Efficacy and Safety of Platelet-Rich Plasma and Hyaluronic Acid Combination Treatment for Neck Rejuvenation in Thailand: A Prospective Study

Abstract

Introduction

Combined platelet-rich plasma and hyaluronic acid (PRP-HA) offers a promising nonsurgical technique for tissue regeneration through synergistic efficacy and longevity effects. This study aims to investigate PRP-HA’s efficacy and safety for neck rejuvenation.

Methods

This 32-week prospective trial enrolled 30 Thai participants with mild-to-moderate neck aging. Treatment consisted of three monthly intradermal PRP-HA injections to the anterior neck surface, with follow-ups at 2 weeks, and 1, 2, 3, and 6 months posttreatment completion. Assessment included skin firmness, elasticity, biometric parameters, pain scores, and adverse effects.

Results

Of 29 completing participants, neck skin firmness improved 54% from baseline at 3-month posttreatment completion, increasing to 65% at 6 months (p < 0.0001). While gross elasticity initially improved at 1 month posttreatment (p = 0.0217); it subsequently declined. The 6-month follow-up showed substantial reductions in melanin and erythema (p < 0.01). Sustained improvements were observed in hydration through study completion (p < 0.01). Sebum levels decreased significantly after the first two treatments and at 3 months posttreatment (p < 0.05). No significant changes appeared in skin texture, wrinkles, and brightness. Most participants reported 51–75% improvement after the third treatment, maintaining through 6 months. No severe adverse effects were reported.

Conclusions

PRP-HA demonstrates safe and effective improvements in neck skin firmness, hydration, and pigment and sebum regulation, with benefits lasting 6 months after three treatment sessions. However, variable effects on elasticity and modest results on wrinkles, texture, and brightness warrant further controlled trials to further elucidate and confirm its rejuvenative properties on the neck.

Trial Registration

This trial is registered under the Thai Clinical Trials Registry (TCTR20230212003).

Key Summary Points

Why carry out this study?

Neck aging is a growing aesthetic concern, yet effective, long-lasting nonsurgical treatment options remain limited. PRP-HA offers a potential solution given its synergistic regenerative properties.

The objective of this study was to evaluate the safety and efficacy of three monthly intradermal PRP-HA injections for neck rejuvenation in adults with mild-to-moderate neck aging.

What was learned from the study?

Significant improvements were observed in skin firmness (up to 65% at 6 months), hydration, and reductions in melanin, erythema, and sebum, with no severe adverse effects reported. Outcomes on skin elasticity, wrinkles, texture, and brightness were modest.

These findings suggest PRP-HA as a relatively safe and viable minimally invasive treatment for neck rejuvenation; albeit, variable results on certain biometric parameters highlight the need for further controlled studies.

Introduction

The neck undergoes various skin transformations as it matures. Often described as the “tell-tale sign” of aging, it is frequently overlooked in cosmetic considerations by both participants and physicians. Horizontal neck lines, laxity, prominent platysmal bands, diminished mandibular contour, submental fat buildup, and dyspigmentation all contribute their wizened appearance [1]. Unlike age-related facial wrinkles, neck wrinkles may appear in younger years. The constant neck bending while using mobile devices, further exacerbated by involutional skin laxity is a factor contributing to their prevalence [2]. In addition to environmental factors, racial demographics are also important, since aging necks in Asians and Caucasians differ in aspects such as thickness and fat accumulation patterns [3].

Currently, several treatment options are available that target the different problem areas of the neck. Nonsurgical options have grown tremendously in recent years, revolutionizing the approach to neck rejuvenation. The appeal of these treatments is in their minimal downtime, lower risk profile, and relatively lower cost than undergoing a more drastic surgical intervention. Moreover, today’s participants are making more informed choices and are now also seeking “pre-juvenation,” which is ideally suited for minimally invasive therapies [4, 5].

Recent research has explored the synergistic effects of both platelet-rich plasma (PRP) and hyaluronic acid (HA) for facial skin rejuvenation and their enhanced anabolic function of dermal fibroblasts. In addition to their individual benefits, HA and autologous PRP have been shown to play key roles in tissue regeneration by stimulating cell signaling at the injection site. The addition of HA to PRP is thought to allow the influx of growth factors released by PRP to be trapped, and therefore prolong the activation of the synthesis of collagen and other matrix components by stimulating the activation of fibroblasts, ultimately promoting skin rejuvenation [6].

