and colleagues verified the ef-
fectiveness of PRP and its derivatives in treating periorbital wrinkles [45]. PRF was injected
into the periorbital regions of 15 volunteers. The results demonstrated improvements in
deep, delicate, and small wrinkles, periorbital hyperpigmentation, and the overall freshness
of the skin at the injection site. Participants reported swelling at the injection site lasting up
to one day after the procedure, which resolved on its own without any complications.
Based on the evidence that PRP conveys favorable results for hyperpigmentation
treatment, Gonzalez-Ojeda and colleagues [43] studied the role of PRP in treating melasma.
Twenty female patients with melasma underwent three intradermal PRP sessions at an inter-
val of 15 days, which were evaluated before and after treatment. Comparisons were made
regarding the concentration of melanin in the treated area, the severity index score, the de-
gree of patient satisfaction, and the degree of histological changes. Through dermatoscopy
examinations, decreases in pigmentation after treatment with PRP and histopathological
improvements were reported. Reductions in skin atrophy, solar elastosis, and inflammatory
infiltration were also observed.
Several cosmetics and chemical peels, including tranexamic acid, constitute the ther-
apeutic armamentarium for treating melasma with some success. Therefore, Patil and
Bubna [42] compared the benefits and safety of tranexamic acid (4 mg/mL) versus PRP
for melasma treatment. In total, 40 patients with melasma were randomly distributed
Int. J. Mol. Sci. 2024, 25, 5604 16 of 24

into two groups and received either tranexamic acid or PRP. Patients received weekly
intradermal injections for one month, totaling five injections. No significant adverse effects
were found in either group, and both had rapid or substantial improvements in melasma,
demonstrating that these agents are effective and safe therapeutic options for this disease.
Mumtaz et al. compared the effectiveness of PRP to that of tranexamic acid (4 mg/mL)
in the treatment of melasma, obtaining superior results with PRP. The authors divided
64 patients with melasma into two groups: one with 1 mL of PRP and one with intradermal
tranexamic acid. Treatment was offered every four weeks for twelve weeks, and the final
result was observed in the 24th week [40].
Since PRP has potential benefits for facial skin rejuvenation, it has been used in several
investigations. A study examined the effectiveness of PRP intradermal injections for facial
rejuvenation through biometric parameters and patient satisfaction. Significant reductions
in the number and area of blemishes, decreases in the count and depth of wrinkles, and
improvements in the redness and firmness of the skin were observed. Regarding the patient
satisfaction index, after six months, an average score greater than 90% was achieved [33].
A similar study evaluated the efficacy and safety of intradermal PRP injections for reju-
venation and wrinkle treatment in 20 patients with different types of wrinkles. In this
investigation, the intradermal injection of PRP was well tolerated and capable of rejuvenat-
ing the face, promoting the significant correction of wrinkles, especially in the nasolabial
folds [30].
When combined with other skin-boosting biomolecules, such as hyaluronic acid,
PRP has emerged as an effective treatment for enhancing the skin quality, addressing
bleeding, and combating signs of aging. An extensive study involving 80 patients with
facial aging examined the clinical efficacy, adverse reactions, and durability of PRP + skin
booster effects. Over a year of observation, patients reported positive changes in their
skin condition, enhanced quality of life, and increased satisfaction with their appearance
following treatment. The study concluded that PRP + skin booster was effective and
safe at alleviating issues such as coarse pores and wrinkles, contributing to overall facial
rejuvenation. These findings offer compelling evidence supporting the clinical application
of PRP in skin booster treatments [44].
Hassan et al. focused on testing injectable platelet-rich fibrin (i-PRF) for facial skin
rejuvenation. The study reported significant improvements in various skin parameters,
including surface spots, pores, wrinkles, ultraviolet spots, skin texture, and porphyrins,
at the 3-month follow-up. Patient satisfaction with appearance also showed substantial
enhancements, particularly regarding skin quality and overall facial appearance, covering
areas such as the cheeks, lower face, jawline, and lips. Notably, the study highlighted the
safety and effectiveness of intradermal i-PRF, emphasizing increased patient satisfaction
without significant adverse effects [34]. In contrast, Silva and collaborators used lyophilized
PRP because the facility needed to obtain numerous samples via single venipuncture, which
is helpful for multiple injections. The authors evaluated the effect of this preparation by
monthly intradermal injections compared with saline in treating skin aging through a
phase II pilot study. They found that applying freeze-dried PRP via mesotherapy did not
improve skin aging [37]. A split-face study comparing the benefits of PRP on photoaged
skin with those of saline control skin in male and female participants with bilateral cheek
rhytids was performed by Alam and colleagues. The average photoaging scores related
to fine lines, mottled pigmentation, roughness, and pallor, reported by two dermatolo-
gists, showed no significant differences between the PRP and control groups. However,
patient satisfaction regarding texture, wrinkles, pigmentation, and telangiectasias was
more significant in the PRP-treated group [32]. These controversial studies show that
the lack of standardization may interfere with the quality of the results from using PRP
in aesthetics.
Clinical evidence indicates that PRP can be utilized independently or with lasers,
microneedling agents, or other substances, such as hyaluronic acid. Combining hyaluronic
acid with PRP may amplify the release and retention of growth factors, enhancing collagen
Int. J. Mol. Sci. 2024, 25, 5604 17 of 24

synthesis and stimulating fibroblast activation, thereby contributing to skin rejuvena-

