10.5826/dpc.1301a50
Introduction: Skin rejuvenation techniques have gained substantial popularity due to increased life expectancy over recent years. Platelet-rich fibrin matrix (PRFM) is the new generation of platelet aggregate products that have surfaced in recent years to treat skin aging.
Objectives: We intend to use PRF to correct periorbital wrinkles in 15 volunteers and evaluate its effectiveness in this study.
Methods: To evaluate the efficacy of PRFM intervention, eight men and women over the age of thirty entered our study. Blood samples were taken and were immediately centrifuged at 700rpm for 5 minutes. PRFM was extracted from the plasma and was injected at the sub-dermis site in periorbital areas. The initial severity of periorbital wrinkles was determined by Visioface 1000D, and obtained numbers were delivered to the statistical unit for statistical analysis. Scoring and evaluation were based on tissue volume and depth and were measured before and twelve weeks after injection. Adverse effects were also taken into consideration. 
Results: The results demonstrated noticeable improvement in deep, fine, and small wrinkles, periocular hyperpigmentation, and overall skin freshness of the injection site. The subjects had swelling in the injection site for up to one day after the injection, which resolved without complications.
Conclusions: PRFM was observed to have potential in skin rejuvenation, demonstrating promising outcomes in terms of safety and long-term effects in improving skin condition.
text/xml
2160-9381
2535
en
Mohammad Reza  Namazi
https://creativecommons.org/licenses/by-nc/4.0
Dermatology Practical & Conceptual
Cosmetics
Evaluation of the Effect of Platelet Rich Fibrin Matrix in the Correction of Periorbital Wrinkles: An Experimental Clinical Trial
Text.Serial.Journal
https://dpcj.org/index.php/dpc
Original Article
2023-01-31
2022-04-12
2023-01-31
2023-08-21
e2023050
Dermatol Pract Concept
Introduction: Skin rejuvenation techniques have gained substantial popularity due to increased life expectancy over recent years. Platelet-rich fibrin matrix (PRFM) is the new generation of platelet aggregate products that have surfaced in recent years to treat skin aging.
Objectives: We intend to use PRF to correct periorbital wrinkles in 15 volunteers and evaluate its effectiveness in this study.
Methods: To evaluate the efficacy of PRFM intervention, eight men and women over the age of thirty entered our study. Blood samples were taken and were immediately centrifuged at 700rpm for 5 minutes. PRFM was extracted from the plasma and was injected at the sub-dermis site in periorbital areas. The initial severity of periorbital wrinkles was determined by Visioface 1000D, and obtained numbers were delivered to the statistical unit for statistical analysis. Scoring and evaluation were based on tissue volume and depth and were measured before and twelve weeks after injection. Adverse effects were also taken into consideration. 
Results: The results demonstrated noticeable improvement in deep, fine, and small wrinkles, periocular hyperpigmentation, and overall skin freshness of the injection site. The subjects had swelling in the injection site for up to one day after the injection, which resolved without complications.
Conclusions: PRFM was observed to have potential in skin rejuvenation, demonstrating promising outcomes in terms of safety and long-term effects in improving skin condition.
Mohammad Reza  Namazi
2023/01/31
10.5826/dpc.1301a50
e2023050
Molecular Dermatology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
2160-9381
Cosmetics
en
e2023050
Nacopoulos C, Vesala A-M. Lower facial regeneration with a combination of platelet-rich fibrin liquid matrices based on the low speed centrifugation concept-Cleopatra technique. Journal of Cosmetic Dermatology. 2020;19(1):185-189.
Evaluation of the Effect of Platelet Rich Fibrin Matrix in the Correction of Periorbital Wrinkles: An Experimental Clinical Trial
https://dpcj.org/index.php/dpc/article/download/2535/1977
     Evaluation of the Effect of Platelet-Rich Fibrin
     Matrix in the Correction of Periorbital Wrinkles:
              An Experimental Clinical Trial
     Razieh Ahmadi Mahmoodabadi 1, Habib Allah Golafshan2, Fatemehsadat Pezeshkian3,
                     Reza Shahriarirad4, Mohammad Reza Namazi5


