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Plastic Surgery Focus: Special Topics

Platelet-Rich Plasma: Evolving Role in Plastic Surgery

Chamata, Edward S. M.D.; Bartlett, Erica L. M.D.; Weir, David N.P.-C.; Rohrich, Rod J. M.D.

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Plastic and Reconstructive Surgery: January 2021 - Volume 147 - Issue 1 - p 219-230
doi: 10.1097/PRS.0000000000007509
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Abstract

The use of platelet-rich plasma in the medical arena has grown exponentially in the past few years, with claims of regenerative and restorative properties. Originally used for the treatment of dermatologic and oromaxillofacial conditions, it has since grown within other clinical specialties such as orthopedic and plastic surgery.1 Dermatologic and plastic surgical uses include facial rejuvenation, androgenic alopecia, acne scarring, and fat grafting, among others.2 Studies have shown improvements in wrinkles, skin texture, facial volume, and hair regrowth.3 Other clinical trials have shown promising results with regard to tissue healing.4–7 Recent literature has emerged with objective measurements to delineate the true efficacy of platelet-rich plasma; however, a lack of large-scale studies exists.8 To date, no standardized protocol for platelet-rich plasma preparation and treatment has been established. Classification systems have been suggested to aid with standardization, but these have not yet been broadly implemented.3,9 In this article, we aim to discuss the proposed physiology, preparation, and clinical use of platelet-rich plasma, and to highlight the objective data supporting its widespread use.

Platelet Physiology and platelet-rich plasma Science

Platelets play a vital role in the initiation of hemostasis and wound healing, setting the pace for wound repair.10,11 In response to tissue and vascular damage, a platelet plug is formed, with subsequent release of biologically active proteins. These proteins, released from alpha-granules within the platelet, initiate a cascade of events leading to tissue healing and regeneration.12 Although constituting only 10 percent of platelet volume, over 30 biologically active proteins are released, including transforming growth factor-β, platelet-derived growth factor, vascular endothelial growth factor, fibroblast growth factor, and epithelial cell growth factor. These factors not only aid in coagulation but drive angiogenesis and promote wound repair.13–18 Proposed therapeutic effects from platelet-rich plasma result from locally released growth factors within the target tissue. Table 1 lists the common growth factors within platelet-rich plasma and their proposed mechanism of action.19–23

Table 1. - Platelet Factors and Their Function
Growth Factors Released by Platelets Function
VEGF19 • Promotes endothelial cell migration and proliferation
• Increases vascular permeability
• Promotes angiogenesis, epithelization, and collagen deposition
• Formation of granulation tissue
PDGF20 • Stimulates breakdown of old collagen
• Potent activator for cells of mesenchymal origin
• Stimulates chemotaxis, proliferation, and gene expression in monocytes-macrophages and fibroblasts
FGF21 • Initial stimulus for angiogenesis
• Plays role in tissue remodeling
• Promotes migration of fibroblasts
• Mitogen for vascular endothelial cells
EGF22 • Increases keratinocyte migration
• Enhances epithelialization
• Assists in granulation tissue formation
TGF-β23 • Mediates extracellular matrix production, collagen production
• Promotes angiogenesis
• Increases proliferation of fibroblasts and keratinocytes
• Inhibitor of metalloproteinase
VEGF, vascular endothelial growth factor; PDGF, platelet-derived growth factor; FGF, fibroblast growth factor; EGF, epidermal growth factor; TGF-β, transforming growth factor-β.

platelet-rich plasma Preparation

Platelet-rich plasma is defined as the plasma concentrate of autologous blood with a platelet quantity above normal physiologic level.24 Normal platelet concentrations in blood range from 150,000 to 450,000 platelets/mm3.25 Some studies report baseline platelet counts to standardize platelet-rich plasma concentrations. Clinically, this is not practical, as it adds unnecessary costs, and it is unclear whether this translates to higher efficacy.

Various forms of platelet-rich plasma exist as detailed in Table 2. These are classified based on the contents of the concentrate (i.e., leukocytes and/or platelets), and are also classified based on the density of the fibrin network that supports this leukocyte and platelet concentrate. Such variation in the final platelet-rich plasma product is attributable to a wide range of preparation protocols, differing in the number, force, and time of centrifugation.26,27 For the single-spin technique, a sample of whole blood is centrifuged, and three layers are formed because of different densities (Fig. 1). The bottom layer consists of red blood cells; the middle layer, known as the buffy coat, consists of platelets and leukocytes; and the top layer consists of plasma.18 Although the bottom layer is always discarded, the use of variable quantities of the buffy coat and plasma layer can yield different platelet concentrations. A second spin can further separate the solution, potentially creating a solution with a higher platelet concentration that either includes or excludes leukocytes, depending on the amount of buffy coat transferred to the second tube.9,26,28 For pure platelet-rich fibrin and leukocyte- and platelet-rich fibrin, a high-density fibrin-platelet clot is produced during the centrifugation process. It allows for slower release of growth factors over time and has been shown to dissolve more slowly than the low-density fibrin matrix of pure platelet-rich plasma or leukocyte- and platelet-rich plasma.27 In the literature, differing opinions exist on the role of leukocytes in platelet-rich plasma solution. Proponents of platelet-rich plasma high in leukocyte concentration discuss the importance of these leukocytes in immune regulation, infection prevention, and promotion of angiogenesis through release of vascular endothelial growth factor.26,29,30 Alternatively, studies that advocate for the exclusion of leukocytes argue that the inflammatory response produced by cytokine release from these leukocytes causes negative effects on the treated tissue.31,32

Table 2. - Platelet-Rich Preparations
Preparation Name Description
P-PRP • Platelet-rich
• Leukocyte-poor
• Low-density fibrin network
L-PRP • Platelet-rich
• Leukocyte-rich
• Low-density fibrin network
P-PRF • Platelet-rich
• Leukocyte-poor
• High-density fibrin network
L-PRF • Platelet-rich
• Leukocyte-rich
• High-density fibrin network
P-PRP, pure platelet-rich plasma; L-PRP, leukocyte- and platelet-rich plasma; P-PRF, pure platelet-rich fibrin; L-PRF, leukocyte- and platelet-rich fibrin.

Fig. 1.
Fig. 1.:
Three layers of centrifuged whole blood.

