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]
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.
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.]
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.[73,80,81] Table 4 summarizes available studies using platelet-rich plasma to treat alopecia.
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]
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.
Plast Reconstr Surg. 2021;147(1):219-230. © 2021 Lippincott Williams & Wilkins