tion [31]. A prospective, open-label study by Hersant et al. aimed to showcase the clinical
advantages of combining PRP and hyaluronic acid. The study, utilizing FACE-Q scores
and biophysical measurements, revealed a substantial improvement at the 6-month mark
compared to the baseline [36].
A study carried out in Korea showed that PRP combined with a fractional laser
increased patient satisfaction and skin elasticity and decreased the rate of erythema. It
also increases the cohesion of the dermal epidermis, the amount of collagen fibers, and the
number of fibroblasts [65]. Gawdat et al. compared fractionated radiofrequency (fr-RF)
microneedling alone and in combination with PRP for rejuvenating the neck region. The
combined treatment showed an overall improvement in the appearance of the neck, as
evidenced by the statistically significant increase in the dermal thickness, moderate-to-
excellent results according to a medical evaluation by the Global Aesthetic Improvement
Scale (GAIS), and great patient satisfaction [14].
PRP and its derivatives associated with other rejuvenation techniques optimize the
results and reduce the side effects of some methods, accelerating the regeneration process.
One of these associations was demonstrated by Cai et al. [35], who attempted to evaluate
whether PRP could improve the restorative effects of erbium fractional laser treatments.
This procedure is widely used because it considerably improves skin aging, but it is
associated with several side effects, such as erythema and pigmentation. They concluded
that erbium fractional laser irradiation combined with PRP application is an effective and
safe option for improving aging facial skin, with minimal side effects, suggesting the use of
the combination instead of the laser alone.
Atrophic acne scarring presents a therapeutic challenge in aesthetic medicine, but
various modalities are available to address this concern. These include microneedling,
radiofrequency, fractional lasers, punch excision, suturing, subcision, and dermabrasion, as
well as autologous fat grafting, autologous dermal grafts, and autologous PRP and PRF [66].
Cho and colleagues [67] evaluated the effects of PRP in vitro on the activation of dermal
fibroblasts through extracellular matrix remodeling. Cell proliferation and migration
assays, an ELISA, and Western blotting revealed that PRP elevated the expression of type I
collagen, elastin, and matrix metalloproteinases 1 and 2, thereby expediting the wound-
healing process. These results offer valuable insights into the potential mechanisms by
which PRP facilitates tissue remodeling, suggesting its applicability in addressing aesthetic
dysfunctions such as acne scars.
PRP and microneedling have gained popularity as off-label treatments for rejuvena-
tion and body repair. In aesthetic medicine, they represent comprehensive and informed
resources. A recent study involving 40 patients with atrophic acne scars compared the
efficacy of autologous i-PRF + microneedling to that of microneedling alone. The area
treated with i-PRF exhibited a significant reduction in acne scarring, and the mean pa-
tient satisfaction score was notably greater [48]. Asif and colleagues [46] conducted a
split-face comparative study to treat atrophic acne scars, comparing PRP + microneedling
versus microneedling + distilled water. In the PRP + microneedling group, 40% of pa-
tients reported “excellent” results, while 60% rated the results as “good”. The study con-
cluded that the combination of PRP and microneedling is significantly more effective than
microneedling alone.
Acne scars are among the most common aesthetic dysfunctions that can affect self-
esteem and quality of life. Therefore, there is a rising demand for treatment alternatives that
can minimize or ameliorate this disorder. An experimental analytical study was conducted
on 40 patients to compare PRP administration after subcision for acne scars. The right side
of the face was injected with autologous PRP into each scar after performing subcision.
The left side of the face was the control, where only subcision was performed. PRP +
subcision led to superior results in post-acne scars compared to subcision alone. They
concluded that PRP and subcision act synergistically to improve the appearance of acne
scars [47].
Int. J. Mol. Sci. 2024, 25, 5604 18 of 24

Diab et al. performed a comparative study using PRF versus PRP and intradermal
application and microneedling to treat atrophic acne scars. The participants were allocated
into two groups, with each receiving treatments on each side of the face. The left side of
the face received the intradermal injection of PRP (group 1) or PRF (group 2), and the right
side received topical PRP or PRF followed by microneedling. No significant differences in
the acne scar severity were observed on either side of the face. However, the improvement
in the PRF group, either alone or combined with microneedling, was significantly greater
than that in the PRP-only group [49].
The CO2 dot matrix laser is a widely used method for treating acne scars, and its effects
have been reported in several studies. However, one of the limitations of this technique
is its high cost. Furthermore, the effectiveness of this method depends mainly on the
penetration capacity of the laser, the homogeneous energy distribution, and the excessive
thermal coagulation, which can cause adverse reactions, such as thermal damage and
pigmentation of the patient’s skin [68]. Guo and colleagues studied the clinical efficacy and
safety of a CO2 dot matrix laser combined with PRP. They concluded that combining the
two techniques can strongly improve the scar repair efficacy and psychosocial health and
quality of life in patients with acne scars [50].

4. Striae
Striae distensae (S.D.) are commonly referred to as stretch marks. S.D. manifest
clinically as parallel striae perpendicular to the skin’s tension lines. These tumors resemble
dermal scars histologically and are often associated with factors such as pregnancy, obesity,
hormonal changes, and genetic predisposition, primarily affecting females. There are two
types of stretch marks based on their clinical and histopathological features and categorized
by their maturation stages. In the initial stage, stretch marks known as “striae rubra” (S.R.)
manifest as immature, tense, and erythematous lesions due to the reorganization of and
reduction in elastin and fibrillin fibers and the structural changes in collagen. Over time,
they progress to the atrophic and hypopigmented stage and are then referred to as “striae
alba” (S.A.), characterized by the local breakdown of elastin and collagen with mast cell
enzymes released in the mid-dermal tract [69,70].
Various treatment modalities, including different types of lasers (pulsed-dye, frac-
tional CO2 , Nd YAG, Er Glass, Er YAG, and diode lasers), radiofrequency, microdermal
abrasion, carboxytherapy, chemical peels, and topical cosmetics such as sodium ascorbate
and tretinoin, have been explored in numerous studies, yielding variable results for the
treatment of stretch marks. However, these methods have not yet been proven to be suf-
ficiently compelling and have minimal adverse effects. Leveraging the well-established
biological effects of PRP, this biological tool has emerged as a promising option for treating
stretch marks, either as a standalone therapy or in combination with other alternatives [70].
To confirm this hypothesis, de Castro and colleagues [55] subjected patients with abdominal
striae to intralesional PRP injections to characterize and compare the structural changes in
the collagen and elastic fibers in these areas. Furthermore, the authors suggested that this
treatment’s possible mechanisms of action were related to signaling pathways involving
Toll-like receptors (TLRs) and growth factors. Biopsies of the treated areas were conducted
at the initiation of treatment and at weeks 6 and 12 posttreatment, revealing the effective-
ness of PRP in reducing the area of stretch marks. This reduction was accompanied by
the stimulation of collagen and elastic-fiber synthesis and remodeling. Moreover, PRP
increased the immunoreactivities of TLR2 and TLR4, subsequently increasing the TNF-α,
VEGF, and IGF-1 levels. These findings underscore PRP’s promising therapeutic potential
for treating stretch marks.
Another recent study described and analyzed stretch-marked-derived fibroblasts
(SMFs) subjected to two in vitro treatments: sodium ascorbate and PRP. The type I collagen
expression was measured before and after adding different concentrations of PRP and
sodium ascorbate to the culture medium. This study demonstrated that SMFs treated with
both substances exhibited increases in type I collagen expression and cell proliferation.
Int. J. Mol. Sci. 2024, 25, 5604 19 of 24