There is still a paucity of robust trials on this combination treatment for skin regeneration. Moreover, studies specifically targeting the neck for this indication have yet to be published. If proven effective and safe, this technology can be harnessed not only for the face and neck, but also for other areas, such as the décolletage and hands. The main objective of the study is to evaluate the efficacy and safety of PRP-HA for neck rejuvenation among participants of Thai descent.

Methods

Study Design and Ethical Considerations

This single-arm prospective interventional study involved 30 Thai adults who received three monthly combination treatments of PRP-HA on the anterior neck. The study was conducted at the Dermatology Department of Siriraj Hospital, Bangkok, Thailand from December 2022 to September 2023. The protocol was approved by the Siriraj Institutional Review Board (COA no. Si 780/2022 Faculty of Medicine, Mahidol University), and conducted in accordance with the guidelines of the Declaration of Helsinki (Clinical Trial Registration: TCTR20230212003, www.clinicaltrials.in.th). All participants were provided with detailed information on the Institutional Review Board (IRB)-approved study protocol. Informed consent was obtained prior to enrollment, which encompassed publication of data and images from the trial.

Participants

Participants were directly recruited from the Siriraj Skin Laser Center and Dermatology Outpatient Department of Siriraj Hospital, Bangkok, Thailand. Investigators assessed each participant’s eligibility on the basis of the following criteria. Eligible participants included male and female adults 18–60 years with neck laxity ranging from 1 to 5 on the Wrinkle Assessment Scale for horizontal neck folds [7]. Exclusion criteria comprised pregnant or lactating women; acute neck infection and/or dermatitis; coagulopathy; platelet dysfunction; thrombocytopenia; cancer; and liver pathology, autoimmune disease, or any condition that might interfere with the results. Additionally, participants with known hypersensitivity to any of the interventional components, history of keloid formation, and recent neck treatments (e.g., lasers, energy-based devices, neurotoxins, and/or fillers) within the past 6 months, as well as regular use of exogenous hormones, nonsteroidal anti-inflammatory drugs, dietary supplements, or medications that affect platelet function were excluded.

Preparation of PRP-HA Mixture

Cellular Matrix^® (Regen Lab SA, Le Mont sur Lausanne, Switzerland) was used for this study (Fig. 1) [8]. The kit included the Blood Cell Therapy with HA (BCT-HA) tube, which facilitated the preparation of approximately 4 mL of PRP-HA (2 mL of PRP combined with 2 mL of HA). Each BCT-HA tube contained: 2 mL of non-crosslinked HA gel (20 mg/mL, 40 mg per tube; 1550 kDa HA obtained from bacterial fermentation) in a phosphate buffer (composed of sodium chloride, dipotassium hydrogen phosphate, potassium dihydrogen phosphate, potassium chloride, and water for injection); 3 g of inert cell-selector gel; and 0.6 mL of 4% sodium citrate as liquid anticoagulant (Fig. 1A). Using proper aseptic technique, 4 mL of whole blood was collected via venipuncture. This procedure was expected to yield 70% platelet recovery, with an average platelet concentration of 340–400 million platelets/mL, as well as 94.3% granulocyte depletion and 99.5% red blood cell depletion [9]. The BCT-HA tube containing whole blood was centrifuged at 1500g for 5 min using the Regen Lab centrifuge (Fig. 1B). Following centrifugation, the blood was fractionated into red blood cells trapped beneath the separator gel, cellular elements remaining on its surface, and HA layered over the plasma (Fig. 1C). The tube was inverted vertically until the HA detached from the tube walls and floated on top of the plasma layer. To ensure a homogeneous mixture, the tube was inverted 20 times to fully resuspend the platelets (Fig. 1D). Finally, using the provided transfer device, 2 mL of PRP-HA mixture was collected into two 1 mL syringes, ready for use.

Fig. 1.