1 Department of Dermatology, Shiraz University of Medical Sciences, Shiraz, Iran
2 Shiraz Paramedical School, Shiraz University of Medical Sciences, Shiraz, Iran
3 Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran
4 School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
5 Molecular Dermatology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran



Key words: platelet-rich fibrin matrix, skin, cosmetics
Citation: Ahmadi Mahmoodabadi R, Golafshan AH, Pezeshkian F, Shahriarirad R, Namazi M. Evaluation of the Effect of Platelet Rich
Fibrin Matrix in the Correction of Periorbital Wrinkles: An Experimental Clinical Trial. Dermatol Pract Concept. 2023;13(1):e2023050.
DOI: https://doi.org/10.5826/dpc.1301a50
Accepted: August 23, 2022; Published: January 2023
Copyright: ©2023 Ahmadi Mahmoodabadi et al. This is an open-access article distributed under the terms of the Creative Commons
Attribution-NonCommercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted
noncommercial use, distribution, and reproduction in any medium, provided the original authors and source are credited.
Funding: None.
Competing Interests: None.
Authorship: All authors have contributed significantly to this publication.
Corresponding Author: Mohammadreza Namazi; Molecular Dermatology Research Center, Shiraz University of Medical Sciences,
Shiraz, Iran; E-mail: Namazi_mr@yahoo.com




  ABSTRACT              Introduction: Skin rejuvenation techniques have gained substantial popularity due to increased life
                        expectancy over recent years. Platelet-rich fibrin matrix (PRFM) is the new generation of platelet ag-
                        gregate products that have surfaced in recent years to treat skin aging.
                        Objectives: We intend to use PRF to correct periorbital wrinkles in 15 volunteers and evaluate its
                        effectiveness in this study.
                        Methods: To evaluate the efficacy of PRFM intervention, eight men and women over the age of thirty
                        entered our study. Blood samples were taken and were immediately centrifuged at 700rpm for 5 minutes.
                        PRFM was extracted from the plasma and injected at the sub-dermis site in periorbital areas. The initial
                        ­severity of periorbital wrinkles was determined by Visioface 1000D, and obtained data were delivered to
                         the statistical unit for statistical analysis. Scoring and evaluation were based on tissue volume and depth and
                         were measured before and twelve weeks after injection. Adverse effects were also taken into consideration.
                        Results: The results demonstrated noticeable improvement in deep, fine, and small wrinkles, periocu-
                        lar hyperpigmentation, and overall skin freshness of the injection site. The subjects had swelling in the
                        injection site for up to one day after the injection, which resolved without complications.
                        Conclusions: PRFM was observed to have potential in skin rejuvenation, demonstrating promising
                        outcomes in terms of safety and long-term effects in improving skin condition.




