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Plastic and Reconstructive Surgery Global Open logoLink to Plastic and Reconstructive Surgery Global Open
. 2026 Sep 28;14(9):e8109. doi: 10.1097/GOX.0000000000008109

A Prospective Split-face Trial Evaluating Skin Recovery and Enhancement with Polynucleotide (Rejuran) Following Fractional Needle Radiofrequency Treatment

JongSeo Kim 1,✉
PMCID: PMC13619185  PMID: 42808113

Abstract

Background:

Fractional needle radiofrequency (FN-RF: Sylfirm-X) is a widely used energy-based treatment for skin rejuvenation, but it often disrupts the epidermal barrier and delays recovery. Polynucleotide (PN: Rejuran) injection has emerged as a recovery adjunct to promote post-RF healing. This study evaluates whether PN enhances skin barrier recovery when used immediately after FN-RF.

Methods:

A prospective, split-face clinical trial was conducted in 25 female patients 20–60 years of age. Immediately after treatment, 2 mL of PN was injected into right side, and 2 mL of normal saline was administered to the left side as a control. Skin parameters were objectively measured at baseline and 6 weeks after treatment, including pore size and wrinkle depth in 3-dimensional photography, transepidermal water loss and stratum corneum hydration, cutaneous elasticity, and sonographic dermal thickness. Patient-reported outcomes regarding redness resolution, burning sensation, and perceived improvements in pores, wrinkles, and elasticity were also collected.

Results:

PN-treated sides showed significantly greater improvement in pore score (Δ +4.79 versus +0.95, P < 0.001) and wrinkle score (Δ +5.04 versus +3.67, P < 0.001). Transepidermal water loss decreased significantly only on the PN side (8.19→3.85, P < 0.001), and stratum corneum hydration increased more markedly (23.42→48.19, P < 0.0001). No significant differences were observed in dermal thickness or elasticity. Patient-reported outcomes indicated faster erythema resolution and higher satisfaction on the PN-injected side.

Conclusions:

PN injection following FN-RF treatment significantly accelerates skin recovery, improves hydration, and enhances pore refinement compared to radiofrequency alone. PN serves as a clinically effective adjunctive therapy for optimizing postprocedural outcomes in aesthetic dermatology.


Takeaways.

Question: Can combining needle-type radiofrequency (RF) treatment with injection of polynucleotides (Rejuran) enhance skin hydration, barrier function, and recovery compared to RF alone?

Findings: In this prospective split-face study, 20 patients underwent RF alone on one side and RF + Rejuran on the other. Quantitative analysis using transepidermal water loss, stratum corneum hydration, and skin scores showed significantly improved hydration and barrier function on the RF+PN side. Patient-reported wrinkle, elasticity, and pore scores also favored combination therapy. 3-dimensional topographic imaging revealed more smoothing and pore reduction on the RF+PN side.

Meaning: The combination of needle RF and Rejuran significantly enhances skin hydration and recovery compared to RF alone.

INTRODUCTION

Fractional needle-based radiofrequency (FN-RF) systems have become widely adopted in aesthetic dermatology for their ability to stimulate dermal remodeling through controlled thermal coagulation. These devices effectively target wrinkles, pigmentation, and acne scarring by delivering energy into the reticular dermis, inducing neocollagenesis and tissue tightening. However, the process inherently disrupts the epidermal barrier, often leading to transient erythema, edema, and increased transepidermal water loss (TEWL). Accordingly, optimal postprocedure management is crucial for reducing downtime and promoting rapid recovery.1–6

Polynucleotide (PN) has been shown to activate fibroblast proliferation, upregulate type I collagen synthesis, enhance fibroblast migration, modulate matrix metalloproteinase-1 and matrix metalloproteinase-3 activity, and support microvascular regeneration through nucleotide-mediated adenosine receptor pathway stimulation. PN injections—specifically Rejuran (PN), which consists of purified DNA fragments derived from salmon—have garnered increasing interest as a regenerative agent in postprocedural care. PN has demonstrated multiple biological benefits, including stimulation of fibroblast activity, extracellular matrix synthesis, angiogenesis, and epidermal barrier restoration. Several clinical studies have suggested its efficacy in enhancing skin quality and improving wound healing, but few have rigorously assessed its role as an adjunct following fractional radiofrequency (RF) treatment using objective, biophysical endpoints.7–10

