Abstract
Background:
The regenerative properties of platelet growth factors make platelet-rich-plasma (PRP) an attractive modality for treatment of aging skin. The main objective of this study was to determine efficacy and safety of PRP injections and microneedling compared with saline injections in women with aging skin of the face.
Methods:
In this prospective, randomized clinical trial, 18 women with facial aging were randomized to receive either PRP injections to the unilateral face and saline injections to the contralateral side, or vice versa. Microneedling was performed after injections on the entire face. Physician assessment, photographs, and treatment satisfaction questionnaires were used for outcome assessment at baseline and 16- and 24-week follow-ups.
Results:
There was no evidence of improvement and suggestion of worsening in skin laxity and rhytides from baseline to weeks 4, 16, and 24 for PRP and saline (all P ≤ 0.004) and no notable difference in skin roughness between baseline and follow-up time points for PRP or saline (all P ≥ 0.19). The degree of change in skin laxity, rhytides, and skin roughness from baseline to follow-up time points was similar for PRP and saline. All patients experienced some degree of pain/discomfort and burning/stinging sensation at treatment weeks 4, 8, and 12 for both saline and PRP.
Conclusions:
PRP injections did not seem to be effective for treatment of aging skin of the face in women, with no notable macroscopic improvement in appearance when compared with baseline or saline injections. Advanced age of study participants (>45 years) and less-sensitive methods of evaluation may be potential contributing factors to the lack of detected response.
Takeaways
Question: Platelet-rich-plasma (PRP) has been largely used as a treatment modality for facial rejuvenation. The study aimed at assessing the effects of PRP and microneedling on aging facial skin.
Findings: This prospective randomized clinical trial showed no evidence of improvement in skin laxity and rhytides after treatment with injectable PRP and no notable difference in skin roughness between PRP and saline.
Meaning: PRP injections were not effective for treatment of facial skin aging in women aged 45 years and older, with no notable improvement in skin appearance compared with baseline or to saline injections.
INTRODUCTION
Skin aging is characterized by various clinical and histological changes. The most common signs of aging include but are not limited to, fine lines, wrinkles, altered skin texture, and loss of subcutaneous fat around the mouth and temples. Histological changes include flattening of the dermal-epidermal junction, decreased epithelial cell turnover, progressive disappearance of elastic tissue, decrease in collagen fibers, and loss of fibroblasts.1,2 In recent years, there has been an increased interest in treatments focused on improvement of skin appearance. In the cosmetic field, most rejuvenating procedures are easily accessible and quick, with minimal side effects and downtime.3 Current therapies available for aesthetic facial rejuvenation approved by the Food and Drug Administration include topical antiaging products such as tretinoin, microdermabrasion, chemical peels, laser therapy, intense pulsed light, botulinum toxin, and filler injections.4
Microneedling is a minimally invasive skin-rejuvenating procedure in which fine needles create micropunctures in the skin and promote tissue regeneration. These microscopic injuries induce release of growth factors and cytokines, and may result in increased collagen and elastin deposition, and dermal remodeling.5–7 The goal of microneedling is to improve overall skin texture and appearance. It can be used to treat acne scarring, fine lines, wrinkles, skin texture, pore size, and pigmentary disorders.
Platelet-rich-plasma (PRP) is an autologous concentration of human platelets in a small volume of plasma that has a four to seven times higher platelet concentration than baseline.8,9 Activated platelets secrete several cytokines and growth factors, which are believed to promote upregulation of genes responsible for tissue repair, cellular proliferation, angiogenesis, and extracellular matrix synthesis. This may represent an attractive option to promote collagen regeneration in the aging skin, potentially leading to overall improvement of skin appearance.6
Recent investigators have explored the use of PRP as a treatment modality in the aesthetic and rejuvenation field, with available studies to date showing positive results.7,10–12 In a randomized clinical trial, Alam et al studied the effects of PRP on facial skin and found significant improvement in skin texture.10 We further explore this premise in our study. A recent review on the available literature regarding PRP treatment for cosmetic indications identified 22 articles describing the use of PRP, 14 of which were used on the face. Even though all studies reported beneficial effects of PRP on facial skin, indicating a positive response to treatment, only a minority of these were controlled trials. The predominant criticisms of trials to date are the lack of a consensus protocol regarding the exact concentration, dosing parameters, depth of injections, and required frequency of sessions.7 Furthermore, the scarcity of studies using split-face comparisons as controls was also emphasized. The use of split-side studies would allow each subject to serve as their own control, minimizing intersubject variability and enabling a better assessment of the efficacy of PRP treatments. Nonetheless, PRP seems to be a useful tool for treatment of skin aging, and there is a need for randomized controlled studies with reproducible protocols to better study clinical efficacy.
The objective of this randomized, single-blinded study was to assess the effects of PRP and microneedling on aging facial skin.