PRP-HA preparation using the Cellular Matrix^® Regen Lab protocol. PRP-HA platelet-rich plasma and hyaluronic acid

Intervention Protocol

Topical anesthetic cream containing 2.5% lidocaine and 2.5% prilocaine (EMLA™ cream 5%, AstraZeneca, Wilmington, USA) was applied to the anterior neck of each participant under occlusion for 45–60 minutes  prior to each treatment. After removing the cream with a clean gauze, the treatment area was disinfected with chlorhexidine solution. Using a 1 mL syringe fitted with a 30-gauge, 1.5 inch needle, 0.1 mL of PRP-HA was injected intradermally into the anterior neck at 0.5 cm intervals along the horizontal neck lines, covering an area of approximately 0.25 cm² per injection site. Any excess solution was administered between the neck lines. Each participant received 2 mL of PRP-HA per session, with three treatments administered at 1-month intervals. Following the three treatment sessions, participants were evaluated at 2 weeks and 1, 2, 3, and 6 months after the final treatment.

Objective Evaluation: Biometric Skin Analysis

Primary outcome measures in the study were mean changes in neck skin firmness (R0) and gross elasticity (R2), as measured by the Cutometer^® dual MPA 580 (Courage + Khazaka, Cologne, Germany). Secondary endpoints included average differences in in vivo skin quality—specifically, skin texture and wrinkles measured with the Antera 3D^® (Miravex, Dublin, Ireland), and melanin, erythema, moisture, brightness, and oil levels measured with the Mexameter^® MX 18, Corneometer^® CM 825, Colorimeter^® CL400, and Sebumeter^® (Courage + Khazaka), respectively. Uniformity was ensured by using the same biometric parameters. All measurements were taken 2 cm lateral to the hyoid cartilage, on both the left and right sides, while the neck was hyperextended and were performed at baseline, 1 month after the first and second treatments, and at 2 weeks and 1, 2, 3, and 6 months after the third treatment.

Subjective Evaluation: Clinical and Participant Evaluations

Photography was standardized using a PowerShot G9 (Canon, Tokyo, Japan) camera at baseline, and before injection during every treatment and follow-up visit. To ensure consistency, lighting, camera settings, and neck positioning were standardized across all visits. Subjects were asked to be in the same partial chin-up position, with a 120° angle between the chin and neck. Clinical assessments were conducted by participants and two blinded dermatologists, who evaluated comparative photographs using a quartile grading scale (Table 1). Pain scores were recorded after each treatment session using a visual analog scale, with 0 indicating no pain and 10 representing the worst pain.

Table 1.

Quartile-based grading scale for improvement

Scale	Percentage of improvement	Description
0	0%	No improvement
1	1–25%	Slight improvement
2	26–50%	Moderate improvement
3	51–75%	Good improvement
4	76–100%	Excellent improvement

Treatment response was graded on a 5-point scale

Adverse Event Monitoring

All adverse effects, including bruising, erythema, edema, irritation, dermatitis, dyspigmentation, oozing, crusting, infection, lumps, or scars, were recorded and managed appropriately.

Statistical Methods

Descriptive analyses were performed using means and standard deviations, while qualitative data were summarized as percentages and frequencies. The means of the outcome variables were calculated and compared using repeated measures analysis of variance (ANOVA) to assess the differences between baseline and posttreatment measurements. An intention-to-treat analysis was conducted, and results with p values < 0.05 were considered statistically significant. All statistical analyses were performed using SPSS Statistics for Windows (Version 26.0, IBM Corp., Armonk, United States) and Prism (Version 9.2, GraphPad, Boston, United States).

Results

Participant Characteristics

A total of 30 participants aged between 35 and 59 years (mean age 46.4 ± 5.7 years) were included in the study. Of these, 60% were aged 40–49 years, while 40% were aged 50–59 years, and 27 (90%) were female. Fitzpatrick skin types were either IV (90%) or V (10%) (Table 2). In total, 29 (96.7%) completed the 6-month follow-up and were included in the data analysis. No participants withdrew because of adverse events from the intervention.

Table 2.

