Case Report Case Series: Therapeutic Combination of VoluDerm Radiofrequency Microneedling and Glycolic Acid Peel in Scaled-Up Concentrations
Abstract
Background: Glycolic acid (GA) is an α-hydroxy peeling agent that causes controlled removal of the epidermis, with or without the dermis. Studies have shown the ability of GA to stimulate fibroblast proliferation, induce collagen synthesis, and decrease collagen degradation. The VoluDerm radiofrequency microneedling (RFMN; Pollogen, Tel Aviv, Israel) utilizes an array of microelectrodes to penetrate the epidermis and deliver energy to the skin. The controlled fractional thermal injury promotes neocollagenesis in the correction of skin laxity and wrinkle reduction. It was theorized that GA and VoluDerm could synergistically boost collagen production in combined treatment.
Objectives: Safety and efficacy of the combination treatment were investigated in patients seeking corrections of the age-related skin deteriorations.
Methods: Seven female patients (aged 42-70 years, Fitzpatrick II-IV) with photo- and chrono-damaged skin received 5 treatments of VoluDerm followed by the GA peel at increasing 30% to 70% concentrations.
Results: Clinical photography taken 6 months after the treatment demonstrated improvement in elasticity, wrinkling, roughness, pigmentation, erythema, and pore size across the entire treated group. Efficacy quantified by the physician and patients per 1 to 5 Global Aesthetic Improvement Scale was average 4.3 and 4.5, respectively. The treatments were tolerated well without preprocedural anesthesia. Skin phenom-ena observed after GA application were suggestive of the acid passing to deeper layers.
Conclusions: A novel combination of VoluDerm RFMN and GA at increased concentrations provided safe and effective synergy in the treat-ment of aging facial skin. Visible results demonstrated skin tightening, reduction of rhytidids, and improvement of the skin texture which may be a result of the combination.
Level of Evidence: 4
Glycolic acid (GA) belongs to the group of α-hydroxy acids, the chem-ical peeling agents, which cause controlled removal of the epidermis, with or without the dermis. Studies have shown ability of GA to re-verse the cutaneous aging by stimulating fibroblast proliferation, in-ducing collagen synthesis, and decreasing collagen degradation.1-3 Outcomes of GA peel are determined by the acid pH and the time of exposure to the skin cells. For practical use, pH corresponds to the GA concentration. In concentrations <30%, GA cannot bypass stratum cor-neum (SC) and the peeling effect is associated with the ability to reduce adhesion and cohesiveness of the epidermal corneocytes resulted in desquamation.4 At these low strengths, the peel has been used for tem-porary smoothing the skin and fine wrinkles, reducing solar keratoses, and lightening solar lentigines, but is incapable of affecting deep wrin-kles or deep pigmentations.5 At higher concentrations (50%-70%), GA already demonstrates the ability to penetrate through the epidermal/ dermal junction. In an in vitro study, Jiang and Qureshi1 evidenced the presence of GA in the dermis after applying 40% to 60% GA on fresh human skin samples. The authors concluded that GA at high concentra-tion and low pH “may have disturbed the SC and may result in damage to the skin barrier properties.” Song et al6 demonstrated the reduction Dr Levenberg is a plastic surgeon, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel. Dr Vinshtok is the Clinical Director and Dr Gershonowitz is a Chief Technical Officer, Pollogen Ltd, Tel Aviv, Israel. Corresponding Author:
Dr Yuri Vinshtok, Koifman 6, 61000, Tel Aviv, Israel.