Moreover, anecdotal clinical observations suggest that PN injection may improve not only hydration and skin barrier parameters but also skin texture, such as pore size reduction and fine wrinkle improvement, particularly when administered following energy-based procedures. Nevertheless, there remains a lack of controlled, quantitative data to support these claims.11–18

This prospective, split-face clinical study was designed to objectively evaluate the efficacy of PN injection administered following fractional needle RF treatment. Using standardized biophysical instruments and photographic documentation, we assessed key skin parameters, including TEWL, stratum corneum hydration (SCH), elasticity, pore size, and wrinkle depth. The primary objective was to determine whether adjunctive PN treatment leads to superior epidermal recovery, hydration, and overall skin rejuvenation compared to RF treatment alone.19–23

METHODS

Study Design and Subjects

The primary objective of this study was to evaluate whether PN injection enhances post–FN-RF recovery—specifically epidermal barrier restoration and hydration—compared with FN-RF alone. This was a prospective, single-center, split-face clinical trial involving 25 healthy female patients 20–60 years of age who presented with facial wrinkles, dryness, and mild-to-moderate skin laxity. Exclusion criteria included active dermatitis, keloid tendency, pregnancy, and hypersensitivity to PN. None had received fillers, botulinum toxin, or energy-based treatments in the prior 6 months. All participants provided written informed consent. The protocol was approved by the public institutional review board, Ministry of Health and Welfare, Republic of Korea (institutional review board no. P01-202411-06-002). All participants provided written informed consent after being fully informed about the split-face design, the application of different treatments on each side, and the possibility of temporary asymmetry or differential recovery. The study was conducted in accordance with the Declaration of Helsinki.

Each subject received bilateral full-face FN-RF treatment using the Sylfirm-X system (VIOL Co., Gyeonggi-do, Republic of Korea). The first pass was performed uniformly with the following parameters: interval of 0.1 seconds, depth of 1.5 mm, power level 8, and 300–350 shots. A second pass was applied to areas with less erythema using intervals of 0.1 seconds, depth of 0.5 mm, power level 5, and 100–150 shots. Immediately after FN-RF, the right hemiface received 2 mL of PN (Rejuran, PharmaResearch Co., Republic of Korea) via 25G cannula, whereas the left hemiface served as control and received 2 mL of normal saline. This design enabled intraindividual comparison between RF-only and RF plus PN-treated sides.

Immediately after completion of the randomized split-face intervention, a regenerative topical Goldstem ampoule (Reteenage Co., Republic of Korea) was applied to the entire face. Patients were instructed to avoid facial cleansing for the first 24 hours. On the following day, only water rinsing was permitted, and the same ampoule was applied without the use of soap or cleansers. For optimal recovery, patients were advised to refrain from applying makeup or sunscreen for as long as possible during the initial healing phase.

Evaluation Tools and Outcome Measures

Pore and Wrinkle Analysis Using 3D Scanner

Three-dimensional facial images were captured using the Quantificare 3D LifeViz (QuantifiCare S.A.S., Sophia Antipolis, France) camera system. Pore size and wrinkle depth in the central face were quantified through automated image analysis, with numerical data extracted from the integrated software.

TEWL, SCH, and Skin Score Measurements

Skin barrier function and hydration were objectively assessed using the GPSkin Barrier Pro (GPOWER, Seoul, Republic of Korea). Measurements were taken from the midface malar area (defined as the vertical line descending from the lateral canthus to the cheek prominence). The device evaluated TEWL via a pseudo-closed chamber sensor, and SCH using bioimpedance spectroscopy. Skin score, a composite index based on TEWL and SCH values. Measurements were recorded at baseline and 6 weeks after the initial treatment.

Dermal Thickness Measurement

Ultrasound imaging was conducted using a 22-MHz linear probe (hockey-stick type) on the Samsung RS85 ultrasound system (Samsung Medison, Seoul, Republic of Korea). Dermal thickness at identical anatomic sites was measured before treatment and at 6 weeks posttreatment to evaluate dermal remodeling.

Skin Elasticity

Cutaneous elasticity was measured using the IMATE skin tester (Guangzhou Zhongke Medical Cosmetic Instrument Co., Ltd., Guangzhou, China), a noninvasive handheld device utilizing dielectric impedance algorithms and AI-based big data analysis. Elasticity scores were acquired bilaterally from the same facial regions.