Three factors can be addressed when making platelet-rich plasma: anticoagulation, centrifugation, and activation. A generalized platelet-rich plasma preparation guide is listed in Figure 2.

Fig. 2.
Fig. 2.:
Platelet-rich plasma preparation overview.

Anticoagulation

Anticoagulation is used during the processing of whole blood to prevent clotting. Platelet-rich plasma is stable in the anticoagulated state for approximately 8 hours after its preparation.10,24,33 Coagulation can be halted by disabling calcium ions, which are necessary for clot formation in the coagulation cascade. This is done with the addition of citrate ion, which binds and deactivates calcium, forming calcium citrate. Many anticoagulants are used and include sodium citrate, acid citrate dextrose, citrate phosphate dextrose adenine, trisodium citrate, trisodium phosphate, and citrate. Most commercial platelet-rich plasma device venipuncture collection tubes are coated with an anticoagulant.

Centrifugation

Variation exists in the literature with regard to the number, force, and time of centrifugations performed.34,35 A standard laboratory centrifuge or commercial collecting system may be used for platelet-rich plasma preparation. These systems differ in the platelet concentration produced, with variable ranges based on the device used.18,24,36–38 Some collection systems also use a separator gel during the centrifugation process that provides a physical gradient for blood to pass through.39–41

During processing, platelet activation should be avoided as much as possible. Platelet fragmentation should also be avoided, as this can result in premature release of activated proteins, with poor bioactivity.36 To help prevent such fragmentation, low gravity forces during centrifugation can be implemented along with acid citrate dextrose anticoagulant, which preserves platelet membrane integrity.24,36

Activation

An exogenous activator can be added to the platelet-rich plasma to facilitate release of biologically active proteins. This is done with a calcium-based activator alone (e.g., calcium chloride), calcium gluconate, or thrombin. Calcium that was previously bound by the anticoagulant is replenished with the addition of calcium activator.15,39,42–45 Alternatively, thrombin functions by directly activating platelets.

Biologically active proteins are secreted from platelets within 10 minutes of clot initiation, and more than 95 percent of these presynthesized growth factors would have been secreted within the first hour.10,46 For this reason, delivery of platelet-rich plasma within 10 minutes is advised. Some studies do not activate platelets, arguing that this step is unnecessary and that platelets are ready to exert their function once injected.35,47–50 [See Video 1 (online), which demonstrates the preparation process of platelet-rich plasma.]

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Platelet and Growth Factor Concentration

No consensus exists for platelet concentration in platelet-rich plasma. Platelet concentrations of more than 1 million/µl are generally viewed as therapeutically effective; however, the literature is lacking.51,52 Reported platelet concentrations vary from 2- to 9-fold increase above baseline, but the ideal concentration of platelets has not been elucidated.10,36,38,53,54

Some studies report the platelet concentration in the platelet-rich plasma obtained; however, few report whole blood and platelet-rich plasma platelet levels.34,39,42,49,50,55–57 A dose-response relationship exists in vitro between concentration of platelets and human adult mesenchymal stem cell production, type I collagen production, and fibroblast proliferation; however, this has not been proven with clinical studies.58 Other studies question this dose-response relationship, theorizing that different individuals may require different platelet concentration ratios to achieve similar effects and that growth factor concentrations contained within platelets are variable between patients.44,59,60 In addition, there is some speculation that the treatment of different conditions requires different platelet concentrations.

Applications in Plastic Surgery

The regenerative ability of platelet-rich plasma has been used in multiple areas within plastic surgery and has been extensively documented in the literature. These include skin rejuvenation, treatment of acne scars, alopecia, laser, and fat grafting.

Skin Rejuvenation

Rejuvenation of the aging facial skin is a common indication for the use of platelet-rich plasma. This is related to growth factor stimulation and activation of dermal fibroblasts, which in turn induce collagen synthesis and subsequent remodeling of the extracellular matrix.54

Injection

Historically, platelet-rich plasma was injected intradermally and/or subdermally, with improvement in skin texture, color, and reduced wrinkle depth.35 Some of the original work showed a statistically significant increase in dermal collagen levels with intradermal platelet-rich plasma injection compared with saline.61 Additional neocollagenesis results from the needling effect, which is found to maximize the results.62 Excellent results have been achieved with this modality; however, procedural pain and downtime are higher compared to topical application.63

Topical

Currently, a popular technique for skin rejuvenation involves the application of topical platelet-rich plasma after microneedling.64 This stems from the concept of mesotherapy, which uses multiple small intradermal punctures to facilitate absorption of topical medications. Not only used to facilitate platelet-rich plasma delivery, microneedling creates superficial dermal injury at varying depths, which has been shown to increase collagen production, skin tightening, and rejuvenation. There are multiple microneedling devices currently used; however, the SkinPen (Bellus Medical, Addison, Texas) is the only microneedling device cleared by the U.S. Food and Drug Administration. These devices are applied numerous times over the face, in various directions, at various depths, until the endpoint of erythema with or without pinpoint bleeding is reached. [See Video 2 (online), which demonstrates microneedling performed for facial rejuvenation.] When platelet-rich plasma is combined with microneedling, the effects were found to be magnified.65 Studies have shown increased organized and compact collagen with diminished abnormal elastin fibers with combination microneedling and platelet-rich plasma compared to microneedling alone.66

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Treatment with microneedling in conjunction with platelet-rich plasma has also emerged for treatment of atrophic acne scars.42,67,68 Microneedling has been used for treatment of facial scars, including ice pick, boxcar, and rolling scars; however, the addition of platelet-rich plasma has shown profound improvement in appearance. In a split-face trial of microneedling with platelet-rich plasma compared to microneedling alone, significant improvement in appearance and quality of life was achieved in the combination group.69

Likewise, skin pigmentation disorders have been successfully treated with platelet-rich plasma. Statistically significant improvement of melasma, both epidermal and mixed types, has been shown after treatment with topical platelet-rich plasma.68,70 Infraorbital skin hyperpigmentation has shown statistical improvement, despite no significant change in melanin content.68

Variability exists with regard to the number of treatments and time intervals between treatments. Such procedures can be performed once, or every 4 to 6 weeks and repeated several times, depending on the results desired. The average treatment recommendation is three sessions to maximize therapeutic results and varies based on the treatment goal. Table 3 lists the studies evaluating platelet-rich plasma and facial rejuvenation.

