Journal of Cosmetic and Laser Therapy

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A prospective study comparing topic platelet-rich

plasma vs. placebo on reducing superficial perioral
wrinkles and restore dermal matrix

Antonino Araco

To cite this article: Antonino Araco (2019): A prospective study comparing topic platelet-rich
plasma vs. placebo on reducing superficial perioral wrinkles and restore dermal matrix, Journal of
Cosmetic and Laser Therapy, DOI: 10.1080/14764172.2019.1605448

To link to this article: https://doi.org/10.1080/14764172.2019.1605448

Published online: 07 May 2019.

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JOURNAL OF COSMETIC AND LASER THERAPY
https://doi.org/10.1080/14764172.2019.1605448

A prospective study comparing topic platelet-rich plasma vs. placebo on reducing

superficial perioral wrinkles and restore dermal matrix
Antonino Araco
Cosmetic Surgeon at Villa Salaria, private hospital, Rome, Italy

ABSTRACT ARTICLE HISTORY

Introduction: The goal of our prospective study was to assess the efficacy of the topical Platelet-rich plasma Received 12 December 2017
on reducing superficial perioral wrinkles and restoring the dermal matrix. Revised 11 August 2018
Materials and methods: 50 women with moderate to severe perioral wrinkles were treated on the Accepted 5 April 2019
perioral area by a single session of fractional CO2 laser skin resurfacing plus intradermal injection of prp. KEYWORDS
25 patients (group 1) applied topically prp twice a day for 12 weeks as post laser treatment. 25 (group 2) Growth factors; regenerative
applied gentamicin and betamethasone twice a day for the first 7 days and then hyaluronic acid gel for medicine; face wrinkles;
the following 12 weeks. perioral wrinkles; dermal
Results: In group 1, moisture (p < 0.001), amount of collagen fiber (p < 0.001) skin elasticity (p < 0.001), matrix
PSAl (p < 0.001) and SSAl (p < 0.001) improved significantly. In group 2 all the parameters investigated
improved but did not reach significant difference.
Discussion: Our medical device with a plasma-like formulation is able to maintain prp active for a period
of 7 days so patients are able to apply topically growth factors at home.
Conclusions: Our prospective study proves that the use of topical prp reduces superficial perioral
wrinkles and restore dermal matrix when used at home for 12 weeks.

Introduction So far there is not an international consensus on their

clinical use in esthetic medicine because of a lack of rando-
Face wrinkles and depressed areas represents visible signs of
mized scientific studies about their clinical efficacy (31,32)
face aging (1) and they are the major cosmetic concerns for
The goal of our prospective study was to assess the efficacy
men and women.
of the Prp on reducing superficial perioral wrinkles (lifting
The causes of its formations are multifactorial: genetic (2),
effect) and restoring the dermal matrix.
environmental i.e. pollution (3) and chronic sun exposure
For this purpose, in collaboration with the department of
(4–6), personal factors such as ethnicity (7), stress and cigar-
pharmacy and applied biotechnology of the University of
ette smoking (8–10).
Perugia (Italy), we developed and patented a thermosensitive
The mechanism of wrinkles formation appears to involve:
gel formulation (Medical Device) able to embed Prp and
qualitative and quantitative changes on the dermis and extra-
growth factors for topic application.
cellular matrix components (11); free radicals cellular damages
This Medical Device has the ability to stay in a liquid status
and impaired dermal blood vessels (12); an increase of the static
when the temperature is below 20°C and this allows the
contraction of the facial muscles due to aging and stress (13).
mixing with the Prp.
Facial wrinkles are divided into superficial and deep: the
Once the temperature exceeds 35 C° (for example, when
superficial wrinkles are caused mainly by facial movements
the liquid medical device added with Prp touch the skin), the
(also called expression lines) and are visible on the forehead,
liquid state becomes a gel, and this let the growth factors to be
glabella, lateral eyes (crow’s feet) and mouth. They are generally
absorbed by the dermis.
treated with fillers (14–16) and toxin botulin injections (17–19).
Our researches on the medical devise showed that platelets and
Deep wrinkles are associated with advanced aging and/or
growth factors can be stored on it and remain fully active for
weight loss and are visible to naso-labia folds, neck and jowls.
7 days.
They generally require surgery (20,21).
Platelet-rich plasma (Prp) contains growth factors that
have proved to accelerate healing process in many fields of Materials and methods
medicine (22–25). The study was conducted in accordance with the ethical
Studies have showed promising results in reconstructive principles that have their origin in the 1975 Declaration of
surgery for the treatment of ulcers (26,27) and burns (28) as Helsinki and are consistent with the Good Clinical Practice
well as in esthetic medicine and dermatology (29,30). principles.