After 24 h of incubation with 1% PRP or 5% PRP + sodium ascorbate, the cell viability
increased by 140% and 151%, respectively, and it increased by 156% and 178%, respectively,
after 48 h. These results showed that both treatments were effective and suggested that the
improvement in stretch marks mediated by the metabolic activity of SMF was viable [71].
In light of the information above, it is evident that the utilization of PRP can play a
crucial role in treating stretch marks. This process appears to be mediated by the release of
growth factors that act on the proliferation of fibroblasts, accounting for tissue repair and
the production of collagen and elastic fibers. Based on these hypotheses, Abdel-Motaleb [53]
assessed whether incorporating PRP would enhance the efficacy of microneedling in ad-
dressing stretch marks. Forty individuals with stretch marks were separated into two
groups: those receiving microneedling alone or those receiving microneedling in con-
junction with PRP. The study findings indicated that the combined therapy resulted in
the superior enhancement of skin lesions, improved collagen and elastic-fiber deposition,
heightened fibroblast proliferative activity, and the reduced expression of the caspase-3
protein in the epidermis.
Various kinds of lasers, such as fractional CO2 lasers, are effective for S.D. To evaluate
the synergistic effect of this laser alone with PRP in S.D. treatment, Sayed et al. [56]
compared the efficacy of a fractional CO2 laser alone versus a CO2 laser + PRP in S.D.
treatment. They studied this effect in thirty adult female patients with S.D. divided into
two groups: laser monotherapy or laser + PRP. Skin biopsies were taken from the lesions
before and after treatment for histopathological evaluation. The authors observed that
the combined treatment was more effective than the fractional CO2 laser alone. Similarly,
Neinaa and colleagues [51] evaluated the synergistic effect of a fractional CO2 and pulsed-
dye laser (PDL) with PRP in thirty S.D. patients. Patients received an intradermal injection
of PRP on both sides, followed by a fractional CO2 laser on the right side and a PDL on the
left side. The patients received three treatment sessions at 6-week intervals. The authors
observed that both treatment sides had significantly improved clinical S.D. lesion outcomes;
a significantly greater degree of clinical improvement with better outcomes and fewer side
effects were observed in response to the PRP + fractional CO2 laser irradiation than in
response to the PRP + PDL.
However, Preclaro and colleagues [52] also studied the synergistic effect of a fractional
CO2 laser with PRP, albeit in striae gravidarum (S.G.), a connective-tissue dysfunction
commonly observed in primigravidae. They evaluated 16 patients with S.G. treated with a
fractional CO2 laser followed by PRP on one side of the abdomen and with a fractional CO2
laser followed by normal saline on the other. The study was performed in three sessions at
4-week intervals and showed that the combination of an ablative fractional CO2 laser and
autologous PRP was superior regarding the clinical improvement and patient satisfaction
score, but the outcome measures were not significantly different. These findings may
suggest that differences in the protocols or types of striae may interfere with the synergistic
effects of PRP and other treatments.
Ebrahim et al. [54] compared the efficacy and safety of PRP monotherapy versus PRP +
subcision or medium-depth peeling (70% glycolic acid followed by 35% trichloroacetic acid)
in seventy-five female patients with S.D. They concluded that using PRP in combination
with subcision or peeling was more effective than using PRP alone.

5. Authors’ Note: Choosing between PRP and i-PRF for Aesthetic Procedures
Physicians often face the dilemma of selecting the most suitable platelet derivative for
aesthetic procedures. Recent studies have shed light on the comparative effectiveness of
PRP and i-PRF in promoting skin rejuvenation and enhancing aesthetic outcomes.
One study [72] demonstrated that i-PRF stimulates greater dermal skin fibroblast cell
migration and proliferation and collagen synthesis compared to PRP. The study found
that all platelet concentrates were non-toxic to cells and promoted high cell survival
rates. Fluid-PRF showed significant advantages over the PRP and control groups: skin
fibroblasts migrated over 350% more compared to the control and 200% more compared to
Int. J. Mol. Sci. 2024, 25, 5604 20 of 24