Table 3. - Studies of Platelet-Rich Plasma and Facial Rejuvenation
Reference Study Type Volume of Whole Blood (ml) Final Volume of PRP Injected (ml) Platelet Concentration above Baseline Injection Technique No. of Treatments Findings
Redaelli et al., 201041 Case series 16 3.08 Not reported Direct injection 3 • Improved skin texture and elasticity
• Increased volume
• Decreased acne scarring
• Increased patient satisfaction
Sclafani, 201040 Case series 18 2–5 Not reported Direct injection 1 • Improvement in wrinkle severity scores
Yuksel et al., 201435 Case series 8 1.5 Not reported Direct injection and topical 3 • Improved skin general appearance
• Decreased wrinkles
• Increased skin firmness
Mehryan et al., 201468 Case series 10 1.5 Not reported Direct injection 3 • Improved infraorbital color
• Increased patient satisfaction
Kang et al., 201455 Prospective, randomized, split-face trial 12 1 Not reported Direct injection 3 • Decreased wrinkles
• Improved skin tone
• Decreased erythema and melanin
Diaz-Ley et al., 201583 Case series 36 Not reported Not reported Direct injection 3 • Increase in skin thickness
• Decrease solar elastosis
Sevilla et al., 201549 Case series 34 5 Not reported Direct injection 1 • Decrease nasolabial fold severity
Abuaf et al, 201661 Prospective, nonrandomized, controlled trial 8 2 Not reported Direct injection 1 • Increased dermal collagen
Cameli et al., 201764 Case series 9 4 Not reported Direct injection 3 • Improved skin texture
• Improved skin elasticity
• Improved skin barrier function
Elnehrawy et al., 2017108 Case series 18 5–6 Not reported Direct injection 1 • Decreased wrinkle severity
• Improved skin texture
Gawdat at al., 201763 Prospective, randomized, split-face trial 10 2 Not reported Direct injection 6 • Increased skin thickness texture
• High patient satisfaction
El-Domyati et al., 201866 Prospective, randomized, split-face trial 10 Not reported Not reported Topical after microneedling 6 • Increased skin thickness
• Increase in organized collagen
Everts et al., 201829 Case series 50 7 Not reported Direct injection 3 • Decrease in brown spots
• Decrease wrinkles
• Increase skin firmness
• High patient satisfaction
Lee et al., 2018109 Case series 8 4 Not reported Direct injection 1 • High patient satisfaction
PRP, platelet-rich plasma.

Alopecia

The use of platelet-rich plasma for the treatment of androgenic alopecia holds some of the strongest and most convincing evidence for successful hair restoration. This is because of the use of quantitative measurements such as hair counts, immunohistochemistry, and dermoscopic photomicrographs in reporting outcomes. Platelet-rich plasma increases proliferation rates of human dermal papilla cells that regulate hair follicle growth. Through binding of growth factors and interactions between dermal papilla cells and primitive stem cells, activation of the proliferative phase of the hair cycle begins, leading to hair follicle formation and maintenance. The anagen phase of the hair cycle is thus maintained with a delay in progression to the catagen phase, which over time leads to an overall increase in hair density.71 [See Video 3 (online), which demonstrates the injection of platelet-rich plasma for androgenic alopecia.]

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Platelet-rich plasma may be used as a standalone treatment or combined with hair transplantation for the treatment of androgenic alopecia. During hair transplantation, approximately 70 to 85 percent of implanted micrografts will remain because of apoptosis of hair follicles.72 In a split-scalp study, Uebel et al. investigated the efficacy of micrografts imbibed with platelet-rich plasma in improving graft take after hair transplantation, and showed a 15.1 percent average increase in follicular unit density with the use of platelet-rich plasma.72 Another split-scalp study in patients with alopecia areata used immunohistochemical staining to measure Ki-67 levels, a marker of cellular proliferation, and showed a significant increase in both Ki-67 levels and hair regrowth with the use of platelet-rich plasma compared to the placebo side.73

A number of prospective studies have shown significant improvements in alopecia.57,74–77 A meta-analysis including six small studies with a total of 194 patients treated with platelet-rich plasma for alopecia showed a significant increase in number of hairs per square centimeter.78

A recent systematic review of 19 studies looking at platelet-rich plasma preparation for androgenic alopecia showed a 3.8-fold average increase in platelet concentration over baseline; however, this value ranged from 2-fold to 5.9-fold among the studies reporting platelet count of whole blood and platelet-rich plasma.79 Several randomized, double-blind, placebo-controlled studies have yielded favorable results in terms of hair count and hair density, with platelet concentrations ranging anywhere from three to five times above that of baseline in those studies.73,80,81Table 4 summarizes available studies using platelet-rich plasma to treat alopecia.

Table 4. - Overview of Studies with Platelet-Rich Plasma for Alopecia
Reference Study Type Volume of Whole Blood (ml) Final Volume of PRP Injected (ml) Platelet Concentration above Baseline Injection Technique Findings
Uebel et al., 200672 Split-scalp study 80 16 4–6× Follicular units soaked in PRP • Increase in follicular density
Khatu et al., 201474 Prospective 20 2–3 Not reported Nappage • Reduction in hair loss
• Increased hair count
• Negative hair pull test
Trink et al., 201373 RCT, split-scalp study 36 Not reported 3–5× N/A • Increase hair regrowth
• Decrease hair dystrophy
• Higher Ki-67 levels with PRP
Ferrando et al., 201775 Prospective 18 3 Not reported Nappage • Most showed improved grade for Ebling’s scale
Jha et al., 201884 Prospective 15 Not reported Not reported Nappage • Hair growth started after first session
• Increase in number of vellus and total hairs
• Increased hair shaft diameter
• Negative hair pull test
Singhal et al., 201557 Prospective 20 8–12 Not reported Nappage • Clinical improvement in hair count, hair thickness, hair root strength, and overall alopecia
Gkini et al., 201439 Prospective cohort 16 6 5.8× Nappage • Reduced hair loss
• Hair density peaked at 3 mo
• Significantly increased hair density at 6 mo and 1 yr
Kachhawa et al., 201776 Prospective, split-scalp study 16 1–2 Not reported Nappage • Hair loss reduced
• New hair growth
• Improved hair density, quality, and thickness
Alves and Grimalt, 201681 RCT, split-scalp study 18 3 Nappage • Improvement in mean anagen hairs, telogen hairs, hair density, and terminal hair density compared with baseline
Butt et al., 201885 Prospective 9 Not reported Not reported Nappage • Clinical improvement in hair counts, hair thickness, hair root strength, and overall alopecia
Rodrigues et al., 201880 RCT 51 2 Nappage • Significant increase in hair count, hair density, and percentage of anagen hairs
• No correlation with platelet counts or quantification of the growth factors in PRP
Gentile et al., 201534 RCT 78 9 Not reported Nappage • Improvement in mean number of hairs and hair density
• Increase in Ki-67+ bulge cells and increase in vessels around hair follicles
• 4 of 20 patients with relapse 12 mo after last treatment
PRP, platelet-rich plasma; RCT, randomized controlled trial; N/A, not applicable.