of the skin barrier manifested by increased transepidermal water loss after application of 50% GA to the forearm skin for 3 min. However, the penetration is not uniformed and leads to uneven absorption of the acid in the skin, resulting in focal dermonecrosis and crusting.7-9 Radiofrequency microneedling (RFMN) utilizes an array of micro-needle electrodes to deliver radiofrequency (RF) current to the der-mal layers. The microneedles forcefully penetrate SC and follow with RF emission to create a thermal injury to the dermis. The impact generates fractional zones of thermal ablation and surrounded coag-ulation, which promote neocollagenesis in the correction of skin lax-ity, texture, and wrinkle reduction.10
Contrary to the bleeding and pain associated with mechanical pen-etration in many RFMN devices, VoluDerm RFMN (Divine Pro, Pollogen, Tel Aviv, Israel) uses RF to pass through the epidermis in a miniscule hole and without complications. RF is emitted over the en-tire noninsulated microneedle length and produces a high volume of heat in the dermis. The magnitude of therapeutic impact is deter-mined by the power and duration of the RF pulses. The degree of co-agulation is proportioned to the pulse duration, whereas the depth of the ablation channel is determined by the RF power.11
We theorized that GA and VoluDerm could synergistically boost collagen production if combined in the treatment application. As the initial step, safety and efficacy of the combination were investigat-ed in a small group seeking corrections of the age-related skin deteriorations. METHODS Collection and management of the patient data were conducted in accordance with the ethical guidelines and principles of the 1975 Declaration of Helsinki. A signed informed consent for the treatment procedures and publishing (including images and data) was obtained from all participants in the current investigation prior to the treat-ments. Adult female patients with uneven skin texture, mild-to-deep rhytids, and hyperpigmented spots volunteered for the combination treatments in the outpatient clinic of a certified plastic surgeon (A.L.) between March 2022 and February 2023. Pregnant females and pa-tients with keloidal tendency, active acne, or chronic dermal condi-tions were excluded.
The treatment course included 5 sessions spaced 2 weeks apart. Concentration of GA was progressively increased at each subse-quent session, from the initial 30% to 70%, in increments of 10%. The scale-up was intended to gradually deepen the acid impact.3 Topical GA applied biweekly in scaled-up (35%-70%) concentrations previously demonstrated to be safe and caused only transient ery-thema and burning sensation.12 Treatment Procedures The procedure started with VoluDerm treatment (Video). VoluDerm’s microneedle matrix generates 36 entry points over 1 cm2 skin area at each pass. The entries achieved by the RF-assisted penetration mechanism warranted minimal treatment discomfort. Settings for the pulse power were gradually increased to tolerable maximum to ensure a high ablation depth. The pulse time was set at medium du-ration to avoid overcoagulation. An entire face was treated with a sin-gle pass, while the most problematic areas (deep wrinkles, solar lentils, and prominent skin laxity) received 2 passes. The second
Video. Watch now at https://academic.oup.com/asjopenforum/article-lookup/doi/ 10.1093/asjof/ojae075 stacking pass was applied to the same initial spot with the VoluDerm tip rotated 1-quarter clockwise. The “quarter-turn” maneu-ver increased the density of the stimulation impact without missing the spot.
Immediately after VoluDerm, GA solution was applied over the face in brisk dispersing movements. An instant erythema and patterned micro-edema appeared on the skin and were gradually accompanied by whitish “fog” and the light “frosting.” A flow of cooled air was used to relieve the stinging and burning sensation. After 7 min, GA acidity was neutralized with plenty of cold water. The discomfort was re-lieved, and the frosting and erythema subsided. The treatment proce-dure was completed with topical 0.67% trolamine emollient to hydrate the skin and shorten downtime. Patients were advised to use topical moisturizer and sun protection for 1 week thereafter. Assessment Measures Clinical photographs were taken at baseline and 6 months after the last treatment. Condition of the facial skin was quantified according to the photo-numeric Scientific Assessment Scale of Skin Quality (SASSQ) parameters: elasticity, wrinkles, skin surface roughness, pig-mentation, erythema, and pore size13 (Table 1). Pre- and posttreat-ment measures were compared with the draw conclusion of the changes. Photographic changes were independently graded by the treating physician and patients according to the Global Aesthetic Improvement Scale (GAIS): (5) very much improved, (4) much im-proved, (3) improved, (2) unchanged, and (1) worsened. Procedural discomfort was assessed separately for RFMN and GA, using the 1 to 10 Visual Assessment Scale (VAS).