Patient demographics

	Total (n = 30)
Age (years)
Mean ± SD	46.4 ± 5.7
Range	35–59
Age distribution (years); n (%)
30–39	3 (10.0)
40–49	18 (60.0)
50–59	9 (30.0)
Sex; n (%)
Female	27 (90.0)
Male	3 (10.0)
Fitzpatrick skin type; n (%)
IV	27 (90.0)
V	3 (10.0)

Data are presented as mean ± SD and range, or n (%), as appropriate

SD standard deviation

Neck Skin Firmness and Elasticity

The Cutometer^® measures the indirect relationship of R0 to skin firmness, where a rise in R0 corresponds to a decline in skin firmness. This trial reported a decrease in skin firmness from baseline (0.26 ± 0.08) shortly after receiving treatment. Mean R0 increased significantly after the first (0.45 ± 0.09, p < 0.0001) and second (0.37 ± 0.09, p < 0.0001) PRP-HA administrations. R0 continued to remain significantly elevated above the baseline after 2-week (0.32 ± 0.10, p = 0.0012) and 4-week (0.43 ± 0.11, p < 0.0001) posttreatment completion. However, skin firmness substantially improved thereafter. A 54% and 65% R0 drop was seen after 3-month (0.12 ± 0.07, p < 0.0001) and 6-month (0.09 ± 0.05, p < 0.0001) follow-up posttreatment completion (Fig. 2A).

Fig. 2.

Mean differences in neck bioparameters over time. Panels depict changes in neck bioparameters across study timepoints: (a) firmness (R0), (b) gross elasticity (R2), (c) melanin index, (d) erythema index, (e) hydration, and (f) sebum levels. Statistical significance is denoted as *p < 0.05, **p < 0.01, ***p < 0.001, ***p < 0.0001. AU arbitrary units, BL baseline, T1 (1 MO) 1 month post-first treatment, T2 (1 MO) 1 month post-second treatment, T3 (2 WK) 2 weeks post-third treatment, T3 (1 MO) 1 month post-third treatment, T3 (2 MO) 2 months post-third treatment, T3 (3 MO) 3 months post-third treatment, T3 (6 MO) 6 months post-third treatment

Additionally, the three PRP-HA treatments significantly improved baseline gross neck elasticity, as measured by R2. Elasticity was documented to have increased by 8% after 1 month (83.25 ± 10.51, p = 0.0217) posttreatment. However, R2 declined significantly by 3-month posttreatment completion (60.88 ± 19.86, p = 0.0011), and further in the sixth (35.35 ± 24.14, p < 0.0001); this decline extended until the end of the protocol (Fig. 2B).

Pigmentation, Texture, and Wrinkles Changes

Pigmentation measurements revealed one significant reduction in mean melanin index from baseline (198.80 ± 86.93). Pigmentation had decreased after 6 months (to 170.40 ± 53.08, p = 0.0069) post-final PRP-HA injection (Fig. 2C). Similarly, erythema index decreased from baseline (270.20 ± 109.90). After treatment completion, significant results were seen at 2 months (230.30 ± 63.26, p = 0.0313) and 6 months (225.00 ± 61.32, p = 0.0061) after all treatments (Fig. 2D).

The Antera 3D^® results demonstrated no significant changes in skin texture and wrinkles compared with baseline following treatment intervention. Although trends showed a slight improvement, these differences were not statistically significant. Neck skin brightness also reported no statistically significant improvements when measured with the Colorimeter^®. Although skin brightness was slightly elevated, these changes were only noted 1 month after the second treatment administration, and 2 weeks after the final administration.

Skin Hydration and Sebum Reduction

Skin hydration was significantly impacted by PRP-HA treatments. A 14% increase from baseline (52.05 ± 10.21) was reported 2 weeks (59.32 ± 13.76, p = 0.0003) after receiving all administration. Peak mean moisture index was reported for an 18.5% increase in skin hydration after 2 months (61.72 ± 13.98, p < 0.0001) upon receiving the final treatment. This significant increase in moisture persisted in the following 3 months (p = 0.0131) and 6 months (p = 0.0015) (Fig. 2E).