Although some study designs evaluating the effect of platelet-rich plasma on hair growth exclude patients that are currently undergoing treatment of androgenic alopecia with other modalities such as topical medications, oral medications, or low-level light therapy,39,56,57,76,81 other studies advocate for their continued use as adjuncts to platelet-rich plasma treatments.28,71,74,75,77,82 A positive additive effect may result by combining such treatments, as platelet-rich plasma differs in its mechanism of action from these other modalities and does not suppress the hormonal component of androgenic alopecia in the same fashion as minoxidil and finasteride.28,71,75,82 Long-term studies comparing the efficacy of combination therapy versus monotherapy may be beneficial in determining the need for continuation of medical therapy alongside platelet-rich plasma injections for the treatment of androgenic alopecia.

A common method of performing platelet-rich plasma injections to the scalp is with multiple 0.05- to 0.1-cc/cm2 subcutaneous injections, in a linear pattern, 1 cm apart, known as the “nappage technique.”39,57,74–81,84,85 [See Video 4 (online), which demonstrates the nappage technique for platelet-rich plasma hair injection.] Treatment is usually performed several times, with intervals ranging from 1 week to 1 month. Some protocols also recommend continued maintenance therapy after the initial treatment sessions to maintain the anagen phase of the hair growth cycle.39,75 Gkini et al. demonstrated a peak of hair density at 3 months after initial treatment, which began declining at 6 months; therefore, a booster treatment was administered at 6 months to maintain the results achieved. In that study, hair density at 1-year follow-up remained significantly higher than that of baseline but continued a downward trend.39 Gentile et al. also noted progressive hair loss in four of 20 patients at the 12-month evaluation mark, which was more evident 16 months after the last treatment; therefore, these patients were re-treated with three more sessions.34 Ferrando et al. recommend periodic treatments of two to three times per year after the initial treatment sessions for the most effective treatment, similar to our treatment recommendations.75 In both of these studies, patients were not followed long-term after receiving these booster sessions, thus emphasizing the need for studies with longer follow-up to evaluate the efficacy and longevity of such treatments.39,86,87

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Laser

Laser therapy has been combined with platelet-rich plasma to enhance results, with studies showing a therapeutic role in the treatment of acne scarring and facial aging. Platelet-rich plasma can be injected intradermally after laser therapy to provide a synergistic result, although it is used topically by a smaller portion of the studies.88–90 Not only does it provide local growth factors for healing, it has been demonstrated to decrease the intensity of erythema after laser treatment and accelerate epithelialization.63,86,87,91 For both acne scarring and facial rejuvenation, fractional lasers such as carbon dioxide or erbium have been used, as they can penetrate at depths that stimulate neocollagenesis but have less thermal injury than the traditional ablative subtype.92 Positive results for facial aging treated with platelet-rich plasma and laser therapy are demonstrated as early as one treatment, but in other studies, three sessions were used for maximum results.89 Histologically, a higher proportion of fibroblasts and volume of collagen was demonstrated when combined with platelet-rich plasma. Clinically, Shin et al. reported statistically significant improvement in skin elasticity for patients receiving combination therapy.87 Also demonstrated was a more obvious improvement in skin color, texture, and pore size.89 Treatment for acne scarring consists of a series of treatments, ranging from two to three monthly sessions. Gawdat et al. showed a significant improvement in the treatment response for atrophic acne scars at 6-month follow-up when platelet-rich plasma was used in combination with fractional carbon dioxide.63 Confirmed by other split-face randomized controlled trials, acne scarring showed a higher level of improvement of scar depth and pigmentation, confirming its synergetic effects.92

Fat Grafting

Platelet-rich plasma can also be used in combination with fat grafting, with the theoretical benefit of increasing fat graft take. Although most of the presynthesized growth factors are secreted within 10 minutes of activation, platelets continue to synthesize and secrete additional growth factors for at least 5 to 7 days after.18,26,27 Theoretically, this would supply a local concentration of growth factors to promote neovascularization and tissue regeneration, particularly during the period of ischemia after fat injection.93–95 Multiple animal studies have confirmed the role of growth factors in angiogenesis and de novo adipogenesis, along with higher fat graft retention rates.96–99 Human studies have mainly been observational but have shown a favorable trend with fat graft retention.93,94,100 Variability exists in the literature with regard to platelet-rich plasma preparation and platelet-rich plasma–to-fat ratios. The largest systematic review to date of platelet-rich plasma and fat grafting reviewed 23 clinical studies: 21 human and two animal studies. They discuss that technical factors vary significantly between studies, making meaningful evaluation a challenge.101 Many of the human studies demonstrate higher fat graft retention rates on the face, based on observation alone.93,102 Cervelli et al. found a 70 percent maintenance of contour and volume after 1 year compared with 31 percent with just fat grafting alone.103 However, other studies using advanced imaging to evaluate fat maintenance percentages showed mixed results.34,104 Platelet-rich plasma–to-fat ratios vary widely in the literature and may account for some of the variation in results. Most studies use a range of 0.2 to 0.5:1 of platelet-rich plasma to fat, with one large review theorizing that a 0.5:1 ratio is the ideal platelet-rich plasma–to-fat ratio.99 Despite inconsistency in methodology, a majority of the data are in favor of the beneficial effects of platelet-rich plasma on fat graft retention.