CONTACT Antonino Araco aracoantonino@gmail.com Piazza Dei Re di Roma 71, Roma 00183, Italy
© 2019 Taylor & Francis Group, LLC
2 A. ARACO

Table 1. Facial wrinkle scale. Eight ml pf Prp is mixed with 8 ml of medical device and
Facial wrinkle scale gently shacked for 3 minutes in order to guarantee the opti-
None 0 mal distribution.
Mild 1
Moderate 2
Severe 3
Techniques of application
Patients were previously treated on the perioral area by
Study population a single session of fractional CO2 laser skin resurfacing
(Deka Laser) in order to expose the dermal-epidermal
Eligible study participants were 50 women with moderate to
junction.
severe perioral wrinkles on a four-point facial wrinkle scale
Twenty-five patients (group 1) applied 5 drops of topical
(FWS) (Table 1) admitted at the private cosmetic medicine
Prp stored inside the medical device twice a day for 12 weeks
center of Rome over a 6 months period.
as post laser treatment.
Patients were informed about the protocol, signed a consent
Twenty-five patients (group 2) applied gentamicin and
form and before the treatment they were asked to suspend the
betamethasone twice a day for the first 7 days and then
use of cosmetic creams for at least 4 weeks and avoid exposure
hyaluronic acid gel for the following 12 weeks.
to sun or UV rays and intensive sport activities.
Exclusion criteria were the presence of pre-existing local
skin diseases, use of topical or systemic steroids and treatment Assessment of efficacy and tolerability
with intradermal hyaluronic acid, botulin toxin or any other
Patients were previously analyzed for photo type, hydration,
laser treatments in the last 6 months.
collagen fiber content and elasticity using the digital skin
analyzer (CBS 1800, WUHAN BOSEVIEW ELECTRONIC
Preparation of Prp CO. Sincoheren Science and technology developing Cp., Ltd)
(Table 2).
For the preparation of the Prp we used the Plasma Active Digital macro-photographs were provided (Nikon D7100,
system (CE0373 – Medical Device s.r.l. via artigianato n.6, 12.0 megapixels, AF-5 micro nikkor 60 mm, close-up 4D –
52022 Meleto, Craviglia (AR) – Italy). 62 mm), to ensure reproducibility in terms of positioning and
It is composed on two vacutainer tubes (BD Vacutainer® lighting.
Brand SST II) of 9 mm each with separator gel and anti- The automatic camera control provided professional illu-
coagulant for harvesting 18 ml of peripheral blood. mination by spreading the flashlight in order to avoid sha-
The tubes were centrifugated for 5 minutes at 1800 rpm dows or reflections on the skin by Nital Macro Lighting
(Sorvall Legend XTR Centrifuge – Thermo Fisher Scientific Spider.
Robert-Bosch-Straße 1 D – 63505 Langenselbold Germany) Two independent doctors (FA and MA) individually
and 8 ml of Prp were collected from the upper part of the assessed the wrinkle reduction with the FWS and the lifting
tube in a sterile matter and placed inside the Medical Device. effect by the SSAl scale (Surgeon satisfaction assessment
lifting).
Patients were given a self-assessment scale (PSAl – Patient
Preparation of medical device with Prp
satisfaction assessment lifting) (Table 3).
We set up a count system in order to characterize platelets Efficacy and tolerability of the treatment were assessed at 6
and developed an accurate HPLC procedure for epidermal and 12 weeks and 6 months of treatment.
growth factor (EGF) quantification of the Prp contained on The primary efficacy end point was the skin quality
the Medical device. assessed by the “Intelligent skin analyzer” on both groups at
Furthermore, we set up and characterize a series of poloxamer 12 weeks.
formulations suitable to embed Prp and other growth factors. The second efficacy end point was the wrinkles reduction
After a detailed research on the scientific literature (33,34) and the lifting effect assessed by the panel of two doctors and
poloxamer 407 was chosen to prepare thermosensitive formu-
lation to embed and deliver Prp and growth factors.
Table 2. Digital skin analyser.
Multiple reasons have corroborated this choice.
Digital skin analyzer
First of all, the family of “poloxamer” polymers is listed in
Idratation
the US and European Pharmacopoeia (35) and is approved by Dry skin 0–3%
FDA for parenteral use in humans. Ageing skin 4–10%
Normal water content 10–15%
This ensure safety, biocompatibility and tolerability High water content >15%
required also for topic use. Collagen fiber
Furthermore, poloxamer 407, being a non-ionic block Normal collagen content 60–85%
Reduced collagen content 50–60%
copolymer, should not negatively interact with the biomole- Deep reduction 40–50%
cules to embed in the gel, such as platelets or growth factors Serious lack <40
Elasticity
and finally it allows to develop thermosensitive formulations Normal skin elasticity 50–60%
without the need to add a lot of excipients in prepara- Weak skin 35–50%
tions (35). Loose skin 15–35%
 JOURNAL OF COSMETIC AND LASER THERAPY 3

Table 3. SSAl and PSAl assessment. Table 5. Clinical result.