Significant decreases in sebum levels were observed after the first (15.67 ± 14.63, p < 0.0001) and second (16.71 ± 14.56, p = 0.0009) PRP-HA injections, compared with baseline (28.90 ± 22.71). These values corresponded to the distinct 45.78% and 42.18% reduction, respectively. Although sebum level reductions persisted, these levels were less pronounced. However, a subsequent significant decrease was reported at 3-month (19.71 ± 19.61, p = 0.0145) posttreatment completion (Fig. 2F).

Participant and Physician Assessment

After the first PRP-HA treatment, participants reported a mean assessment score of 24.48 ± 27.85%, with 13 (45%) participants showing no improvement, and 8 (28%) noting a 26–50% improvement. One month following the second treatment, the mean score increased to 41.72 ± 29.44, with nine (31%) and seven (24%) participants showing moderate (26–50%) and good (51–75%) improvement, respectively. At 2 and 4 weeks following the last PRP-HA administration, nine (31%) participants reported 51–75% improvement, making up the majority of patients at these timepoints. By the second-month follow-up, seven (24%) participants reported at least a 76% improvement, while ten (34%) noted 51–75% better outcomes. Peak neck rejuvenation was reported at 3-month posttreatment completion, with a mean improvement score of 54.24 ± 27.14–28%. At this timepoint, eight (28%) participants experienced 76–100% improvement, while the majority of participants (31%) observed a 51–75% overall enhancement of the neck. These benefits were perceived to have persisted until protocol completion, with a mean improvement score of 51.90 ± 27.88%, with 18 (52%) participants showing good-to-excellent improvement (Figs. 3A, 4).

Fig. 3.

Quartile treatment improvement scale. Panels represent treatment improvement scores for (a) participants and (b) physicians, graded on a 5-point, color-coded scale. Legend: 0, white = no improvement (0%); 1, yellow = slight improvement (1–25%); 2, orange = moderate improvement (26–50%); 3, green = good improvement (51–75%); 4, blue = excellent improvement (76–100%). PRP-HA platelet-rich plasma and hyaluronic acid

Fig. 4.

Representative case of PRP-HA treatment over time. Images of a 43-year-old female pre- and post-PRP-HA treatment, showing overall moderate improvement after three treatment sessions with effects sustained up to 6 months. Panels: (a) Baseline, (b) 1 month after first PRP-HA, (c) 1 month after second PRP-HA, (d) 2 weeks after third PRP-HA, (e) 1 month after third PRP-HA, (f) 2 months after third PRP-HA, (g) 3 months after third PRP-HA, and (h) 6 months after third PRP-HA. PRP-HA platelet-rich plasma and hyaluronic acid

Dermatologists’ evaluation indicated that at each timepoint, 45–69% of participants exhibited 1–25% improvement across the study period. After the initial PRP-HA injection, 10 (34%) participants exhibited 26–50% improvement, while 16 (55%) others reported 1–25% improvement. After the second, 6 (21%) participants showed moderate improvements, while 17 (59%) had slight improvement. One month post-final treatment, nine (31%) participants showed 26–50% improvements, while 16 (55%) were reported to have improved ≤ 25%. Effects on overall neck rejuvenation persisted through study completion, with 55% of participants exhibiting slight-to-moderate (1–50%) improvements (Figs. 3B, 4).

Pain and Adverse Events

Treatment-related pain averaged 3.68 ± 2.07 (absence of pain = 0, severe pain = 8), corresponding to mild-to-moderate pain levels. No severe adverse effects were observed. Additionally, participants denied any common complications (e.g., hematomas, ecchymosis, bruising, prolonged and excessive swelling and tenderness, infections, hypersensitivity reactions, nodules, skin necrosis, unwanted lumps, or Tyndall effect).

Discussion

Mechanism of Action

Most skin-tightening treatments for the neck induce wound healing through mechanical, thermal, or chemical trauma. During the final stage of wound healing, collagen realignment and contraction produces skin-tightening effects. However, patients with significant skin laxity, sun damage, or advanced age may see reduced effectiveness from these approaches [10]. In recent years, PRP has gained significant attention for its role in wound healing and dermal remodeling. Its therapeutic potential has been validated through high-quality meta-analyses, systematic reviews, and randomized controlled trials in the fields of cardiology, plastic surgery, orthopedic surgery, pain management, neurology, and dermatology. This has created numerous variations in both its preparation and its use as an adjunctive treatment for skin rejuvenation [11–13]. In skin hydration, HA plays a crucial role. Its levels are regulated by the balance between synthesis and degradation, as well as its interactions with cellular structures. HA has become indispensable in aesthetic medicine due to its role in collagen synthesis and maintenance, combined with its immediate volumizing effects.