Safety and Adverse Effects

As platelet-rich plasma is an autologous product, it is considered safe and free from communicable diseases.105 Sterility should be confirmed; however, this is less of a concern with commercial devices, as inadvertent handling is minimized. No serious complications have been reported with the use of platelet-rich plasma. Minor complications include transient edema, bruising, erythema and crusting, all of which are injection-related.106 Subjective feeling of skin tightness is transient. Although there is a theoretical risk of injecting platelet-rich plasma into a vessel, no such complications have been reported. There has been some literature suggesting that platelet-rich plasma can increase pigmentation in certain individuals with postinflammatory hyperpigmentation; thus, one should manage these patients with caution.107

Shortcomings and Lack of data

Ideally, universal agreement regarding preparation and administration should exist. A number of variables play a role on the ultimate effect of platelet-rich plasma on wound healing, and for this reason, little consensus exists with regard to the best method of platelet-rich plasma implementation. Some important aspects of platelet-rich plasma preparation include volume of blood collected, anticoagulant used, centrifugation speed, centrifugation time, number of spins, activating agent, and final volume of plasma. The type of problem being treated and the patient’s health condition may also play a part in the treatment efficacy.

A lack of objective outcomes reporting exists in the majority of studies to date. Many studies rely on comparison of pretreatment and posttreatment photographs to measure outcomes, assessed by either a physician or an investigator, with some studies implementing the use of a blinded evaluator. Patient self-assessment and/or patient satisfaction surveys were also used in a majority of studies as a method of reporting results. More objective assessment methods include histopathologic evaluation using immunohistochemistry, skin surface analyzers to quantify wrinkles, and digital imaging analysis to measure hair growth, among other tools.34,56,68,83 The use of objective outcome measures provides an opportunity for study reproducibility and comparison in technique.

CONCLUSIONS

The use of platelet-rich plasma has grown in plastic surgery because of better understanding of its regenerative and restorative effects. A diverse collection of literature exists in support of its use, displaying favorable results for skin rejuvenation, hair regrowth, wound healing, and fat graft take. Multiple variations in platelet-rich plasma protocols limit a standardized analysis of the results, however. Standardization of preparation, administration, and frequency will be necessary to evaluate and compare true objective outcomes, along with further large-scale studies with long-term follow-up to elucidate the true benefit of this treatment modality.