Patient-reported Outcomes

Subjective recovery experience was assessed using a structured questionnaire that evaluated postprocedure erythema, thermal sensation, and time to recovery for each facial side. Patient satisfaction regarding pore size and wrinkle improvement was rated using the Global Aesthetic Improvement Scale at the final visit.

Duration of posttreatment erythema (24-h redness subsidence): Patients scored the rate at which erythema subsided on each side using the following 5-point Likert scale: 5, erythema subsided much faster on the PN-injected side; 4, faster; 3, slightly faster. 2, no difference; and 1, erythema lasted longer on the PN-injected side.

Perceived heat sensation (burning) over 24 hours post-RF: Patients were asked to rate the degree of perceived burning sensation on both hemifaces over the 24-hour posttreatment period using the following 5-point scale: 5, much less burning on the PN-injected side; 4, less burning; 3, slightly less burning; 2, no difference; and 1, more burning on the PN-injected side.

Perceived clinical improvements at 6 weeks posttreatment: At the 6-week follow-up visit, patients rated perceived improvement in fine wrinkles, skin elasticity, and pore size between the two sides using the following 5-point Likert scale: 5, PN-injected side showed much greater improvement; 4, greater improvement; 3, slightly greater improvement; 2, similar improvement on both sides; and 1, less improvement on the PN-injected side.

Statistical Analysis

All outcome variables were analyzed using paired t tests to compare the PN-injected (right) and control (left) sides within each participant. Continuous variables were expressed as mean ± SD. A P value of less than 0.05 was considered statistically significant. Data analysis was conducted using SPSS version 27.0 (IBM Corp., Armonk, NY).

RESULTS

Patient Characteristics and Overall Clinical Course

Twenty-five female patients were enrolled in this prospective split-face study, and all participants completed the study protocol and the 6-week follow-up. No participants withdrew, and no serious adverse events or treatment-related complications were observed. Clinical photographs demonstrated faster resolution of posttreatment erythema and earlier improvement in skin surface appearance on the PN-treated hemiface compared with the RF-only side (Figs. 1–3). (See figure, Supplemental Digital Content 1, which displays the quantitative skin analysis at 6 weeks demonstrating pore and wrinkle improvement following combined RF and PN treatment for a 42-year-old woman [Fig. 3], https://links.lww.com/PRSGO/F264.) (See figure, Supplemental Digital Content 2, which displays the quantitative skin analysis demonstrating enhanced pore and wrinkle improvement 6 weeks following combined RF and PN treatment for a 55-year-old woman, https://links.lww.com/PRSGO/F265.)

Fig. 1.

Fig. 1.

Immediate and 24 hours posttreatment erythema following needle RF for a 38-year-old woman. A, Right hemiface (PN-treated) and (B) left hemiface (RF-only) immediately after treatment showing diffuse erythema. C, Right and (D) left hemiface at 24 hours, demonstrating faster erythema resolution on the PN-treated side.

Fig. 3.

Fig. 3.

Clinical photographs demonstrating erythema reduction and pore improvement after third session for a 42-year-old woman. A, Immediately after the third session of needle-based fractional RF treatment, erythema is diffuse and prominent bilaterally. B, Right hemiface 12 hours posttreatment, following 3 sessions of RF and 2 prior PN injections. Notable improvements include accelerated erythema resolution and visibly refined pores. C, Left hemiface 12 hours post-third session, showing comparatively slower recovery and more persistent redness. D, At 6 weeks posttreatment, the right hemiface continues to demonstrate superior outcomes in pore size reduction and textural refinement, supporting the cumulative benefit of adjunctive PN administration.

Fig. 2.

Fig. 2.

Accelerated erythema resolution and surface smoothing 12 hours after the third RF+PN session. The right hemiface (A) shows faster resolution of erythema and smoother surface texture compared to the left (B), which demonstrates more persistent redness and coarse texture. These findings suggest accelerated epidermal recovery and improved postprocedural response with adjunctive PN injection.

Clinical Outcomes: Pore and Wrinkle Scores

Quantitative analysis revealed differential improvements in pore size and wrinkle severity between the two hemifacial treatments.

On the left hemiface, which received needle RF treatment only, the pore score showed a modest improvement from 8.13 ± 0.85 to 9.08 ± 1.77. The wrinkle score significantly improved from 8.96 ± 1.57 to 12.63 ± 1.47 (P < 0.001), indicating meaningful rejuvenation effects with RF alone (Fig. 4).