Comparison with Existing Treatments

The Cutometer^® measures skin firmness (R0) and elasticity (R2) by applying controlled suction and assessing the resulting deformation. R0 represents firmness, with higher values indicating greater skin distensibility (less firmness). Conversely, R2 measures overall elasticity, with higher values indicating an improved capacity to recover from external deformation [14, 15].

This study observed that initial R0 increased upon receiving treatment, indicating a decline in skin firmness. However, after the third administration of PRP-HA, R0 values steadily tapered down, signaling progressive improvements in firmness, which persisted through the 6-month follow-up. HA essentially provides dermal support and hydration, whereas PRP stimulates fibroblasts to produce collagen and extracellular matrix components; thereby increasing firmness through matrix reinforcement and dermal thickening. These results partially aligned with the findings of Hersant et al. on autologous PRP-HA facial rejuvenations, which reported nonsignificant elasticity improvements despite visible skin elasticity rejuvenation [16]. Interestingly, gross elasticity (R2) exhibited a biphasic pattern where it was observed to increase 1 month after treatment, followed by significant reductions at 3 and 6 months. These results align with a study by Cho et al. [17], where fibroblasts demonstrated a peak elastin expression within 24 h-followed by a decline, whereas procollagen levels continued to rise at 48 and 72 h. These seemingly conflicting results between tissue firmness and elasticity may be due to several mechanisms. Firstly, elastic fiber remodeling occurs more slowly than collagen, which may affect elastic recoil and contribute to the observed reduction in R2. Secondly, new collagen may provide increased firmness, but may be more rigid and less organized, limiting the skin’s ability to recoil [18].

These regenerative effects are largely attributed to growth factors within PRP, which plays a critical role in fibroblast proliferation and matrix metalloproteinase (MMP) expression. Platelet-derived growth factor (PDGF) promotes fibroblast development and neocollagenesis, while TGF-β1 augments type 1 collagen synthesis and inhibits degeneration. MMPs facilitate organized extracellular matrix (ECM) remodeling, with histopathologic evidence confirming increased neocollagenesis following PRP treatment [19–22]. The prolonged skin-firming effects observed in this study likely reflect the extended proliferative and remodeling phases of wound healing, where cellular proliferation and ECM maturation occur gradually over several months.

Beyond its regenerative effects, PRP-HA also demonstrated potential in improving hydration, texture, and overall skin quality. While Antera 3D^® analytics did not show significant improvements in skin texture and wrinkles, a slight improvement was noted and maintained through the 1-month follow-up period. The improved response observed in the present study may be partially attributed to HA. While the difference in results did not reach statistical significance, PRP-HA mimics the natural healing by gradually releasing growth factors, which in turn stimulates cell proliferation, differentiation, and the synthesis of collagen and elastin fibers. HA serves as more than just a carrier—it serves as a water-binding scaffold within the ECM, creating optimal environment for growth factor function. By incorporating HA, growth factors released by PRP can be prolonged and ultimately lead to ECM restoration for tissue regeneration [16, 23]. Additionally, some improvements in skin quality may also be attributed to the microwounds caused by the needle injections themselves. While microneedling has been shown to stimulate collagenesis and dermal thickening, studies comparing PRP with saline-injected microtrauma suggested PRP’s significantly greater skin improvements [24], thus reinforcing PRP’s regenerative potential beyond simple mechanical stimulation.