SSAl Clinical result n = 50
(surgeon satisfaction assessment on skin lifting) GROUP 1 BEFORE 12 weeks AFTER
Very poor 2 Moisture 5,8 (0,7) 14,3 (1,22) <0.001
Poor 4 Collagen fiber 38 (5) 64 (1,5) <0.001
Acceptable 6 Elasticity 32,6 (3,5) 46,2 (3) <0.001
Good 8 GROUP 2 BEFORE 12 weeks AFTER
Excellent 10 Moisture 5,3 (1,2) 6,2 (1) NS
PSAl Collagen fiber 42 (3,4) 54 (0,8) NS
(patient satisfaction assessment skin lifting) Elasticity 34,2 (2,3) 49,6 (2,5) NS
Very poor 2 GROUP 1 BEFORE 12 weeks AFTER
Poor 4 PSAl 3,88 (0,75) 8,2 (1,0) <0.001
Acceptable 6 SSAl 2,88 (1,5) 6 (1,4) <0.001
Good 8 GROUP 2 BEFORE 12 weeks AFTER
Excellent 10 PSAl 4,2 (0,3) 6,2 (0,4) NS
SSAl 3,1 (1) 5,6 (1,2) NS

by patients from standardized digital photographs according

to the SSAl and PSAl. The superficial wrinkles in group 1 improved significantly
Patient with an improvement of at least one point in global according to PSAl (3.88 vs. 8.2, p < .001) and SSAl (2.88 vs. 6.;
assessment were classified as “responders”. p < .001) at 12 weeks (Table 5).
Result in group 2.
Moisture (5.3% vs. 6,2%; p:NS), amount of collagen fibers
(42% vs. 54%; p:NS), skin elasticity (34,2% vs. 49,6%; p:NS),
Statistical analysis PSAl (4,2 vs. 6,2 p:NS) and SSAl (3,1 vs. 5,6 p:NS) improved
The analysis of data was performed using the Statistical but did not reach significant difference (Table 5).
Package for the Social Sciences Windows version 13.0 (SPSS,
Chicago, IL, USA).
Descriptive statistics for quantitative continuous variables
Discussion
were the mean and standard deviation after confirmation of
normal distribution. Our prospective study focused on the treatment of superficial
Normality assumptions have been demonstrated with his- perioral wrinkles.
tograms, Q–Q plots, Skewness and Kurtosis, Kolmogorov/ Those wrinkles appears around the mouths mostly on the
Smirnov and Shapiro Wilk testings. upper side as vertical superficial lines.
Descriptive statistics for qualitative categorical variables Current treatment involves different commercial products,
was performed with frequencies. such hyaluronic acid (36,37), calcium hydroxylapatite (38,39),
Student’s test was used to compare continuous variables poly-L-lactic acid (40,41).
among groups. χ2 test and Fisher‘s exact test were used to Those products vary on properties of longevity, potentiality
compare nominal variables. for causing allergic reaction, safety, indication, and physicians
All p-values were considered significant if inferior to 0.05. can select the most suitable agent for each patient by con-
sidering the advantage and disadvantage.
Although fillers have lower immunogenicity and can
induce low incidence of allergic reaction, to be appropriate
Results for biomedical use, they must be non-movable, and they
From October 2016 to February 2017, 50 women were should take longer time for resorption.
enrolled for the study and all received full treatment and In the literature, there are several articles showing side
completed follow-up at 12 weeks. effect from filler (42) as allergic reaction (43) inflammatory
Demographic characteristics and clinical results are sum- nodule formation (44), infection, purpura (45), vision loss
marized in Table 4. (46) and its use is limited in human immunodeficiency (47).
No side effects were reported during the study. Plasma-rich growth factors have proved to achieve regen-
Result in group 1. erative capacity on human tissues (48) and positive effect on
Moisture (5.8% vs. 14,3%; p < .001), amount of collagen facial dermal fibroblasts (49,50).
fibers (38% vs. 64%; p < .001) and skin elasticity (32,6% vs. Furthermore, accelerate the healing process in facial reju-
46,2%; p < .001) improved significantly according to the venation when combined with fractional laser (51,52) and
intelligent skin analyzer at 12 weeks of treatment. micro needling (53).
Autologous plasma filler was first introduced by Krajcik
et al. in 1999 and according to the found results, they could
Table 4. Demographic.
identify the autologous plasma filler injection site even after
Demographic n = 50
550 days.
Age (years) 51,6 ± 8,3
Sex (males) 5 (9.8%) Also, they showed that it maintained a good response when
Phototype 3,5 ± 0,3 it was injected into the wrinkles at 3 to 6 months interval, for
BMI 24,1 ± 0,8
2 years, 0.05–0.1 cc in deep wrinkles at 5–10 mm distance and
4 A. ARACO