the PRP group, induced greater cell proliferation at 5 days, and resulted in significantly
higher mRNA levels of TGF-beta, collagen 1, and fibronectin compared to the PRP group.
Additionally, fluid-PRF demonstrated a significantly greater ability to induce collagen
matrix synthesis than PRP. This finding underscores the potential superiority of i-PRF in
promoting tissue regeneration and enhancing aesthetic results.
Moreover, a comprehensive review [7] highlights an important consideration regarding
the diffusibility of PRP and the durable scaffolding effect of fibrin from PRF. The therapeutic
value of PRP, known for its diffusible nature, may sometimes be hindered depending on
the injection site. In contrast, i-PRF offers a natural product with no anticoagulant needed,
minimizing the interference with natural biochemistry and lowering costs. However, i-
PRF does require a more experienced operator due to the technical complexities in its
preparation. The operator must collect blood quickly and centrifuge it immediately to
avoid premature coagulation, ideally within 2 min and 30 s [7]. Despite these challenges,
i-PRF presents a more feasible treatment alternative, particularly in procedures requiring
enhanced tissue regeneration and longevity.
In light of these findings, physicians should carefully consider the specific require-
ments of each aesthetic procedure and the desired outcomes when choosing between PRP
and i-PRF. While PRP may offer potent signaling effects, i-PRF’s durable scaffolding effect
and superior cell stimulation properties, along with its feasibility and cost-effectiveness,
make it a promising option for achieving optimal aesthetic results.
Ultimately, the decision between PRP and i-PRF should be guided by a thorough un-
derstanding of their properties, mechanisms of action, and clinical evidence, in conjunction
with the individual needs and goals of each patient.

6. Conclusions
While the literature underscores the potential benefits of PRP and PRF in addressing
various aesthetic concerns, such as wrinkles, skin texture, hair loss, acne scars, and hyper-
pigmentation, challenges persist within the field. The lack of standardized protocols for
PRP and PRF preparation remains a significant impediment, leading to variability in the
methods and concentrations across studies and hindering consistency and efficacy.
The absence of an official PRP protocol for precise goals is due to various factors,
primarily the lack of standardization in PRP preparation methods. Variability in techniques,
such as centrifugation and anticoagulants, leads to diverse platelet concentrations and
growth factor compositions, hindering uniform treatment outcomes. Additionally, the
diverse applications of PRP across medical specialties require tailored protocols. Different
treatment objectives, such as orthopedic versus dermatological applications, necessitate
specialized formulations and delivery methods. However, consensus on optimal PRP
formulations remains elusive due to the complex interplay of variables.
Despite these hurdles, PRP and PRF offer promising, minimally invasive treatments
for aesthetic concerns. However, the reliance on small sample sizes in some studies
underscores the challenges in drawing robust conclusions from the available evidence.
While the evidence suggests a promising role for PRP and PRF, it is essential to acknowl-
edge the limitations inherent in the current body of literature. Moving forward, efforts
to address these challenges will be crucial in advancing the field and ensuring the re-
producibility and reliability of outcomes. To establish standardized PRP protocols, col-
laborative efforts among stakeholders are crucial. Consensus guidelines, informed by
empirical evidence from clinical trials, are needed to address this challenge. Technological
advancements, such as automated processing systems, may offer potential solutions to
enhance standardization.
In conclusion, while PRP and its derivatives hold significant promise as minimally
invasive treatments for various aesthetic concerns, addressing the current challenges and
uncertainties surrounding their use is paramount. By fostering collaboration and driving
innovation, the aesthetic medicine community can overcome these challenges and realize
the full potential of PRP and i-PRF in enhancing patient outcomes and satisfaction.
Int. J. Mol. Sci. 2024, 25, 5604 21 of 24

Author Contributions: Conceptualization, L.C.S., G.S.S. and B.L.R.; methodology, G.S.S. and N.S.;
validation, S.B.C.V., R.J.B. and G.L.L.; investigation, A.d.C.S.R. and R.S.; data curation, C.H.T.;
writing—original draft preparation, G.S.S.; writing—review and editing, B.L.R.; visualization, S.F.;
supervision, S.F.; project administration, J.F.L. All authors have read and agreed to the published
version of the manuscript.
Funding: This research received no external funding.
Conflicts of Interest: The authors declare no conflicts of interest.