REFERENCES

1. Hsu WK, Mishra A, Rodeo SR, et al. Platelet-rich plasma in orthopaedic applications: Evidence-based recommendations for treatment. J Am Acad Orthop Surg. 2013;21:739–748.
2. Motosko CC, Khouri KS, Poudrier G, Sinno S, Hazen A. Evaluating platelet-rich therapy for facial aesthetics and alopecia: A critical review of the literature. Plast Reconstr Surg. 2018;141:1115–1123.
3. Frautschi RS, Hashem AM, Halasa B, Cakmakoglu C, Zins JE. Current evidence for clinical efficacy of platelet rich plasma in aesthetic surgery: A systematic review. Aesthet Surg J. 2017;37:353–362.
4. Anitua E. Plasma rich in growth factors: Preliminary results of use in the preparation of future sites for implants. Int J Oral Maxillofac Implants. 1999;14:529–535.
5. DelRossi AJ, Cernaianu AC, Vertrees RA, et al. Platelet-rich plasma reduces postoperative blood loss after cardiopulmonary bypass. J Thorac Cardiovasc Surg. 1990;100:281–286.
6. Hee HT, Majd ME, Holt RT, Myers L. Do autologous growth factors enhance transforaminal lumbar interbody fusion? Eur Spine J. 2003;12:400–407.
7. Margolis DJ, Kantor J, Santanna J, Strom BL, Berlin JA. Effectiveness of platelet releasate for the treatment of diabetic neuropathic foot ulcers. Diabetes Care. 2001;24:483–488.
8. Leo MS, Kumar AS, Kirit R, Konathan R, Sivamani RK. Systematic review of the use of platelet-rich plasma in aesthetic dermatology. J Cosmet Dermatol. 2015;14:315–323.
9. Mautner K, Malanga GA, Smith J, et al. A call for a standard classification system for future biologic research: The rationale for new PRP nomenclature. PM R. 2015;7(Suppl):S53–S59.
10. Marx RE. Platelet-rich plasma: Evidence to support its use. J Oral Maxillofac Surg. 2004;62:489–496.
11. Tischler M. Platelet rich plasma: The use of autologous growth factors to enhance bone and soft tissue grafts. N Y State Dent J. 2002;68:22–24.
12. Harrison P, Cramer EM. Platelet alpha-granules. Blood Rev. 1993;7:52–62.
13. Cho EB, Park GS, Park SS, et al. Effect of platelet-rich plasma on proliferation and migration in human dermal fibroblasts. J Cosmet Dermatol. 2019;18:1105–1112.
14. Zhang M, Park G, Zhou B, Luo D. Applications and efficacy of platelet-rich plasma in dermatology: A clinical review. J Cosmet Dermatol. 2018;17:660–665.
15. Bhanot S, Alex JC. Current applications of platelet gels in facial plastic surgery. Facial Plast Surg. 2002;18:27–33.
16. Anitua E, Andia I, Ardanza B, Nurden P, Nurden AT. Autologous platelets as a source of proteins for healing and tissue regeneration. Thromb Haemost. 2004;91:4–15.
17. Buckwalter JA. Effects of early motion on healing of musculoskeletal tissues. Hand Clin. 1996;12:13–24.
18. Eppley BL, Pietrzak WS, Blanton M. Platelet-rich plasma: A review of biology and applications in plastic surgery. Plast Reconstr Surg. 2006;118:147e–159e.
19. Bao P, Kodra A, Tomic-Canic M, Golinko MS, Ehrlich HP, Brem H. The role of vascular endothelial growth factor in wound healing. J Surg Res. 2009;153:347–358.
20. Pierce GF, Mustoe TA, Altrock BW, Deuel TF, Thomason A. Role of platelet-derived growth factor in wound healing. J Cell Biochem. 1991;45:319–326.
21. Akita S, Akino K, Hirano A. Basic fibroblast growth factor in scarless wound healing. Adv Wound Care (New Rochelle). 2013;2:44–49.
22. Bodnar RJ. Epidermal growth factor and epidermal growth factor receptor: The yin and yang in the treatment of cutaneous wounds and cancer. Adv Wound Care (New Rochelle). 2013;2:24–29.
23. Pakyari M, Farrokhi A, Maharlooei MK, Ghahary A. Critical role of transforming growth factor beta in different phases of wound healing. Adv Wound Care (New Rochelle). 2013;2:215–224.
24. Marx RE. Platelet-rich plasma (PRP): What is PRP and what is not PRP? Implant Dent. 2001;10:225–228.
25. Dhurat R, Sukesh M. Principles and methods of preparation of platelet-rich plasma: A review and author’s perspective. J Cutan Aesthet Surg. 2014;7:189–197.
26. Dohan Ehrenfest DM, Rasmusson L, Albrektsson T. Classification of platelet concentrates: From pure platelet-rich plasma (P-PRP) to leucocyte- and platelet-rich fibrin (L-PRF). Trends Biotechnol. 2009;27:158–167.
27. Dohan Ehrenfest DM, Bielecki T, Jimbo R, et al. Do the fibrin architecture and leukocyte content influence the growth factor release of platelet concentrates? An evidence-based answer comparing a pure platelet-rich plasma (P-PRP) gel and a leukocyte- and platelet-rich fibrin (L-PRF). Curr Pharm Biotechnol. 2012;13:1145–1152.
28. Stevens J, Khetarpal S. Platelet-rich plasma for androgenetic alopecia: A review of the literature and proposed treatment protocol. Int J Womens Dermatol. 2019;5:46–51.
29. Everts PA, van Zundert A, Schonberger JP, Devilee RJ, Knape JT. What do we use: Platelet-rich plasma or platelet-leukocyte gel? J Biomed Mater Res A. 2008;85:1135–1136.
30. Cieslik-Bielecka A, Gazdzik TS, Bielecki TM, Cieslik T. Why the platelet-rich gel has antimicrobial activity? Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2007;103:303–305; author reply 305–306
31. Zhou Y, Zhang J, Wu H, Hogan MV, Wang JH. The differential effects of leukocyte-containing and pure platelet-rich plasma (PRP) on tendon stem/progenitor cells: Implications of PRP application for the clinical treatment of tendon injuries. Stem Cell Res Ther. 2015;6:173.
32. Dragoo JL, Braun HJ, Durham JL, et al. Comparison of the acute inflammatory response of two commercial platelet-rich plasma systems in healthy rabbit tendons. Am J Sports Med. 2012;40:1274–1281.
33. Anderson NA, Pamphilon DH, Tandy NJ, Saunders J, Fraser ID. Comparison of platelet-rich plasma collection using the Haemonetics PCS and Baxter Autopheresis C. Vox Sang. 1991;60:155–158.
34. Gentile P, Garcovich S, Bielli A, Scioli MG, 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.
35. Yuksel EP, Sahin G, Aydin F, Senturk N, Turanli AY. Evaluation of effects of platelet-rich plasma on human facial skin. J Cosmet Laser Ther. 2014;16:206–208.
36. Gonshor A. Technique for producing platelet-rich plasma and platelet concentrate: Background and process. Int J Periodontics Restorative Dent. 2002;22:547–557.
37. Alves R, Grimalt R. A review of platelet-rich plasma: History, biology, mechanism of action, and classification. Skin Appendage Disord. 2018;4:18–24.
38. Kevy SV, Jacobson MS. Comparison of methods for point of care preparation of autologous platelet gel. J Extra Corpor Technol. 2004;36:28–35.
39. Gkini MA, Kouskoukis AE, Tripsianis G, Rigopoulos D, Kouskoukis K. Study of platelet-rich plasma injections in the treatment of androgenetic alopecia through a one-year period. J Cutan Aesthet Surg. 2014;7:213–219.