Original Article | Dermatol Pract Concept. 2023;13(1):e2023050                                                                             1
Introduction                                                      the injection site [9]. This study intends to use PRF to cor-
                                                                  rect periorbital wrinkles in 15 volunteers and evaluate its
Throughout the years, concerns regarding skin aging have          effectiveness.
increased substantially, even affecting the young generations
due to increased life expectancy [1]. The dermis, the inner
                                                                  Methods
layer of skin, which mainly consists of collagen and elas-
tin, has the role of forming skin structure. The aging pro-       Study Design and Participants
cess destructs the elasticity of these fibers and reduces the     In this prospective clinical trial, sixteen adult women and
production of hyaluronic acid; thus, skin aging results from      men over the 30-year-old with facial wrinkles who volun-
a lack of elasticity, collagen bundle fragility, and fragmenta-   teered to participate were included in the study. Participants
tion [2, 3]. Alongside intrinsic factors, environmental factors   were excluded in cases younger than 30 years old, signifi-
such as chemical exposure, ultraviolet radiation, smoking,        cant past medical history, such as connective tissue disor-
and psychological changes also play a noticeable part in the      der, myocardial infarction, hypertension, pregnancy, and
aging process [3, 4]. Some studies have discussed the possi-      use of immunomodulatory or anticoagulation (e.g., Aspirin,
ble role of reactive oxygen species (ROS) in leading the skin     Warfarin) medication. The purpose of the study and all side
aging process; however, despite the endeavors to discover         effects of the intervention were clearly explained to all par-
the underlying mechanism, its pathogenesis is yet to be fully     ticipants. They were assured their information would remain
comprehended [5].                                                 confidential, and they were permitted to withdraw from
    Skin aging is categorized into two subgroups, which are       the study if they requested. Subsequently, written informed
intrinsic and extrinsic aging. Intrinsic aging progresses with    consent was obtained from all patients. The sample size was
age and can be described by epidermal thinning and fine           estimated based on a study by Sclafani et al [10], based on
wrinkles. However, deep wrinkles, hyperpigmentation, and          the mean wrinkles assessment score before and after the in-
skin laxity can be observed in extrinsic skin aging, which        tervention, taking into account the first type error of 5%,
is greatly impacted by chronic sun exposure. All in all, skin     80% power, and an effect size of 0.8, calculating to a total
wrinkles are the hallmark of skin aging [4, 6].                   of 15 participants.
    In recent years, many exogenous filler materials have
been put to the test in the hope of improving skin wrinkles       Intervention
by volume augmentation. The mainstay of filler disadvan-          For intervention, after evaluating the patient’s medication
tages is its absorbable nature, which reduces its effect over     and drug history, the total depth of wrinkles before injection
time. Among these methods, platelet-rich plasma (PRP) in-         was measured with the Visophysis device. Decosept and a
jection has recently attracted significant attention. PRP con-    tourniquet were applied, and a 15cc blood sample was taken
sists of concentrated platelet and growth factors obtained        with a syringe at a 15-degree angle from the brachial vein,
via venous blood centrifuge [7]. Platelet-rich fibrin matrix      transferred to three 5cc tubes, and immediately centrifuged
(PRFM) is the new PRP generation that is richer in growth         at 700 rpm for 5 minutes. Then, using a canola, except for
factor concentration, enabling it to have a significantly bet-    1 cm above the tubes, the rest of the plasma, which had a
ter outcome in stimulating angiogenesis, tissue regeneration,     gel-like consistency, was transferred to a 5-cc sterile syringe.
and wound healing. Moreover, PRFM induces mesenchymal             After this, PRF was transferred to 1 cc syringes by sterile
stem cell (MSC) migration to the site of injection, which         connection. Simultaneously with the beginning of the blood
bears imperative regenerative function [2].                       collection process, local anesthesia (Xyla P Cream, Tehran
    Currently, various exogenous fillers are utilized glob-       Chemie) was used at the injection site. The duration of lo-
ally, including in Iran. High cost, owing to the exogenous        cal anesthesia was at least 30 to 50 minutes, based on the
nature of the filler and transient side effects such as edema,    patients’ anesthesia capacity. After sterilizing the injection
erythema, encapsulation, granuloma formation, and even            site with betadine, a 3cc PRF solution was injected into the
chronic or delayed infection, minimizes its popularity [8].       wrinkles around the eyes with a canola number 27 on both
Conclusively, PRF as a natural autologous filler has the po-      sides. The injection was performed at the sub-dermis site and
tential to be a safe candidate with long-lasting effects.         in one session. The patients were advised to visit our clinic
                                                                  in case of delayed alleviation of swelling or adverse effects,

Objectives                                                        such as infection. Also, since the effectiveness of PRF was to
                                                                  be evaluated in our study, the use of creams or other prod-
Several studies have concluded that PRF is an effective           ucts was not recommended. Participants were also informed
route in reducing skin wrinkles with minimal side effects.        that they could also be present at work on the same day of
Its side effects are mainly limited to transient erythema at      the procedure without any problems.