0.02–0.05 cc in shallow wrinkles at 3 mm distance. There was

no significant side effect (54).
Young Jun Choi presented a clinical study on the useful-
ness of autologous plasma filler in the treatment of nasolabial
fold wrinkles.
In this study, there was 47.1% improvement in wrinkles after
1 week of treatment, and also there was maintenance of improve-
ment in wrinkles at 39.2% after 4 weeks, 21.6% after 8 weeks, and
15.7% after 12 weeks in the physician’s objective assessment and all
these values were statistically significant (p < .01) (55).
Again, N. Elnehrawy, assessed the efficacy and safety of single
Prp injection on different types and grades of facial wrinkles.
He concluded that single treatment with autologous PRP is
well tolerated and can produce a significant correction of wrin-
kles, without development of excessive fibrosis, injection of for-
eign substance, or need for downtime and PRP treatment has
statistically significant result on skin homogeneity and texture.
Those studies were done by needle dermal injection of Prp
and for the best of our knowledge there is not a single clinical
study testing the efficacy of topic Prp in cosmetic medicine Figure 1. 62 y.o. women with perioral wrinkles.
and dermatology.
Among scientific literature there is not a large clinical series
to assess the real efficacy of the Prp not a meta-analysis study.
So, there are at least three main problems in testing the
clinical efficacy of topic Prp in clinical trials: the first is the
lack of a unique preparation and execution protocol (56–58);
the second is the variability of the clinical administration that
can vary from 1 session per week to one session every months,
and also one single administration (59,60).
Furthermore, the fast reduction of the concentration of the
growth factors on target side below the therapeutic level,
make the treatment variable.
So, in order to maintain high the concentration of platelet
growth factors at the target side, our patients applied topic
Prp on skin every day.
Those was possible thanks to our new developed Medical
Device, able to store and maintain active platelets and growth
factors for an average of 7 days.
In fact, once a week, patients came to our medical office for
the preparation of the Prp and the mixing with the Medical
Device and they were just asked to put some drops of the
liquid on the skin at home.
When the Prp mixed on the medical device touches the sur-
Figure 2. 62 y.o. women after 12 weeks of Prp treatment.
face of the skin, where the temperature is above 35°, it becomes
a gel and let the growth factors to be absorbed by the dermis.
In our prospective study, we aimed to prove the clinical The use of our developed Medical Device is crucial; in fact,
effectiveness of topic Prp on reducing superficial perioral platelets and growth factors have a very short live when outside
wrinkles and restore dermal matrix. the plasma; so that they must be put in a system that reproduce
For this purpose, we previously treated patients with a Co2 an ideal environment for them and make them more stable.
laser in order to reduce the epidermal barrier and let a simpler We believe that our clinical result can be further investigated
absorption of the growth factors. through prospective and randomized clinical trials in cosmetic
Our clinical results were very encouraging as shown in medicine and for the treatment of ulcers and hard-to-heal wounds.
Figures 1–4.
Patients treated with topic Prp showed a significative dif-
ference on all the parameters assessed (moisture, amount of
Conclusions
collagen fiber, skin elasticity, PSAl and SSAl) compared to
patients treated with conservative medications. Our prospective study proves that the use of topical Prp reduces
This confirm the regenerative capacity of Prp and prove superficial perioral wrinkles and restore dermal matrix when
that topic treatment can be effective. used topically at home for a period of at least 12 weeks.

References
Figure 3. 62 y.o. women after 6 monthe of Prp treatment.
Figure 4. 60 y.o. women with perioral wrinkles.
For this purpose, it is necessary the use of a medical device
able to preserve growth factors in ideal conditions and make
them bioavailable for home-based use.
We believe that further prospective and randomized study
are necessary to prove of efficacy of topical Prp in cosmetic
medicine and reconstructive surgery.
Disclosure statement
To the Editor of Journal of Cosmetic and Laser Therapy Journal.
With the present I state that I have no conflicts of interest in the
present study.
I have received no funds and I have not paid and unpaid relationships
with any industry manufacturers, publishers, or other companies.
Dott. Antonino Araco
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