References
1. Dos Santos, R.G.; Santos, G.S.; Alkass, N.; Chiesa, T.L.; Azzini, G.O.; da Fonseca, L.F.; Dos Santos, A.F.; Rodrigues, B.L.; Mosaner,
T.; Lana, J.F. The regenerative mechanisms of platelet-rich plasma: A review. Cytokine 2021, 144, 155560. [CrossRef] [PubMed]
2. Engebretsen, L.; Steffen, K.; Alsousou, J.; Anitua, E.; Bachl, N.; Devilee, R.; Everts, P.; Hamilton, B.; Huard, J.; Jenoure, P.; et al.
IOC consensus paper on the use of platelet-rich plasma in sports medicine. Br. J. Sports Med. 2010, 44, 1072–1081. [CrossRef]
3. Perez, A.G.; Lana, J.F.; Rodrigues, A.A.; Luzo, A.C.; Belangero, W.D.; Santana, M.H. Relevant aspects of centrifugation step in the
preparation of platelet-rich plasma. ISRN Hematol. 2014, 2014, 176060. [CrossRef] [PubMed]
4. Leo, M.S.; Kumar, A.S.; Kirit, R.; Konathan, R.; Sivamani, R.K. Systematic review of the use of platelet-rich plasma in aesthetic
dermatology. J. Cosmet. Dermatol. 2015, 14, 315–323. [CrossRef] [PubMed]
5. Acebes-Huerta, A.; Arias-Fernández, T.; Bernardo, Á.; Muñoz-Turrillas, M.C.; Fernández-Fuertes, J.; Seghatchian, J.; Gutiérrez, L.
Platelet-derived bioproducts: Classification update, applications, concerns and new perspectives. Transfus. Apher. Sci. 2020, 59,
102716. [CrossRef] [PubMed]
6. Sharma, P.; Aurora, J.K.; Dubey, K.N.; Tandon, P.; Tiwari, S. A comparative analysis between intra articular injections of injectable
platelet rich fibrin versus platelet rich plasma in the management of temporomandibular disorders: A randomized control trial.
Natl. J. Maxillofac. Surg. 2023, 14, 249–255. [CrossRef] [PubMed]
7. Lana, J.F.; Purita, J.; Everts, P.A.; De Mendonça Neto, P.A.T.; de Moraes Ferreira Jorge, D.; Mosaner, T.; Huber, S.C.; Azzini, G.O.M.;
da Fonseca, L.F.; Jeyaraman, M.; et al. Platelet-Rich Plasma Power-Mix Gel (ppm)—An Orthobiologic Optimization Protocol Rich
in Growth Factors and Fibrin. Gels 2023, 9, 553. [CrossRef] [PubMed]
8. Emer, J. Platelet-Rich Plasma (PRP): Current Applications in Dermatology. Skin. Therapy Lett. 2019, 24, 1–6.
9. Asim, M.; Shah, R.; Sharif, S.; Ouellette, S.; Shah, A.; Rao, B. A Randomized Control Trial Comparing the Efficacy of Platelet-Rich
Plasma and 5% Topical Minoxidil for the Treatment of Androgenetic Alopecia. J. Drugs Dermatol. 2023, 22, 905–909.
10. Amelia, K.; Hausauer, D.H.J. PRP and Microneedling in Aesthetic Medicine; Georg Thieme Verlag: New York, NY, USA, 2019;
Volume 1.
11. Asilian, A.; Amiri, A.; Mokhtari, F.; Faghihi, G.; Iraji, F.; Mozafarpoor, S. Platelet-rich plasma versus carboxytherapy for the
treatment of periocular hyperpigmentation; which approach is superior? Dermatol. Ther. 2021, 34, e14980. [CrossRef]
12. Cabrera-Ramírez, J.O.; Puebla-Mora, A.G.; González-Ojeda, A.; García-Martínez, D.; Cortés-Lares, J.A.; Márquez-Valdés, A.R.;
Contreras-Hernández, G.I.; Bracamontes-Blanco, J.; Saucedo Ortiz, J.A.; Fuentes-Orozco, C. Platelet-Rich Plasma for the Treatment
of Photodamage of the Skin of the Hands. Actas Dermo-Sifiliográficas 2017, 108, 746–751. [CrossRef]
13. Qu, Q.; Zhou, Y.; Shi, P.; Du, L.; Fan, Z.; Wang, J.; Li, X.; Chen, J.; Zhu, D.; Ye, K.; et al. Platelet-rich plasma for androgenic alopecia:
A randomized, placebo-controlled, double-blind study and combined mice model experiment. J. Cosmet. Dermatol. 2021, 20,
3227–3235. [CrossRef]
14. Gawdat, H.; Allam, R.S.H.M.; Hegazy, R.; Sameh, B.; Ragab, N. Comparison of the efficacy of Fractional Radiofrequency
Microneedling alone and in combination with platelet-rich plasma in neck rejuvenation: A clinical and optical coherence
tomography study. J. Cosmet. Dermatol. 2022, 21, 2038–2045. [CrossRef] [PubMed]
15. Frautschi, R.S.; Hashem, A.M.; Halasa, B.; Cakmakoglu, C.; Zins, J.E. Current Evidence for Clinical Efficacy of Platelet Rich
Plasma in Aesthetic Surgery: A Systematic Review. Aesthet. Surg. J. 2017, 37, 353–362. [CrossRef] [PubMed]
16. Trink, A.; Sorbellini, E.; Bezzola, P.; Rodella, L.; Rezzani, R.; Ramot, Y.; Rinaldi, F. A randomized, double-blind, placebo- and
active-controlled, half-head study to evaluate the effects of platelet-rich plasma on alopecia areata. Br. J. Dermatol. 2013, 169,
690–694. [CrossRef]
17. Vazques, O.A.; Safeek, R.H.; Becker, H. Alopecia Areata Treated with Advanced Platelet-rich Fibrin Using Micronization. Plast.
Reconstr. Surg. Glob. Open 2022, 10, e4032. [CrossRef]
18. Gentile, P.; Garcovich, S.; Bielli, A.; Scioli, M.G.; Orlandi, A.; Cervelli, V. The Effect of Platelet-Rich Plasma in Hair Regrowth: A
Randomized Placebo-Controlled Trial. Stem Cells Transl. Med. 2015, 4, 1317–1323. [CrossRef] [PubMed]
19. Alves, R.; Grimalt, R. Randomized Placebo-Controlled, Double-Blind, Half-Head Study to Assess the Efficacy of Platelet-Rich
Plasma on the Treatment of Androgenetic Alopecia. Dermatol. Surg. 2016, 42, 491–497. [CrossRef]
20. Gentile, P.; Garcovich, S.; Scioli, M.G.; Bielli, A.; Orlandi, A.; Cervelli, V. Mechanical and Controlled PRP Injections in Patients
Affected by Androgenetic Alopecia. J. Vis. Exp. 2018, 131, e56406.
21. Butt, G.; Hussain, I.; Ahmed, F.J.; Choudhery, M.S. Efficacy of platelet-rich plasma in androgenetic alopecia patients. J. Cosmet.
Dermatol. 2019, 18, 996–1001.
Int. J. Mol. Sci. 2024, 25, 5604 22 of 24