Participants interviewed 6 months after the original treatment, sub-jectively reported satisfaction with the treatment results as (1) dissat-isfied, (2) undecided, and (3) satisfied. RESULTS Seven patients (age range, 42-70 years, Fitzpatrick range II-IV) with photo- and chrono-damaged skin received the treatment course (Table 2). Six months thereafter, patients reported self-perceived smoothening and tightening of the skin, more defined jawline, and less pigmentation (Figure 1). SASSQ indicated improvement in all cate-gories across the treated group: elasticity decreased by average 40%, wrinkling—by 47%, skin roughness—by 55%, pigmentation—by 38%, erythema—by 33%, and pore size—by 47%. Photo-based changes
a0 = none; 1 = mild; 2 = moderate; 3 = severe; 4 = very severe. were quantified by the physician and the patients at average GAIS of 4.3 and 4.5, respectively. Patients were satisfied with the achieved results at the 6-month follow-up, with a mean satisfaction score of 2.57.
The treatments were tolerated well without preprocedural anes-thesia. The RFMN discomfort was mild, at an average VAS of 4.4. The GA sensation intensified with an increase in the acid concentra-tion and reached an average VAS of 7.6. Cold air was sufficient to re-lieve the skin irritation and patient’s anxiety. DISCUSSION To our knowledge, this is the first trial implementing a novelty combi-nation of RFMN and GA at increased concentrations. Clinical photo-graphs taken 6 months after the treatment course demonstrated not only significant skin resurfacing, but also effective skin tightening and wrinkle smoothing effects. It was assumed that RFMN and GA gener-ated synergistic thermal and chemical impacts that would activate neocollagenesis toward enhanced skin regeneration.
Kim and Won14 showed increased fibroblast proliferation and collagen production in response to GA in a dose dependent manner in vitro. In a histology study, Narda et al15 demonstrated that low-to-medium concentration GA caused desquamation and increased collagen levels by 6% with 8% to 15% GA and by 10.1% with 25% GA.
Accordingly, RFMN thermal impact triggers the wound-healing mechanism to regenerate the degrading extracellular matrix.16 The high temperature generated by RF emission evaporates the tissue along the entire microneedle length and creates a microscopic cone- shaped ablation channel surrounded by the zones of coagulation and volumetric heating, triggering the surrounding viable tissue to induce the biological effect (Figure 2). Gershonowitz and Gat17 reviewed his-tological skin samples taken during the 2-week period after VoluDerm RFMN. An immediate coagulative necrosis in the epider-mis and in the papillary and upper reticular dermis completely re-solved to dermal renewal and epidermal regeneration on Day 14. The healing was accompanied by a significant increase of the epider-mal mitotic index and collagen content, as quantified in an ex vivo hu-man skin model.18 Shapiro19 evaluated VoluDerm for reduction of facial wrinkles in 37 patients. The photographic analysis revealed re-duction in the Fitzpatrick wrinkle score in 97% of cases, along with significant volume enhancement, decrease of nasolabial folds and periorbital lines, and lessening of the skin laxity. The authors related the achieved efficacy to the process of collagen remodeling that con-tinued 3 months after the last treatment. The safety profile of VoluDerm treatments causes low discomfort, does not require anes-thesia, and is associated with less to no downtime.16,19
The impact is structurally similar to the micro-channels created by fractional ablative lasers. The laser photo-thermolysis causes col-umns of the ablation and coagulation zones at the epidermal/dermal
Figure 1. Before and after photographs indicate skin tightening, reduced wrinkles, and improved skin texture 6 months after the treatment: a 62-year-old patient before (A) and after (B), a 72-year-old patient before (C) and after (D), a 42-year-old patient before (E) and after (F). level surrounded by viable tissue.20 The ablation channels were found effective and safe for so-called laser-assisted drug delivery (LADD) in the treatment of melasma, rhytids, and keloids.21 The chan- nels are thought to overcome the epidermal barrier and serve as drug Figure 2. Thermal impacts of noninsulated VoluDerm radiofrequency micronee-dling to the skin: (1) ablation channel, (2) surrounding zone of coagulated tissue, and (3) volumetric area of subnecrotic heating. reservoirs for further diffusion. Hydrophilic liquid materials with low molecular weight were found readily absorbed and diffused through the coagulation zone.22 Rationally, the hydrophilic nature, low molec-ular weight (76.05 g/mol), and high water solubility (0.1 g/mL) provide GA with highly potential for diffusion from the VoluDerm ablation channel.