2                                                                     Original Article | Dermatol Pract Concept. 2023;13(1):e2023050
Outcome Assessment                                                                                                       injection site for up to one day after the injection, which
The initial severity of periorbital wrinkles was determined by                                                           resolved without complications. We measured tissue depth
Visioface 1000D (CK electronic, manufactured in Germany),                                                                with a Visophysis device before and twelve weeks after injec-
and obtained data were delivered to the statistical unit for                                                             tion. During this period, none of the people had any compli-
statistical analysis. Scoring and evaluation were based on tis-                                                          cations and all were completely satisfied. The tissue volume
sue volume and depth and were measured before and twelve                                                                 score of the participants included in our study is demon-
weeks after injection. Patients were also advised to visit in                                                            strated in Figure 1. Also, Figure 2 demonstrates the cosmetic
case of developing any complications.                                                                                    appearance of the results of our study.
                                                                                                                                  There was no significant difference among the male and
Data Analysis                                                                                                            female groups regarding tissue volume before injection at
                                                                                                                         both sides. (P=0.964 and 0.240 for right and left, respec-
Data were entered into SPSS version 21 and subsequently
                                                                                                                         tively). Furthermore, As demonstrated in table 1, the tissue
analyzed. An independent sample t-test was used to evaluate
                                                                                                                         volume size on both sides significantly decreased, both in
the difference in tissue volume among the groups. A P-value
                                                                                                                         males and females, after PRF injection (Table 1). However,
of less than 0.05 was considered statistically significant.
                                                                                                                         there was no significant difference among males and females
                                                                                                                         regarding tissue volume after injection (P=0.784 and 0.427,
Ethical Considerations
                                                                                                                         for right and left, respectively) or amount of tissue volume
The study was approved by the Research Ethics Committee of
                                                                                                                         change (P=0.828 and 0.0339, for right and left, respectively)
the Shiraz University of Medical Sciences and was conducted
                                                                                                                                  It should be noted that following PRF injection, in addi-
in compliance with the relevant guidelines and regulations
                                                                                                                         tion to improving deep wrinkles, noticeable improvement was
and the Declaration of Helsinki. Written informed consent
                                                                                                                         observed in fine and small wrinkles, periocular hyperpigmen-
was obtained from the patients in our study. The purpose of
                                                                                                                         tation, and overall skin freshness of the injection site. All sub-
this research was completely explained to the patients, and
                                                                                                                         jective reports among our participants reported satisfaction
they were assured that their information would be kept con-
                                                                                                                         and were eager to repeat and recommend this procedure.
fidential by the researcher. The present study was approved
by the Medical Ethics Committee of the academy (Ethical
                                                                                                                         Discussion
Code: IR.SUMS.MED.REC.1400.480) and registered in the
clinical trials database (Code: IRCT20220218054054N1).                                                                   In recent years, platelet concentrates injection has gained
                                                                                                                         global popularity, which, combined with the increased de-
                                                                                                                         mand for skin rejuvenation techniques, calls for further clinical
Results
                                                                                                                         assessment of the safety and function of these products. PRF
Sixteen patients, consisting of eight males and eight females,                                                           is the new evolutionary face of platelet-rich ­aggregates [11].
were included in our study. Each participant was evaluated                                                               This study puts the effect of PRF under conduction and ob-
based on changes in the left and right side periorbital wrin-                                                            served significant improvement in periorbital skin rejuvena-
kles after PRF injection. The subjects had swelling in the                                                               tion accompanied by significant patient satisfaction.


  30
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  25                                                                                                                                                                                    23
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                                                                                                                                                               21    21
  20                                                  18                                                                                     18                 18
                                                                                             18
                               17
                                        15             16                                                                              15                                        15                 15
  15      14                             14 14                                                    14                                    14    14                      14           14    14    14
                   12                        13 13                                                                                                 13
                                                                                                                                                         12
                                                                                                                                                                           13
                                                                                                                                                                                                         12            12
                          11                     12         11       11                            11                             11                                        11
                    10                                                 10                                       10       10                         10    10                                                      10    10
  10                                                             9          9       9                   9            9        9    9                                                                 9
               8                    8                                           8                           8                                                                                                 8
                                                                                        7                                                                                                                          7

   5


   0
              1R    1L 2R   2L  3R   3L 4R   4L  5R   5L 6R   6L  7R   7L  8R   8L  9R   9L 10R 10L 11R 11L 12R 12L 13R 13L 14R 14L 15R 15L 16R 17L
          T       NT NT   NT NT    NT NT   NT NT    NT NT   NT NT    NT NT    NT NT    NT T     T   T   T   T   T  T    T   T   T   T   T   T   T
       EN       IE TIE TIE TIE TIE TIE TIE TIE TIE TIE TIE TIE TIE TIE TIE TIE TIE IEN IEN IEN IEN IEN IEN IEN IEN IEN IEN IEN IEN IEN IEN
     TI       T
   PA       PA PA      PA  PA  PA PA    PA PA   PA PA    PA  PA  PA PA    PA PA    PA PAT PAT PAT PAT PAT PAT PAT PAT PAT PAT PAT PAT PAT PAT

                                                                                                        BEFORE            AFTER



Figure 1. Changes in tissue volume before and after platelet-rich Fibrin injection among females (patients 1 to 8) and males (patients 9 to 16).