22. Rodrigues, B.L.; Montalvão, S.A.L.; Cancela, R.B.B.; Silva, F.A.R.; Urban, A.; Huber, S.C.; Júnior, J.L.R.C.; Lana, J.F.S.D.;
Annichinno-Bizzacchi, J.M. Treatment of male pattern alopecia with platelet-rich plasma: A double-blind controlled study with
analysis of platelet number and growth factor levels. J. Am. Acad. Dermatol. 2019, 80, 694–700. [CrossRef]
23. Shapiro, J.; Ho, A.; Sukhdeo, K.; Yin, L.; Lo Sicco, K. Evaluation of platelet-rich plasma as a treatment for androgenetic alopecia: A
randomized controlled trial. J. Am. Acad. Dermatol. 2020, 83, 1298–1303. [CrossRef]
24. Moftah, N.H.; Taha, N.E.; Alhabibi, A.M.; Hamdino, M. Different platelet-rich plasma preparation protocols in Female pattern
hair loss: Does it affect the outcome? A pilot study. J. Cosmet. Dermatol. 2022, 21, 3316–3326. [CrossRef]
25. Muhammad, A.; Iftikhar, N.; Mashhood, A.; Saleem, Z.; Sundus, M.; Khalid, A.A.; Khan, S.; Naveed, S.; Shahid, W.; Ajmal, U.;
et al. Comparison of Efficacy of Platelet-Rich Plasma (PRP) With PRP Micro needling in Androgenetic Alopecia. Cureus 2022, 14,
e30418. [PubMed]
26. Ozcan, K.N.; Sener, S.; Altunisik, N.; Turkmen, D. Platelet rich plasma application by derma pen micro needling and intradermal
point-by-point injection methods, and their comparison with clinical findings and trichoscan in patients with androgenetic
alopecia. Dermatol. Ther. 2022, 35, e15182. [CrossRef]
27. Wu, S.; Liu, S.; Chen, J.; Dai, D.; Liu, W.; Le, D.; Guan, Q.; Miao, Y.; Hu, Z.; Qu, Q. Evaluation of platelet-rich plasma plus basic
fibroblast growth factor combined with minoxidil in the treatment of androgenetic alopecia: A randomized controlled trial.
J. Cosmet. Dermatol. 2023, 22, 1995–2002. [CrossRef] [PubMed]
28. Wei, W.; Zhang, Y.; Long, B.; Zhang, Y.; Zhang, C.; Zhang, S. Injections of platelet-rich plasma prepared by automatic blood cell
separator combined with topical 5% minoxidil in the treatment of male androgenetic alopecia. Skin Res. Technol. 2023, 29, e13315.
[CrossRef] [PubMed]
29. El-Dawla, R.E.; Abdelhaleem, M.; Abdelhamed, A. Evaluation of the safety and efficacy of platelet-rich plasma in the treatment of
female patients with chronic telogen effluvium: A randomized, controlled, double-blind, pilot clinical trial. Indian J. Dermatol.
Venereol. Leprol. 2023, 89, 195–203. [CrossRef]
30. Elnehrawy, N.Y.; Ibrahim, Z.A.; Eltoukhy, A.M.; Nagy, H.M. Assessment of the efficacy and safety of single platelet-rich plasma
injection on different types and grades of facial wrinkles. J. Cosmet. Dermatol. 2017, 16, 103–111. [CrossRef]
31. Hersant, B.; SidAhmed-Mezi, M.; Niddam, J.; La Padula, S.; Noel, W.; Ezzedine, K.; Rodriguez, A.M.; Meningaud, J.P. Efficacy of
autologous platelet-rich plasma combined with hyaluronic acid on skin facial rejuvenation: A prospective study. J. Am. Acad.
Dermatol. 2017, 77, 584–586. [CrossRef]
32. Alam, M.; Hughart, R.; Champlain, A.; Geisler, A.; Paghdal, K.; Whiting, D.; Hammel, J.A.; Maisel, A.; Rapcan, M.J.; West, D.P.;
et al. Effect of Platelet-Rich Plasma Injection for Rejuvenation of Photoaged Facial Skin: A Randomized Clinical Trial. JAMA
Dermatol. 2018, 154, 1447–1452. [CrossRef]
33. Everts, P.A.; Pinto, P.C.; Girao, L. Autologous pure platelet-rich plasma injections for facial skin rejuvenation: Biometric
instrumental evaluations and patient-reported outcomes to support antiaging effects. J. Cosmet. Dermatol. 2019, 18, 985–995.
[CrossRef]
34. Hassan, H.; Quinlan, D.J.; Ghanem, A. Injectable platelet-rich fibrin for facial rejuvenation: A prospective, single-center study.
J. Cosmet. Dermatol. 2020, 19, 3213–3221. [CrossRef]
35. Cai, J.; Tian, J.; Chen, K.; Cheng, L.H.; Xuan, M.; Cheng, B. Erbium fractional laser irradiation combined with autologous
platelet-rich plasma and platelet-poor plasma application for facial rejuvenation. J. Cosmet. Dermatol. 2020, 19, 1975–1979.
[CrossRef]
36. Hersant, B.; SidAhmed-Mezi, M.; Aboud, C.; Niddam, J.; Levy, S.; Mernier, T.; La Padula, S.; Meningaud, J.P. Synergistic Effects
of Autologous Platelet-Rich Plasma and Hyaluronic Acid Injections on Facial Skin Rejuvenation. Aesthet. Surg. J. 2021, 41,
NP854–NP865. [CrossRef]
37. da Silva, L.Q.; Cancela, R.B.B.; de Lima Montalvão, S.A.; Huber, S.C.; Vieira-Damiani, G.; Triglia, R.M.; Annichino-Bizzacchi, J.M.
The effect of lyophilized platelet rich-plasma on skin aging: A nonrandomized, controlled, pilot trial. Arch. Dermatol. Res. 2021,
313, 863–871. [CrossRef]
38. Banihashemi, M.; Zabolinejad, N.; Salehi, M.; Hamidi Alamdari, D.; Nakhaizadeh, S. Platelet-rich Plasma use for facial rejuvena-
tion: A clinical trial and review of current literature. Acta Biomed. 2021, 92, e2021187.
39. Nilforoushzadeh, M.A.; Heidari-Kharaji, M.; Alavi, S.; Mahmoudbeyk, M.; Torkamaniha, E.; Peyrovan, A.; Nouri, M.; Zare, S.
Assessing the effectiveness of the combination therapy with fractional Er-YAG laser and platelet-rich plasma in treatment of
periorbital dark circles patients: A clinical trial. J. Cosmet. Dermatol. 2021, 20, 3526–3536. [CrossRef]
40. Mumtaz, M.; Chandio, T.H.; Shahzad, M.K.; Hanif, N.; Anwar, S.; Rafique, S. Comparing the Efficacy of Patelet-rich Plasma (PRP)
versus Tranexamic Acid (4 mg/mL) as Intradermal Treatments of Melasma. J. Coll. Physicians Surg. Pak. 2021, 30, 502–505.
41. Elfar, N.N.; Hasby, E.A. Efficacy and safety of plasma gel versus platelet-rich plasma in periorbital rejuvenation: A comparative
split-face clinical and Antera 3D camera study. Arch. Dermatol. Res. 2022, 314, 661–671.
42. Patil, N.K.; Bubna, A.K. A comparative evaluation of the efficacy of intralesional tranexamic acid versus platelet rich plasma in
the treatment of melasma. Dermatol. Ther. 2022, 35, e15534. [CrossRef]
43. González-Ojeda, A.; Cervantes-Guevara, G.; Chejfec-Ciociano, J.M.; Cervantes-Cardona, G.A.; Acevedo-Guzman, D.; Puebla-
Mora, A.G.; Cortés-Lares, J.A.; Chávez-Tostado, M.; Álvarez-Villaseñor, A.S.; Cervantes-Pérez, E.; et al. Treatment of melasma
with platelet-rich plasma: A self-controlled clinical trial. Dermatol. Ther. 2022, 35, e15703. [CrossRef]
Int. J. Mol. Sci. 2024, 25, 5604 23 of 24