Fig. 4.

Fig. 4.

Comparative quantitative analysis of pore and wrinkle scores before and after treatment. Although both sides showed wrinkle improvement, the PN-treated side demonstrated markedly superior pore reduction, supporting the synergistic effect of PN in enhancing post-RF skin texture.

On the right hemiface, which received needle RF followed by PN injection, the pore score showed a highly significant improvement from 7.96 ± 0.75 to 12.75 ± 1.57 (P < 0.001), suggesting a synergistic enhancement of skin texture with PN application. The wrinkle score also improved from 8.46 ± 1.41 to 13.50 ± 1.44 (P < 0.001), though the increment was not substantially greater than RF-only treatment on the left.

These results suggest that although both RF and RF+PN treatments improve wrinkle severity, the addition of PN significantly enhances pore tightening effects, likely due to its regenerative impact on the dermal matrix and skin texture.

Pore Size Improvement Analysis

On the left hemiface, which received only FN-RF treatment, the mean pore score increased modestly from 8.13 to 9.08. This improvement was statistically significant (paired t test, P = 0.0227), indicating that needle RF alone can enhance pore appearance to some extent.

In contrast, the right hemiface, which received PN injection immediately following needle RF treatment, showed a much more substantial improvement in pore scores, increasing from 7.96 to 12.75. This change was highly statistically significant (paired t test, P = 3.08 × 10−13), demonstrating a pronounced synergistic effect of polynucleotide injection on pore reduction.

These findings suggest that the combination of needle RF followed by PN injection leads to significantly greater pore size improvement compared to RF alone, with strong statistical evidence supporting its clinical efficacy (Table 1). (See Video 1 [online], which displays the 3D topographic analysis of crow’s feet wrinkle improvement in a 55-year-old woman [Supplemental Digital Content 2, https://links.lww.com/PRSGO/F265] 6 weeks after split-face treatment.) (See Video 2 [online], which displays the 3D topographic analysis of pore size improvement following FN-RF with adjunctive PN injection [Supplemental Digital Content 2, https://links.lww.com/PRSGO/F265].)

Table 1.

Clinical Outcomes: Pore and Wrinkle Scores

Pore Score Wrinkle Score
Before After Before After
Left (RF only) 8.13 9.08 8.96 12.63
Right (RF+PN) 7.96 12.75 8.46 13.5

Video 1. This video demonstrates three-dimensional topographic surface analysis of the lateral periorbital region in a 55-year-old female (SDC2) 6 weeks after split-face treatment. The right hemiface received fractional needle radiofrequency followed by polynucleotide injection, whereas the left hemiface received radiofrequency alone. The PN-treated side demonstrates a smoother skin surface and a greater reduction in crow's feet wrinkle depth compared with the control side, illustrating the objective topographic changes observed after combination treatment.

Download video file (4.9MB, mp4)

Video 2. This video demonstrates three-dimensional topographic surface analysis of the lateral cheek in a 55-year-old female (SDC2) 6 weeks after split-face treatment. The patient's right hemiface (left side of the video), treated with fractional needle radiofrequency followed by polynucleotide injection, demonstrates a smoother skin surface with a greater reduction in pore size and depth. The patient's left hemiface (right side of the video), treated with radiofrequency alone, shows comparatively less improvement. The video illustrates the objective topographic differences between combination therapy and radiofrequency monotherapy.

Download video file (3.4MB, mp4)

TEWL, SCH, and Skin Score

Skin Barrier Function and Hydration Outcomes

At baseline, the mean skin scores of the left midface (treated with needle RF alone) and the right midface (treated with needle RF followed by PN injection) were similar, measuring 81.08 and 81.31, respectively. After 6 weeks, the left side exhibited only a minimal improvement to 83.50, whereas the PN-treated side showed a significant enhancement to 93.35, indicating a more pronounced restoration of the skin barrier on the PN-treated side.

TEWL remained relatively stable on the left side, with a slight increase from 8.12 to 8.31. In contrast, the TEWL on the right side significantly decreased from 8.19 ± 3.19 to 3.85 ± 2.41 following PN injection. A paired t test confirmed this change to be statistically significant (t = 9.24, P < 0.001), supporting the hypothesis that PN enhances epidermal barrier integrity and reduces water loss when applied after RF treatment.