40. Sclafani AP. Platelet-rich fibrin matrix for improvement of deep nasolabial folds. J Cosmet Dermatol. 2010;9:66–71.
41. Redaelli A, Romano D, Marcianó A. Face and neck revitalization with platelet-rich plasma (PRP): Clinical outcome in a series of 23 consecutively treated patients. J Drugs Dermatol. 2010;9:466–472.
42. Chawla S. Split face comparative study of microneedling with PRP versus microneedling with vitamin C in treating atrophic post acne scars. J Cutan Aesthet Surg. 2014;7:209–212.
43. Man D, Plosker H, Winland-Brown JE. The use of autologous platelet-rich plasma (platelet gel) and autologous platelet-poor plasma (fibrin glue) in cosmetic surgery. Plast Reconstr Surg. 2001;107:229–237; discussion 238–239.
44. Eppley BL, Woodell JE, Higgins J. Platelet quantification and growth factor analysis from platelet-rich plasma: Implications for wound healing. Plast Reconstr Surg. 2004;114:1502–1508.
45. Marx RE, Carlson ER, Eichstaedt RM, Schimmele SR, Strauss JE, Georgeff KR. Platelet-rich plasma: Growth factor enhancement for bone grafts. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1998;85:638–646.
46. Braccini F, Chignon-Sicard B, Volpei Ch, Choukroun J. Modern lipostructure: The use of platelet rich fibrin (PRF). Rev Laryngol Otol Rhinol (Bord.). 2013;134:231–235.
47. Abdali H, Hadilou M. Treatment of nasolabial fold with subdermal dissection and autologous fat injection added with platelet-rich plasma. J Res Med Sci. 2014;19:1110.
48. Marwah M, Godse K, Patil S, Nadkarni N. Is there sufficient research data to use platelet-rich plasma in dermatology? Int J Trichology. 2014;6:35–36.
49. Sevilla GP, Dhurat RS, Shetty G, Kadam PP, Totey SM. Safety and efficacy of growth factor concentrate in the treatment of nasolabial fold correction: Split face pilot study. Indian J Dermatol. 2015;60:520.
50. Sasaki GH. The safety and efficacy of cell-assisted fat grafting to traditional fat grafting in the anterior mid-face: An indirect assessment by 3D imaging. Aesthetic Plast Surg. 2015;39:833–846.
51. Li ZJ, Choi HI, Choi DK, et al. Autologous platelet-rich plasma: A potential therapeutic tool for promoting hair growth. Dermatol Surg. 2012;38:1040–1046.
52. Giusti I, Rughetti A, D’Ascenzo S, et al. Identification of an optimal concentration of platelet gel for promoting angiogenesis in human endothelial cells. Transfusion. 2009;49:771–778.
53. Weibrich G, Kleis WK, Kunz-Kostomanolakis M, Loos AH, Wagner W. Correlation of platelet concentration in platelet-rich plasma to the extraction method, age, sex, and platelet count of the donor. Int J Oral Maxillofac Implants. 2001;16:693–699.
54. Kim DH, Je YJ, Kim CD, et al. Can platelet-rich plasma be used for skin rejuvenation? Evaluation of effects of platelet-rich plasma on human dermal fibroblast. Ann Dermatol. 2011;23:424–431.
55. Kang BK, Shin MK, Lee JH, Kim NI. Effects of platelet-rich plasma on wrinkles and skin tone in Asian lower eyelid skin: Preliminary results from a prospective, randomised, split-face trial. Eur J Dermatol. 2014;24:100–101.
56. Cervelli V, Garcovich S, Bielli A, et al. The effect of autologous activated platelet rich plasma (AA-PRP) injection on pattern hair loss: Clinical and histomorphometric evaluation. Biomed Res Int. 2014;2014:760709.
57. Singhal P, Agarwal S, Dhot PS, Sayal SK. Efficacy of platelet-rich plasma in treatment of androgenic alopecia. Asian J Transfus Sci. 2015;9:159–162.
58. Liu Y, Kalén A, Risto O, Wahlström O. Fibroblast proliferation due to exposure to a platelet concentrate in vitro is pH dependent. Wound Repair Regen. 2002;10:336–340.
59. Weibrich G, Kleis WK, Hafner G. Growth factor levels in the platelet-rich plasma produced by 2 different methods: Curasan-type PRP kit versus PCCS PRP system. Int J Oral Maxillofac Implants. 2002;17:184–190.
60. Weibrich G, Kleis WK, Hafner G, Hitzler WE. Growth factor levels in platelet-rich plasma and correlations with donor age, sex, and platelet count. J Craniomaxillofac Surg. 2002;30:97–102.
61. Abuaf OK, Yildiz H, Baloglu H, Bilgili ME, Simsek HA, Dogan B. Histologic evidence of new collagen formulation using platelet rich plasma in skin rejuvenation: A prospective controlled clinical study. Ann Dermatol. 2016;28:718–724.
62. Nofal E, Helmy A, Nofal A, Alakad R, Nasr M. Platelet-rich plasma versus CROSS technique with 100% trichloroacetic acid versus combined skin needling and platelet rich plasma in the treatment of atrophic acne scars: A comparative study. Dermatol Surg. 2014;40:864–873.
63. Gawdat HI, Hegazy RA, Fawzy MM, Fathy M. Autologous platelet rich plasma: Topical versus intradermal after fractional ablative carbon dioxide laser treatment of atrophic acne scars. Dermatol Surg. 2014;40:152–161.
64. Cameli N, Mariano M, Cordone I, Abril E, Masi S, Foddai ML. Autologous pure platelet-rich plasma dermal injections for facial skin rejuvenation: Clinical, instrumental, and flow cytometry assessment. Dermatol Surg. 2017;43:826–835.
65. Asif M, Kanodia S, Singh K. Combined autologous platelet-rich plasma with microneedling verses microneedling with distilled water in the treatment of atrophic acne scars: A concurrent split-face study. J Cosmet Dermatol. 2016;15:434–443.
66. El-Domyati M, Abdel-Wahab H, Hossam A. Microneedling combined with platelet-rich plasma or trichloroacetic acid peeling for management of acne scarring: A split-face clinical and histologic comparison. J Cosmet Dermatol. 2018;17:73–83.
67. Keyhan SO, Hemmat S, Badri AA, Abdeshahzadeh A, Khiabani K. Use of platelet-rich fibrin and platelet-rich plasma in combination with fat graft: Which is more effective during facial lipostructure? J Oral Maxillofac Surg. 2013;71:610–621.
68. Mehryan P, Zartab H, Rajabi A, Pazhoohi N, Firooz A. Assessment of efficacy of platelet-rich plasma (PRP) on infraorbital dark circles and crow’s feet wrinkles. J Cosmet Dermatol. 2014;13:72–78.
69. Porwal S, Chahar YS, Singh PK. A comparative study of combined Dermaroller and platelet-rich plasma versus Dermaroller alone in acne scars and assessment of quality of life before and after treatment. Indian J Dermatol. 2018;63:403–408.
70. Hofny ERM, Abdel-Motaleb AA, Ghazally A, Ahmed AM, Hussein MRA. Platelet rich plasma is a useful therapeutic option in melasma. J Dermatolog Treat. 2019;30:396–401.
71. Garg S, Manchanda S. Platelet-rich plasma: An ‘elixir’ for treatment of alopecia: Personal experience on 117 patients with review of literature. Stem Cell Investig. 2017;4:64.
72. Uebel CO, da Silva JB, Cantarelli D, Martins P. The role of platelet plasma growth factors in male pattern baldness surgery. Plast Reconstr Surg. 2006;118:1458–1466; discussion 1467.