Artzi et al23 speculated that the micro-wounds created by RFMN could deepen propagation of the peeling agent and thereby lead to better results. In his comparative study, the RFMN combined with immediate 20% trichloroacetic acid (TCA) was shown to improve skin dyschromia, laxity, and wrinkling at higher rate than TCA peeling alone. However, a longer downtime was reported with the combina-tion treatments.
In our investigation, we pretreated the skin with VoluDerm RFMN before applying GA peel at increased concentrations. We assumed that VoluDerm could facilitate transdermal propagation of GA by dis-rupting the SC barrier. Based on the sequential appearance of the skin erythema, edema, fogging, and light frosting, it was concluded that GA could gradually penetrate deeper than it would without RFMN (Figure 3). Generalized erythema was indicative of the acid dif-fused in the epidermis.4 The appearance of micro-edema was due to GA filling the ablation channels and triggering a reactive release of the extracellular fluid. Exposure of the tissue to glycolic acidity led to the peptide denaturation, manifested as whitened haze and light frosting. As an indicator of exfoliation into the dermis, frosting is not achieved with GA at <50% concentration and is usually associat-ed with strong peels like TCA, which has a well-known ability for deep penetration.4 Safety Aspects No serious or systemic events that would require therapy were iden-tified. Procedural bleeding usually expected with RFMN was absent as noninsulated VoluDerm microneedles emitted RF along the entire length and cauterized dermal micro-vessels in the ablated surface. Although intradermal dispersion of glycolic acidity may raise safety concerns, current treatments produce only transient sequalae of er-ythema, edema, fogging, and frosting that subsided after the acid
Figure 3. Skin reaction after combination application of VoluDerm radiofrequency microneedling and glycolic acid in a 42-year-old female patient: (A) immediate micro-edema, erythema, and whitened haze; (B) subsequent skin frosting; and (C) reduced erythema and frosting after the acid neutralization. neutralization. We took into consideration 2 factors determining the degree of the acid impact on the skin—its intensity (directly related to the acid concentration) and duration of the acid exposure to the skin. Accordingly, we optimized the protocol by limiting the highest GA concentration to 70% and by restricting its exposure to 7 min. Due to its hydrophilic nature, GA activity was sufficiently neutralized by washing it off with large amounts of water.24
This is a preliminary report of the novelty treatment approach; therefore, the investigation is limited by the sample size and lack of the control group. Although the safety of the treatments was demon-strated, further investigation is warranted to verify the reproducibility of the effectiveness and clarify the best treatment protocol. Although skin improvement succeeded, further optimization of the VoluDerm parameters would be beneficial. Fine tuning of the pulse duration should provide a degree of coagulation that would not block diffusion of the acid and, at the same time, be sufficient for triggering the wound-healing cascade. CONCLUSIONS A novel combination of RFMN and GA at medium-to-high concentra-tions provides safe synergy in the treatment of aging facial skin. Disclosures Dr Levenberg is the Medical Director of Pollogen Ltd (Tel Aviv, Israel). Dr Levenberg received consulting fees for a period of 36 months prior to the submission of the manuscript for topical activities, but not directly related to the work reported. Dr Levenberg reports no conflicts of interest. Dr Vinshtok is the Clinical Director of Pollogen Ltd and reports no conflicts of inter-est. Dr Gershonowitz is the Chief Technical Officer of Pollogen Ltd and reports no conflict of interest.
Funding The authors received no financial support for the research or authorship of this article. Payment of the article processing char-ge was funded by Pollogen.
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