SCH showed a modest increase on the left side, from 22.54 to 29.69, which was not statistically significant. However, the right side demonstrated a marked increase in SCH from 23.42 to 48.19 following PN administration. The improvement was highly statistically significant (t = 12.1, P < 0.0001, paired t test), indicating that PN significantly enhances skin hydration. This effect is attributed to the humectant properties and tissue-reparative functions of polynucleotides, which may stimulate extracellular matrix restoration and water retention in the stratum corneum (Fig. 5; Table 2). (See figure, Supplemental Digital Content 3, which displays the comparative facial skin hydration scores before and after 2 treatment sessions in a 40-year-old woman, https://links.lww.com/PRSGO/F266.) (See figure, Supplemental Digital Content 4, which displays the significant increase in skin hydration and barrier function on the PN-treated side compared to control in a 39-year-old woman, https://links.lww.com/PRSGO/F267.) (See figure, Supplemental Digital Content 5, which displays the marked improvement in skin barrier function and hydration following RF with PN on the right hemiface in a 35-year-old woman, https://links.lww.com/PRSGO/F268.) (See figure, Supplemental Digital Content 6, which displays the enhanced SCH on the PN-treated side following 2 sessions of RF-based rejuvenation in a 40-year-old woman [Supplemental Digital Content 3, https://links.lww.com/PRSGO/F266]. https://links.lww.com/PRSGO/F269.) (See figure, Supplemental Digital Content 7, which displays the enhanced skin hydration and barrier function following RF and PN combination treatment in a 42-year-old woman [Fig. 3], https://links.lww.com/PRSGO/F270.)

Fig. 5.

Fig. 5.

Quantitative comparison of skin hydration, TEWL, and overall skin score following RF with or without PN injection. 4 weeks posttreatment, the RF-only side demonstrated modest improvements in skin score (from 81.1 to 83.5) and SCH (22.5 to 29.7), with a minimal change in TEWL (8.1 to 8.3 g/m2/h). In contrast, the RF+PN side showed substantial enhancement in skin score (from 81.3 to 93.3), a marked reduction in TEWL (8.2 to 3.9 g/m2/h), and a notable increase in SCH (23.4 to 48.2 AU).

Table 2.

Comparison of Skin Barrier and Hydration Parameters between Left and Right Hemiface (n = 25).

Parameter Treatment (Left/Right) Baseline (Mean ± SD) Posttreatment P (Paired t test)
Skin Score Left (RF only) 81.08 ± 5.82 83.50 ± 6.13 0.086
Right (RF+PN) 81.31 ± 5.82 93.35 ± 6.20 <0.001
TEWL (g/m2/h) Left (RF only) 8.12 ± 3.19 8.31 ± 2.41 0.487
Right (RF+PN) 8.19 ± 3.19 3.85 ± 2.41 <0.001
SCH Left (RF only) 22.54 ± 4.9 29.69 ± 6.3 0.079
Right (RF+PN) 23.42 ± 5.2 48.19 ± 7.1 <0.0001

Bold values indicate statistically significant differences (P < 0.05).

Taken together, these results indicate that needle RF followed by PN injection results in superior skin barrier restoration, greater moisture retention, and reduced water loss, compared to needle RF treatment alone. The statistically significant improvements in both TEWL and SCH further validate the regenerative and barrier repair capabilities of PN as a post-RF adjunctive therapy.

Dermal Thickness Analysis by 3D Ultrasonography (Malar Region)

Dermal thickness was measured at 5 standardized malar subregions per subject, and the mean values were compared before and after treatment. The left hemiface, treated with needle RF alone, showed no significant change in dermal thickness (mean: 0.9756 mm before versus 0.9774 mm after; SD: 0.2196 versus 0.2229). Similarly, the right hemiface, which received additional PN injection after RF, exhibited a comparable pattern (mean: 0.9773 mm before versus 0.9859 mm after; SD: 0.2188 versus 0.2190). There was no statistically significant difference in dermal thickness change between the two sides, suggesting that although PN enhanced hydration and barrier function, it did not induce additional dermal thickening compared to RF treatment alone within the observed timeframe.