Previous research indicates that wrinkle improvement correlates with treatment frequency, requiring at least six sessions for significant results. PRP-HA shows limited efficacy for deeper horizontal lines, particularly in overweight participants [25], likely due to the skin’s deeper fibromuscular attachment [2]. A related trial of 23 participants receiving three monthly PRP injections showed 28% improvement in horizontal neck bands and 33% improvement in skin homogeneity and texture [26]. The lack of significant improvement in wrinkles observed in this study therefore suggest that PRP-HA may not be best indicated for treatment of deeper neck rhytides, but rather, more suited for enhancing skin quality, hydration, pigmentation, firmness, and early skin laxity.

Age significantly impacts PRP therapy outcomes, with ideal results seen in younger participants with minimal skin laxity and fine wrinkles. Participants under 40 years show greater mean improvement compared with older participants [27], attributed to age-related decline in growth factor receptor expression and fibroblast response [28]. Our study’s predominantly older population (> 40 years) may explain the less-than-ideal results. Nevertheless, the observed neck rejuvenation likely stems from wound healing properties, supporting cell proliferation, neocollagenesis, and ECM restoration [25].

A similar study by Sirithanabadeekul et al. also reported nonsignificant effects on skin pigmentation. Their initial Mexameter^® measurements reported no significant changes in melanin and erythema indices over the first 20 weeks, though both studies observed gradual melanin improvements over time [29]. A notable decrease in melanin emerged 6 months posttreatment, potentially linked to PRP’s melanogenesis inhibition via TGF-β1 PAX3 suppression and EGF’s prostaglandin E2 inhibition [19, 30, 31]. While Colorimeter^® measurements indicated no significant brightness changes, previous studies suggest that PRP may enhance skin radiance through improved microcirculation [16, 20].

PRP-HA significantly enhanced hydration per Corneometer^® measurements, with sustained effects up to 6 months post-treatment. HA directly contributes through its water-binding capacity of 1000 times its volume [32, 33]. Upon injection, HA molecules attract water maintaining a high level of tissue hydration. Additionally, PRP monotherapy has shown hydration improvements 1–3 months posttreatment [24], aligning with Ulusal’s findings on PRP-HA facial rejuvenation [25].

Results also demonstrated a significant decrease in mean sebum levels, with reductions 1 month after the first and second treatment and 3 months after the final treatment. This effect may stem from HA’s role in lipid regulation, as sebaceous glands express with CD44, a surface receptor for HA. Studies by Jung et al. revealed that HA inhibits sebocyte proliferation and lipogenesis, leading to clinically significant reduction in sebum secretion within 2 weeks after HA injection in oily skinned volunteers [34].

Both participant and physician evaluations showed significant improvements from baseline. Peak participant satisfaction occurred 3 months posttreatment with 54.24% improvement, matching previous facial PRP-HA studies [16]. Participants predominantly reported good improvement (51–75%), persisting through the 6-month follow-up. Physicians noted more modest improvements (≤ 25%) but confirmed sustained effects throughout the study period. Differences in subjective assessments between the participants and physicians are common in esthetic interventional studies where physicians rely more on symmetry and structural endpoints; while participants are more sensitive to changes in skin quality such as hydration, brightness, and firmness. This translates to more critical assessments from the physicians’ perspective [35]. Nevertheless, the subjective assessments corroborated the measured biometric parameters.

Common PRP and HA complications include transient injection site pain, erythema, bruising, or hematoma. [19]. Rarer, severe effects can include nodules, granulomas, Tyndall effect, hypersensitivity reactions, infections (e.g., herpes simplex virus, bacterial), vascular occlusions, and tissue necrosis [36]. In this study, participants experienced only mild-to-moderate pain with no severe adverse outcomes, highlighting the treatment’s favorable safety profile.

The present study is not without its limitations. The lack of a control arm, whether in the form of saline injections or microneedling alone, presents a considerable challenge in distinguishing whether the perceived effects were produced by PRP-HA itself or the microtrauma and subsequent wound-healing cascade triggered by the series of injections. Recognized in literature are the modest improvements in skin firmness and texture by needle trauma, through its concerted growth factor release, fibroblast activation, and neocollagenesis [24, 37]. Nevertheless, it is worthy to note that the magnitude and durability of the improvements seen in the present study, which extend over several months, strongly suggest that the outcomes reflect biological activity from PRP-HA, rather than injection-related effects. As such, further studies are warranted to further support these conclusions, employing placebo or split-face designs, with objective outcome measures such as histopathology, biomarkers, or computed tomography to evaluate structural changes. Once these effects are well defined, integrating PRP-HA with other treatment modalities—such as lasers and energy-based devices—its rejuvenating effects could be further enhanced.