Original Article | Dermatol Pract Concept. 2023;13(1):e2023050                                                                                                                                                               3
Figure 2. Results of platelet-rich fibrin matrix in the correction of periorbital wrinkles.



                    Table 1. Tissue volume score and changes based on gender and laterality.
                                              Right                                                          Left
    Gender             Before            After          Change       P-value*         Before           After         Change       P-value*
Female; n= 15 14.88 ± 6.13 11.00 ± 3.59 3.88 ± 3.94                    0.027       13.13 ± 3.23 10.50 ± 2.88 2.63 ± 2.67            0.027
Male; n=15         15.00 ± 4.75 11.50 ± 3.59 3.50 ± 2.73               0.008       15.75 ± 5.12 11.63 ± 2.62 4.13 ± 3.36            0.010
P-value*               0.964             0.784           0.828            -            0.240          0.427           0.339            -

* Independent sample t-test



    PRF, the second generation of platelet concentrates, is                device. The results revealed significant improvement in deep
superior to PRP in numerous aspects. First of all, PRF prepa-              wrinkles in all candidates. Furthermore, noticeable improve-
ration consists of only one centrifugation step, making it                 ments were also noted in fine and small periorbital wrinkles.
simpler than PRP preparation [12]. As a result of declined                 This result is also in line with previous studies on the benefits
centrifuge speed, PRF has been observed to contain higher                  of PRF [11].
volumes of growth factors, leukocytes, fibrin, and platelets                   Along with the diminishing wrinkles, improvement in
than PRP, resulting in a more boosted growth factor-mediated               skin hyperpigmentation and overall freshness were also of
functional aftermath [11]. Secondly, PRF is completely autol-              significance. Maisel-Campbell et al. conducted a system-
ogous and does not contain any exogenous additives, which                  atic review of the benefits of PRP injection and observed
supports the natural physiologic polymerization of fibrin.                 significant improvement in skin texture through different
Growth factor binding and platelet capture are facilitated                 ­studies [14]. A Chinese study conducted on the effect of
via the three-dimensional fibrin structure of PRF that results             PRP injection also concluded that skin quality was signifi-
in the enhancement of the gradual and long-term release of                 cantly enhanced in participants with a substantial decline in
cytokines and growth factors. Moreover, this fibrin mesh is                wrinkles, pores, and texture. Furthermore, PRP treatment
also responsible for cell proliferation and differentiation and            was detected to inhibit UV‑B‑induced tyrosinase and metal-
the formation of new blood vessels [11, 12]. Finally, PRF                  loproteinase‑1 (MMP‑1) upregulation, which along with
prompts cell proliferation, migration, differentiation, and                tropoelastin and fibrillin induction, results in photoaging en-
adhesion accompanied by anti-inflammatory properties that                  hancement [15]. The benefits of platelet aggregate products
further support its therapeutic aptitude in bone regeneration,             take root from not only its high concentration of growth fac-
wound healing, improving scar appearance, and stimulating                  tors, but also its gelatin constituents. The gelatin part has the
hair growth [2, 13].                                                       potential to bring elasticity and a good support system for
    This study utilized a PRF solution for periorbital wrinkles,           wrinkles, cavities, and skin relaxation[16]. In addition, these
and the depth of the wrinkles was assessed via a Visophysis                platelet ­aggregate products contain cell adhesion proteins



4                                                                               Original Article | Dermatol Pract Concept. 2023;13(1):e2023050
which could help keep the skin tight and smooth [15]. The         higher sample sizes are warranted to understand the extent
decline in hyperpigmentation that was observed in our study       of improvement and also possible side effects.
is consistent with previous studies and is due to the fact that
platelet aggregate products increase skin thickness and ame-
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6                                                                             Original Article | Dermatol Pract Concept. 2023;13(1):e2023050