Elasticity Analysis

Skin elasticity was assessed to evaluate dermal firmness changes following treatment. The left hemiface, treated with RF alone, demonstrated a modest increase of approximately 3.12% in elasticity (from 55.56 ± 2.35 to 57.29 ± 2.04). In contrast, the right hemiface, which received additional PN injection after RF, showed a slightly greater increase of approximately 5.45% (from 54.98 ± 3.34 to 57.97 ± 1.98). However, the difference between the two sides was not statistically significant (P = 0.573). These findings suggest that although PN may contribute to a trend toward improved elasticity, a single session may be insufficient to induce significant dermal firmness enhancement. Multiple treatment sessions or extended follow-up may be necessary to achieve meaningful and measurable improvements in skin elasticity. There was no statistically significant difference in elasticity between sides, suggesting that short-term PN injection post-RF may not significantly enhance dermal firmness beyond the effect of RF alone.

Patient-reported Outcomes

Patient-reported assessments further supported the objective findings of the study. Regarding the resolution of posttreatment erythema within 24 hours, patients reported that the PN-injected side demonstrated a faster subsidence of redness compared to the RF-only side, with a mean score of 4.26 ± 0.78 on a 5-point Likert scale (where 5 = much faster resolution) (Fig. 6).

Fig. 6.

Fig. 6.

Patient-reported outcome scores following needle RF alone vs needle RF combined with Rejuran treatment. Patients reported high satisfaction with early resolution of erythema (mean 4.2) and reduction in burning sensation (mean 4.1). Long-term improvements were also noted in fine wrinkles (mean 2.9), skin elasticity (mean 2.2), and pore size (mean 3.6), suggesting perceived clinical benefit from RF ± Rejuran treatment.

Similarly, the perceived burning sensation over the 24-hour period following needle RF treatment was lower on the PN-treated side, with a mean score of 4.13 ± 0.72, indicating reduced subjective discomfort when PN was injected after RF.

At the 6-week follow-up, patients rated the PN-treated hemiface as superior in overall skin quality parameters. The perceived improvement in fine wrinkles was rated at 2.85 ± 0.94, skin elasticity at 2.12 ± 0.88, and pore size at 3.55 ± 0.91. These scores suggest that although subjective improvements in elasticity were moderate, noticeable enhancement in pore refinement and wrinkle reduction were more apparent on the PN-treated side.

These patient-reported outcomes align with the instrumental data, highlighting the enhanced tolerability and perceptible efficacy of PN as a post-RF adjunctive therapy.

DISCUSSION

This split-face, controlled clinical study demonstrates that combining PN with needle RF treatment yields superior outcomes in skin quality restoration compared to RF monotherapy, particularly in parameters such as pore refinement, skin hydration, and barrier function recovery.

Pore and wrinkle scores improved on both sides, but the PN-treated hemiface showed a significantly greater improvement in pore scores (Δ +4.79, P < 0.001), compared to the RF-only side (Δ +0.95, P = 0.0227). This strongly suggests that PN enhances dermal remodeling beyond the thermal coagulation and collagen contraction induced by RF alone. Wrinkle improvement was observed on both sides (Δ +3.67 versus Δ +5.04), and although the RF+PN side showed a numerically higher score, the incremental benefit over RF alone was less pronounced. This may reflect the combined effects of dermal collagen stimulation by RF and the regenerative potential of PN, although wrinkle depth and morphology may require longer observation or volumetric adjuncts to achieve clinically distinguishable superiority. Prior studies have suggested that PN stimulates fibroblast proliferation and collagen synthesis,24 which may result in dermal tightening and pore size reduction. These effects likely synergize with the collagen-denaturing thermal injury induced by RF to yield enhanced aesthetic improvement.24

Although wrinkle scores improved in both groups (RF: Δ +3.67, RF+PN: Δ +5.04), the additional benefit from PN was less striking.25

TEWL and SCH outcomes strongly favor the adjunctive use of PN. This supports the hypothesis that PN injection enhances epidermal barrier repair, potentially through the stimulation of keratinocyte proliferation, lipid synthesis, and extracellular matrix stabilization. The pronounced improvement in hydration observed with PN adjunctive therapy highlights its potential role in accelerating postprocedural skin recovery rather than inducing immediate structural remodeling. These biophysical measurements provide robust objective evidence that PN accelerates post-RF recovery and strengthens epidermal function. PNs have been shown to enhance keratinocyte proliferation, lipid barrier restoration, and stratum corneum function.26 These mechanisms plausibly account for the superior TEWL improvement observed in this study.26