44. Shen, J.; Yu, X.; Zhuang, Y.; Kong, Y.; Zhao, J.; Yao, Z. Clinical efficacy and safety of targeted injection of PRP with skin booster in
the treatment of aging face. Biotechnol. Genet. Eng. Rev. 2023, 1–17. [CrossRef]
45. Mahmoodabadi, R.A.; Golafshan, H.A.; Pezeshkian, F.; Shahriarirad, R.; Namazi, M.R. Evaluation of the Effect of Platelet-Rich
Fibrin Matrix in the Correction of Periorbital Wrinkles: An Experimental Clinical Trial. Dermatol. Pract. Concept. 2023, 13, e2023050.
[CrossRef]
46. Asif, M.; Kanodia, S.; Singh, K. Combined autologous platelet-rich plasma with micro needling verses micro needling with
distilled water in the treatment of atrophic acne scars: A concurrent split-face study. J. Cosmet. Dermatol. 2016, 15, 434–443.
[CrossRef]
47. Deshmukh, N.S.; Belgaumkar, V.A. Platelet-Rich Plasma Augments Subcision in Atrophic Acne Scars: A Split-Face Comparative
Study. Dermatol. Surg. 2019, 45, 90–98. [CrossRef]
48. Krishnegowda, R.; Pradhan, S.N.; Belgaumkar, V.A. A Split-Face Study to Evaluate Efficacy of Autologous Injectable Platelet-Rich
Fibrin with Microneedling Against Microneedling with Normal Saline (Placebo Control) in Atrophic Acne Scars. Dermatol. Surg.
2023, 49, 938–942. [CrossRef]
49. Diab, N.A.F.; Ibrahim, A.M.; Abdallah, A.M. Fluid Platelet-Rich Fibrin (PRF) versus Platelet-Rich Plasma (PRP) in the Treatment
of Atrophic Acne Scars: A Comparative Study. Arch. Dermatol. Res. 2023, 315, 1249–1255. [CrossRef]
50. Guo, R.; Xuan, W.; He, X.; Xu, K. Safety and efficacy of CO2 dot matrix laser combined with platelet-rich plasma on depressed
scar after acne vulgaris and influencing factors of its repair effect: A retrospective analysis. J. Cosmet. Dermatol. 2023, 22, 850–861.
[CrossRef]
51. Neinaa, Y.M.E.; Gheida, S.F.; Mohamed, D.A.E. Synergistic effect of platelet-rich plasma in combination with fractional carbon
dioxide laser versus its combination with pulsed dye laser in striae distensae: A comparative study. Photodermatol. Photoimmunol.
Photomed. 2021, 37, 214–223. [CrossRef]
52. Preclaro, I.A.C.; Tianco, E.A.V.; Buenviaje-Beloso, M. Efficacy of ablative fractional carbon dioxide laser combined with autologous
platelet-rich plasma versus ablative fractional carbon dioxide laser and placebo in the treatment of striae gravidarum: A
randomized clinical trial. J. Cosmet. Dermatol. 2022, 21, 4354–4364. [CrossRef]
53. Abdel-Motaleb, A.A.; Zedan, H.; Mostafa, M.M.; Abu-Dief, E.E.; Gebril, S.M.; Abdelwahed Hussein, M.R. Combined mi-
cro needling with topical application of platelet-rich plasma versus micro needling alone in the treatment of stria distensae:
Clinicopathological analysis. J. Dermatol. Treat. 2022, 33, 836–847. [CrossRef]
54. Ebrahim, H.M.; Salem, A.; Salah, T.; Eldesoky, F.; Morsi, H.M. Subcision, chemical peels, and platelet-rich plasma: Combination
approaches for the treatment of striae distensae. Dermatol. Ther. 2022, 35, e15245. [CrossRef]
55. de Castro Roston, J.R.; Reis, I.B.; Luzo, Â.C.M.; Roston, M.O.; Durán, N.; Fávaro, W.J. Evaluation of the tissue repair process and
immunomodulatory action of Platelet-Rich Plasma (PRP) in the treatment of abdominal stretch marks. Tissue Cell 2023, 83, 102132.
[CrossRef]
56. Sayed, D.S.; Badary, D.M.; Ali, R.A.; Abou-Taleb, D.A.E. Combined Fractional CO2 Laser with Intradermal Platelet-Rich Plasma
versus Fractional CO2 Laser Alone in the Treatment of Striae Distensae. Dermatol. Surg. 2023, 49, 552–558. [CrossRef]
57. Panchaprateep, R. Medical Treatment for Androgenetic Alopecia. Facial Plast. Surg. 2023, 40, 252–266. [CrossRef]
58. Paichitrojjana, A.; Paichitrojjana, A. Platelet Rich Plasma and Its Use in Hair Regrowth: A Review. Drug Des. Dev. Ther. 2022, 16,
635–645. [CrossRef]
59. Gupta, A.K.; Renaud, H.J.; Bamimore, M. Platelet-rich plasma for androgenetic alopecia: Efficacy differences between men and
women. Dermatol. Ther. 2020, 33, e14143. [CrossRef]
60. Beltrán, B.; Sánchez, M.A.R.; Melamed, G.; Pinto, H. Efficacy and safety of photothermal-bioactivated platelet-rich plasma for
facial rejuvenation. J. Cosmet. Dermatol. 2023, 22, 671–673. [CrossRef]
61. Xiao, H.; Xu, D.; Mao, R.; Xiao, M.; Fang, Y.; Liu, Y. Platelet-Rich Plasma in Facial Rejuvenation: A Systematic Appraisal of the
Available Clinical Evidence. Clin. Cosmet. Investig. Dermatol. 2021, 14, 1697–1724. [CrossRef]
62. Atsu, N.; Ekinci-Aslanoglu, C.; Kantarci-Demirkiran, B.; Caf, N.; Nuhoglu, F. The Comparison of Platelet-Rich Plasma versus
Injectable Platelet Rich Fibrin in Facial Skin Rejuvenation. Dermatol. Ther. 2023, 2023, 3096698. [CrossRef]
63. Popescu, M.N.; Iliescu, M.G.; Beiu, C.; Popa, L.G.; Mihai, M.M.; Berteanu, M.; Ionescu, A.M. Autologous Platelet-Rich Plasma
Efficacy in the Field of Regenerative Medicine: Product and Quality Control. Biomed. Res. Int. 2021, 2021, 4672959. [CrossRef]
64. Lee, Z.H.; Sinno, S.; Poudrier, G.; Motosko, C.C.; Chiodo, M.; Saia, W.; Gothard, D.; Thomson, J.E.; Hazen, A. Platelet rich plasma
for photodamaged skin: A pilot study. J. Cosmet. Dermatol. 2019, 18, 77–83. [CrossRef]
65. Shin, M.K.; Lee, J.H.; Lee, S.J.; Kim, N.I. Platelet-rich plasma combined with fractional laser therapy for skin rejuvenation.
Dermatol. Surg. 2012, 38, 623–630. [CrossRef]
66. Bhatt, M.; Jamale, V.; Kale, M.; Hussain, A.A.; Nikam, B.P. Monotherapy of Biofiller for Atrophic Acne Scars: A Prospective
Nonrandomized Study. J. Cutan. Aesthet. Surg. 2022, 15, 260–266.
67. Cho, E.B.; Park, G.S.; Park, S.S.; Jang, Y.J.; Kim, K.H.; Kim, K.J.; Park, E.J. Effect of platelet-rich plasma on proliferation and
migration in human dermal fibroblasts. J. Cosmet. Dermatol. 2019, 18, 1105–1112. [CrossRef]
68. Zhang, D.D.; Zhao, W.Y.; Fang, Q.Q.; Wang, Z.C.; Wang, X.F.; Zhang, M.X.; Hu, Y.Y.; Zheng, B.; Tan, W.Q. The efficacy of fractional
CO2 laser in acne scar treatment: A meta-analysis. Dermatol. Ther. 2021, 34, e14539. [CrossRef]
Int. J. Mol. Sci. 2024, 25, 5604 24 of 24