73. Trink A, Sorbellini E, Bezzola P, et al. 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.
74. Khatu SS, More YE, Gokhale NR, Chavhan DC, Bendsure N. Platelet-rich plasma in androgenic alopecia: Myth or an effective tool. J Cutan Aesthet Surg. 2014;7:107–110.
75. Ferrando J, García-García SC, González-de-Cossío AC, Bou L, Navarra E. A proposal of an effective platelet-rich plasma protocol for the treatment of androgenetic alopecia. Int J Trichology. 2017;9:165–170.
76. Kachhawa D, Vats G, Sonare D, Rao P, Khuraiya S, Kataiya R. A spilt head study of efficacy of placebo versus platelet-rich plasma injections in the treatment of androgenic alopecia. J Cutan Aesthet Surg. 2017;10:86–89.
77. Jha AK, Udayan UK, Roy PK, Amar AKJ, Chaudhary RKP. Original article: Platelet-rich plasma with microneedling in androgenetic alopecia along with dermoscopic pre- and post-treatment evaluation. J Cosmet Dermatol. 2018;17:313–318.
78. Giordano S, Romeo M, di Summa P, Salval A, Lankinen P. A meta-analysis on evidence of platelet-rich plasma for androgenetic alopecia. Int J Trichology. 2018;10:1–10.
79. Kramer ME, Keaney TC. Systematic review of platelet-rich plasma (PRP) preparation and composition for the treatment of androgenetic alopecia. J Cosmet Dermatol. 2018;17:666–671.
80. Rodrigues BL, Montalvão SAL, Cancela RBB, et al. 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.
81. 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.
82. Borhan R, Gasnier C, Reygagne P. Autologous platelet rich plasma as a treatment of male androgenetic alopecia: Study of 14 cases. J Clin Exp Dermatol Res. 2015;6:292.
83. Díaz-Ley B, Cuevast J, Alonso-Castro L, et al. Benefits of plasma rich in growth factors (PRGF) in skin photodamage: Clinical response and histological assessment. Dermatol Ther. 2015;28:258–263.
84. Jha AK, Sonthalia S, Jakhar D. Platelet rich plasma with microneedling and trichloroacetic acid peel for treatment of striae distensae. J Am Acad Dermatol. 2018;79:e107–e108.
85. Butt G, Hussain I, Ahmed FJ, Choudhery MS. Efficacy of platelet-rich plasma in androgenetic alopecia patients. J Cosmet Dermatol. 2019;18:996–1001.
86. Zhu JT, Xuan M, Zhang YN, et al. The efficacy of autologous platelet-rich plasma combined with erbium fractional laser therapy for facial acne scars or acne. Mol Med Rep. 2013;8:233–237.
87. Shin MK, Lee JH, Lee SJ, Kim NI. Platelet-rich plasma combined with fractional laser therapy for skin rejuvenation. Dermatol Surg. 2012;38:623–630.
88. Hui Q, Chang P, Guo B, Zhang Y, Tao K. The clinical efficacy of autologous platelet-rich plasma combined with ultra-pulsed fractional CO2 laser therapy for facial rejuvenation. Rejuvenation Res. 2017;20:25–31.
89. Cai J, Tian J, Chen K, Cheng LHH, 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.
90. Kar BR, Raj C. Fractional CO2 laser vs fractional CO2 with topical platelet-rich plasma in the treatment of acne scars: A split-face comparison trial. J Cutan Aesthet Surg. 2017;10:136–144.
91. Min S, Yoon JY, Park SY, Moon J, Kwon HH, Suh DH. Combination of platelet rich plasma in fractional carbon dioxide laser treatment increased clinical efficacy of for acne scar by enhancement of collagen production and modulation of laser-induced inflammation. Lasers Surg Med. 2018;50:302–310.
92. Galal O, Tawfik AA, Abdalla N, Soliman M. Fractional CO2 laser versus combined platelet-rich plasma and fractional CO2 laser in treatment of acne scars: Image analysis system evaluation. J Cosmet Dermatol. 2019;18:1665–1671.
93. Sasaki GH. A preliminary clinical trial comparing split treatments to the face and hand with autologous fat grafting and platelet-rich plasma (PRP): A 3D, IRB-approved study. Aesthet Surg J. 2019;39:675–686.
94. Modarressi A. Platelet rich plasma (PRP) improves fat grafting outcomes. World J Plast Surg. 2013;2:6–13.
95. Zimmermann R, Arnold D, Strasser E, et al. Sample preparation technique and white cell content influence the detectable levels of growth factors in platelet concentrates. Vox Sang. 2003;85:283–289.
96. Rophael JA, Craft RO, Palmer JA, et al. Angiogenic growth factor synergism in a murine tissue engineering model of angiogenesis and adipogenesis. Am J Pathol. 2007;171:2048–2057.
97. Atashi F, André-Lévigne D, Colin DJ, Germain S, Pittet-Cuénod B, Modarressi A. Does non-activated platelet-rich plasma (PRP) enhance fat graft outcome? An assessment with 3D CT-scan in mice. J Plast Reconstr Aesthet Surg. 2019;72:669–675.
98. Lei X, Liu H, Pang M, Zheng Z, Tan X, Cheng B. Effects of platelet-rich plasma on fat and nanofat survival: An experimental study on mice. Aesthetic Plast Surg. 2019;43:1085–1094.
99. Serra-Mestre JM, Serra-Renom JM, Martinez L, Almadori A, D’Andrea F. Platelet-rich plasma mixed-fat grafting: A reasonable prosurvival strategy for fat grafts? Aesthetic Plast Surg. 2014;38:1041–1049.
100. Gentile P, Di Pasquali C, Bocchini I, et al. Breast reconstruction with autologous fat graft mixed with platelet-rich plasma. Surg Innov. 2013;20:370–376.
101. Luck J, Smith OJ, Mosahebi A. A systematic review of autologous platelet-rich plasma and fat graft preparation methods. Plast Reconstr Surg Glob Open. 2017;5:e1596.
102. Xiong BJ, Tan QW, Chen YJ, et al. The effects of platelet-rich plasma and adipose-derived stem cells on neovascularization and fat graft survival. Aesthetic Plast Surg. 2018;42:1–8.
103. Cervelli V, Palla L, Pascali M, De Angelis B, Curcio BC, Gentile P. Autologous platelet-rich plasma mixed with purified fat graft in aesthetic plastic surgery. Aesthetic Plast Surg. 2009;33:716–721.
104. Fontdevila J, Guisantes E, Martínez E, Prades E, Berenguer J. Double-blind clinical trial to compare autologous fat grafts versus autologous fat grafts with PDGF: No effect of PDGF. Plast Reconstr Surg. 2014;134:219e–230e.
105. Choi J, Minn KW, Chang H. The efficacy and safety of platelet-rich plasma and adipose-derived stem cells: An update. Arch Plast Surg. 2012;39:585–592.
106. Tian J, Lei XX, Xuan L, Tang JB, Cheng B. Application of plasma-combined regeneration technology in managing facial acne scars. J Cosmet Laser Ther. 2019;21:138–144.
107. Uysal CA, Ertas NM. Platelet-rich plasma increases pigmentation. J Craniofac Surg. 2017;28:e793.
108. Elnehrawy NY, Ibrahim ZA, Eltoukhy AM, Nagy HM. 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.
109. Lee ZH, Sinno S, Poudrier G, et al. Platelet rich plasma for photodamaged skin: A pilot study. J Cosmet Dermatol. 2019;18:77–83.
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