Ultrasonographic dermal thickness measurements in the malar region revealed no significant difference between RF and RF+PN treatments, suggesting that short-term PN effects are more pronounced in hydration and barrier integrity rather than inducing measurable volumetric dermal thickening. Similarly, elasticity analysis revealed modest increases on both sides (3.12% for RF alone versus 5.45% for RF+PN), yet the between-group difference was not statistically significant. This suggests that although a trend toward enhanced firmness was observed, a single session may be insufficient to elicit significant mechanical changes in the dermis. Repeated treatments or longer follow-up may be necessary to capture structural remodeling outcomes. Prior imaging-based trials suggest that meaningful increases in dermal volume from PN require 8–12 weeks or repeated injections.20

Subjective assessments reinforced the instrumental findings. Patients reported faster resolution of posttreatment erythema (mean: 4.26 ± 0.78) and lower burning sensation (mean: 4.13 ± 0.72) on the PN-treated side. At 6 weeks, subjective ratings for fine wrinkle reduction (2.85 ± 0.94), elasticity (2.12 ± 0.88), and pore size (3.55 ± 0.91) favored the PN-treated hemiface, further substantiating patient-perceived efficacy and tolerability. These findings correlate well with previous studies where PN reduced inflammatory cytokines postlaser and RF treatment, accelerating recovery and improving tolerability.27

Several limitations should be acknowledged. First, the relatively short follow-up period (6 wk) may not fully capture the long-term regenerative effects of PN, particularly in parameters such as dermal thickness and elasticity. Second, the sample size, although adequate for exploratory statistical comparison, may be underpowered for detecting subtle differences in some measures. Third, this was a single-session intervention; cumulative or repeated PN injections may yield more robust outcomes. Finally, although the split-face design controls for interindividual variability, localized differences in skin condition and patient behavior (eg, sleep position, skincare routine) may still influence results. This study should be interpreted as an exploratory, hypothesis-generating investigation. A formal a priori sample size calculation and confidence interval estimation were not performed, which limits the ability to generalize the findings or estimate effect sizes with precision.

CONCLUSIONS

This prospective split-face clinical trial demonstrated that adjunctive PN injection following FN-RF treatment significantly enhanced skin barrier recovery, hydration, and pore appearance compared with RF alone. The PN-treated side showed a marked reduction in TEWL and a significant increase in SCH, indicating superior epidermal repair and moisture retention. Clinical pore scores also improved more substantially with PN, suggesting synergistic remodeling effects when combined with energy-based therapy. Although wrinkle scores improved on both sides, the incremental benefit of PN was less pronounced, likely reflecting the limitations of a single-session protocol. Patient-reported outcomes confirmed faster erythema resolution and greater satisfaction with skin texture and hydration on the PN-treated side. Collectively, these findings highlight PN as a valuable adjunct for optimizing post-RF recovery and patient-perceived rejuvenation.

DISCLOSURE

The author has no financial interest to declare in relation to the content of this article.

ACKNOWLEDGMENT

The author expresses sincere gratitude to Dr. Jani van Loghem for his expert insight and support in the development of this study.

Supplementary Material

gox-14-e8109-s003.pdf (3.5MB, pdf)
gox-14-e8109-s004.pdf (3.4MB, pdf)
gox-14-e8109-s005.pdf (3.2MB, pdf)
gox-14-e8109-s006.pdf (2.5MB, pdf)
gox-14-e8109-s007.pdf (2.9MB, pdf)
gox-14-e8109-s008.pdf (2.3MB, pdf)
gox-14-e8109-s009.pdf (2.6MB, pdf)

Footnotes

Published online 28 September 2026.

Disclosure statements are at the end of this article, following the correspondence information.

Related Digital Media are available in the full-text version of the article on www.PRSGlobalOpen.com.

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Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

gox-14-e8109-s003.pdf (3.5MB, pdf)
gox-14-e8109-s004.pdf (3.4MB, pdf)
gox-14-e8109-s005.pdf (3.2MB, pdf)
gox-14-e8109-s006.pdf (2.5MB, pdf)
gox-14-e8109-s007.pdf (2.9MB, pdf)
gox-14-e8109-s008.pdf (2.3MB, pdf)
gox-14-e8109-s009.pdf (2.6MB, pdf)

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