METHODS
Study Subjects
Eighteen women seen at the dermatology department at Mayo Clinic in Jacksonville, Florida between July 2019 and December 2020 were included in this prospective, randomized, single-blinded study. Patients’ median age was 59 years (range: 47–72 years), all patients were women, and had signs of facial skin aging (wrinkles, skin atrophy, and laxity). Information was collected regarding baseline patient characteristics (demographics, medical history, medications, contraceptive measures, and previous treatments for skin rejuvenation). The most common previous treatments for skin rejuvenation were topical retinoids (77.8%), followed by neuromodulators (50.0%) and injectable fillers (44.4%). Patients were randomized to receive either PRP on the right side of their face and saline on the left side, or saline on the right side and PRP on the left side of their face. Exclusion criteria included the following: abnormal platelet count, serum chemistry, or screening laboratory results; patients who had had any cosmetic procedures for facial skin aging 3 months before enrollment; patients who had had facial resurfacing laser 1 year before enrollment; pregnant or lactating women; patients with infectious diseases, uncontrolled diabetes, history of keloid, active skin disease or skin infection on the intended treatment areas; patients on anticoagulant or antiaggregating therapy; and patients participating in a study of an experimental drug or medical device within 30 days of study entry. During the study, patients were not allowed to make any changes to their routine skin care habits; on the contrary, all facial skin care products were strictly standardized, including facial wash and sunscreen, and no retinoid-containing products were allowed during the entire duration of the study.
Methods
PRP was prepared using a standard benchtop centrifuge, as described below. For PRP preparation, 60 mL of blood was collected from a peripheral vein using a standard venipuncture technique and combined with 8 mL of citrate dextrose solution A as an anticoagulant. Blood was processed using standard dual spin centrifugation. Spin protocol included an initial 10-minute centrifugation (1500 rpm) followed by the removal of the red cell layer. An additional centrifugation at 3500 rpm for 10 minutes was performed (G force of 684 and radius of 50) followed by the removal of 5 mL of platelet-poor plasma with an 18-gauge blunt-tipped aspirating needle, resulting in 5 mL of PRP, which was transferred to five 1-mL sterile syringes. One million platelets per microliter was established as the preferred platelet dose in our PRP preparations. Using a 30-gauge needle, PRP or saline was injected into the malar area in 0.05 mL aliquots, for a total of 20 injection points about 0.5 cm apart. The nasolabial/ melolabial fold areas and periorbital areas were injected in a similar manner, with approximately 10 injection points in each area, with a total volume of 2.0 mL. Using a 25-gauge 38-mm cannula, PRP or saline was injected into the nasolabial folds, periorbital and tear trough areas (1.0 mL per injection point) with a total volume of approximately 2.0 mL. PRP or saline application was followed by microneedling. Microneedling was performed using an Food and Drug Administration–approved device (Skin Pen by Bellus Medical) containing 36 needles of 0.3-mm diameter. The patient’s face was divided into four quadrants, and microneedling was performed six times in four different directions perpendicular and diagonal to each other in a to-and-fro motion. Immediately afterward, the half of the face that received PRP was draped by a thin gauze-sponge soaked with Platelet-poor plasma from the residual PRP, placed on the face for 15 minutes, as an additional topically applied element of the plasma therapy. The saline half-face was draped using saline-soaked gauze that remained on the face for 15 minutes. Water and glycerin-based rescue gel (SkinFuse by Bellus) was used after the procedure, and patients were instructed to avoid chemical sunscreens on the treated areas.
Clinical skin examination information (skin roughness, skin laxity, and rhytids) was collected at baseline and weeks 4, 16, and 24; treatment satisfaction questionnaire at weeks 16 and 24; clinical assessment of injection sites at weeks 4, 5, 8, and 12; patients’ impressions during injections at weeks 4, 8, and 12, and patients’ impressions during microneedling at weeks 4, 8, and 12. Outcomes were assessed through a clinical skin examination using two grading scales, the Allergan Skin Roughness Scale, and the Wrinkle Severity Rating Scale at baseline and weeks 4, 16, and 24. Clinical photographs were obtained at the same time points, and a treatment satisfaction questionnaire was used at weeks 16 and 24. All post week-4 missing data were imputed using the last observation carried forward method.
Statistical Analysis
Continuous variables were summarized with the sample median and range. Categorical variables were summarized with number and percentage of patients. Comparisons of outcomes between baseline and follow-up visits within the separate PRP and saline treatment groups were made using a paired Wilcoxon signed rank test. Comparisons of outcomes between PRP and saline treatments were made using a paired Wilcoxon signed rank test (continuous outcomes) or a paired McNemar test (categorical outcomes). P values of less than 0.05 were considered as statistically significant, and all statistical tests were two-sided. Statistical analysis was performed using R Statistical Software (version 4.0.3; R Foundation for Statistical Computing, Vienna, Austria).
RESULTS
Baseline patient characteristics are shown in Table 1. Table 2 compares skin roughness, skin laxity, and rhytids between PRP and saline through a clinical skin examination assessment. There was no evidence of improvement and interestingly, with a suggestion of slight worsening in skin laxity from baseline to weeks 4, 16, and 24 for both saline and PRP (all P ≤ 0.004), with no difference noted between saline and PRP (all P = 1.00). Similarly, there was no evidence of improvement and a suggestion of slight worsening in rhytids from baseline to weeks 16 and 24 for both saline and PRP (all P ≤ 0.040), as noted in Figures 1 and 2, with similar but not quite significant trends at week 4 (P = 0.095 and 0.065, respectively). The degree of worsening in rhytids from baseline did not differ between PRP and saline (all P ≥ 0.18). There was not a notable difference in skin roughness between baseline and follow-up time points for either PRP or saline (all P ≥ 0.19), with a similar degree of change between the two treatments (all P ≥ 0.081).
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