A Turkish study previously demonstrated a statistically significant correlation between number of treatment sessions and overall participant satisfaction with a similar PRP-HA combination treatment [25]. Notably, the most significant effects seen in the study were observed at the later stages, extending up to the 6-month posttreatment. It is therefore recommended to further extend the period of study to better determine the longevity of sustained effects of PRP-HA.

This study represents the first of PRP-HA for neck rejuvenation. A key challenge in PRP therapy research remains standardization, complicating conclusive assessments. While initially attributed to varying preparation protocols affecting growth factor quantities, recent evidence suggests interindividual heterogeneity stems from genetic and environmental factors influencing the megakaryocyte [19, 38]. The varied research outcomes reflect the technology’s complexity. Further research is needed to establish its role in cosmetic dermatology, including potential synergies with lasers and energy-based devices.

Conclusions

This study demonstrates that combination of PRP-HA administered intradermally in three monthly doses effectively rejuvenates the neck in Thai participants with mild-to-moderate aging. Cutometer^® results showed a 48% increase in skin firmness 3 months after the final treatment, sustained for 6 months. Gross skin elasticity increased 1 month posttreatment but declined by the third and sixth months. Melanin and erythema indices significantly decreased at 6 months. PRP-HA notably increased skin hydration, peaking at 2 months and lasting 6 months. It also reduced sebum secretion after the first and second sessions 3 months post-treatment. No significant changes were observed in texture, wrinkles, and brightness. Most participants reported 51–75% improvement after the third injection, lasting 6 months; peak results were seen at 3 months. Physician noted modest but sustained improvements.

PRP-HA’s efficacy stems from its synergistic effects. PRP delivers growth factors that stimulate fibroblasts, collagen production, and ECM remodeling. HA enhances this process by hydrating tissue, optimizing growth factor activity, and prolonging collagen synthesis. Together, they reinforce rather than weaken each other, making this an exciting advance in regenerative medicine. No serious adverse effects occurred. Its favorable safety profile, minimal downtime, and sustained effects lasting up to 6 months, render it an attractive minimally invasive treatment option. However, further randomized clinical trials with histopathological and imaging studies are needed to fully establish its effects and its long-term role in anti-aging therapy.

Author Contributions

Stephanie de Leon, Diandra Zabala, Noldtawat Viriyaskultorn, Panyapat Buranaporn, Woramate Bhorntarakcharoen, Thrit Hutachoke, Thanyaporn Leesanguankul, Teerapat Wannawittayapa, Wetch Tantrapongsathorn, Sariya Sittiwanaruk, and Rungsima Wanitphakdeedecha contributed to the study conceptualization, design, and execution. All the authors read and approved the final manuscript.

Funding

This project and the journal’s Rapid Service Fee was funded by a grant from the Faculty of Medicine, Siriraj Hospital, Mahidol University. Medications and equipment were provided by Regen Lab SA, Astraco Medical Networks Limited, Bangkok, Thailand.

Data Availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Declarations

Conflict of Interest

Stephanie de Leon, Diandra Zabala, Noldtawat Viriyaskultorn, Panyapat Buranaporn, Woramate Bhorntarakcharoen, Thrit Hutachoke, Thanyaporn Leesanguankul, Teerapat Wannawittayapa, Wetch Tantrapongsathorn, Sariya Sittiwanaruk, and Rungsima Wanitphakdeedecha declare that they have no competing interests.

Ethical Approval

The protocol was approved by the Siriraj Institutional Review Board (COA no. Si 780/2022 Faculty of Medicine, Mahidol University), and conducted in accordance with the guidelines of the Declaration of Helsinki (Clinical Trial Registration: TCTR20230212003, www.clinicaltrials.in.th). All participants were provided with detailed information on the IRB-approved study protocol. Informed consent was obtained prior to enrollment, which encompassed publication of data and images from the trial.