69. Sawetz, I.; Lebo, P.B.; Nischwitz, S.P.; Winter, R.; Schaunig, C.; Brinskelle, P.; Kamolz, L.P.; Gualdi, A.; Lumenta, D.B. Platelet-rich
plasma for striae distensae: What do we know about processed autologous blood contents for treating skin stretchmarks?—A
systematic review. Int. Wound J. 2021, 18, 387–395. [CrossRef]
70. Sany, I.; Mohamed Sobhi, R.; Badawi, A.; Mohamed Elmaadawi, Z.; Mostafa PI, N. Comparative Study between the Efficacy of
Fractional CO2 Laser/Radiofrequency, PRP and a Combination of Both in the Treatment of Striae Distensae: A Pilot Study. Clin.
Cosmet. Investig. Dermatol. 2022, 15, 1687–1694. [CrossRef]
71. La Padula, S.; Hersant, B.; Pizza, C.; Chesné, C.; Jamin, A.; Ben Mosbah, I.; Errico, C.; D’Andrea, F.; Rega, U.; Persichetti, P.; et al.
Striae Distensae: In Vitro Study and Assessment of a Combined Treatment with Sodium Ascorbate and Platelet Rich Plasma on
Fibroblasts. Aesthetic Plast. Surg. 2022, 46, 561–562. [CrossRef]
72. Wang, X.; Yang, Y.; Zhang, Y.; Miron, R.J. Fluid Platelet-Rich Fibrin Stimulates Greater Dermal Skin Fibroblast Cell Migration,
Proliferation, and Collagen Synthesis When Compared to Platelet-Rich Plasma. J. Cosmet. Dermatol. 2019, 18, 2004–2010.
[CrossRef] [PubMed]

Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual
author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to
people or property resulting from any ideas, methods, instructions or products referred to in the content.