Open AccessArticle Innovative Facial Contouring Using a Monopolar Radiofrequency Device with Continuous Water Cooling: An Integrated Clinical and Preclinical Study 1 Department of Dermatology & Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul 03722, Republic of Korea 2 Mymirae Dermatologic Clinic, Seoul 07326, Republic of Korea 3 Scar Laser and Plastic Surgery Center, Yonsei Cancer Hospital, Seoul 03722, Republic of Korea 4 Department of Dermatology, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City 70000, Vietnam 5 Mymirae Research Institute for Dermatologic Science, Seoul 07326, Republic of Korea 6 Department of Dermatology, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin-si 16995, Republic of Korea * Author to whom correspondence should be addressed. Int. J. Mol. Sci. 2026, 27(12), 5162; https://doi.org/10.3390/ijms27125162 (registering DOI) Submission received: 15 May 2026 / Revised: 2 June 2026 / Accepted: 4 June 2026 / Published: 6 June 2026 Monopolar radiofrequency (MRF) is a well-established modality for non-invasive facial rejuvenation; however, its clinical utility is frequently constrained by patient discomfort and inconsistent thermal delivery. This study evaluated the efficacy, safety, and mechanistic profile of a novel MRF system incorporating continuous water cooling (RF-CWC) designed to optimize thermal distribution and enhance patient tolerance. In a prospective, single-arm clinical trial involving 22 female participants, a single RF-CWC treatment utilizing region-specific static and sliding delivery modes yielded statistically significant improvements in jawline lifting, alongside a volumetric increase in the midface and a concomitant volumetric reduction in the lower face ( p 0.05). However, the sliding mode showed numerically better results in elastin improvement over 8 weeks ( p > 0.05, Figure 10B). Collagen I expression was significantly elevated at level 4.0 in both modes at week 8 ( p < 0.05, Figure 10C). Collagen III expression was consistently higher in the sliding mode, increasing over time at both energy levels ( p < 0.05, Figure 10D). 2.3.3. Comparison Between Different Numbers of Shots via Static Mode RF-CWC Static mode RF-CWC treatment increased collagen fiber density at all time points, with the 12-shot group showing the greatest and earliest enhancement ( p < 0.05), indicating a dose-dependent and sustained remodeling effect ( Figure 11A). Elastin fiber density followed a similar trend, with the 12-shot group consistently outperforming the 1- and 6-shot groups over 8 weeks ( Figure 11B). 2.3.4. Comparison Between RF-CWC and RF-CSC Both devices significantly increased collagen fiber density compared to the control across all time points and energy levels using 12 shots, with RF-CWC showing consistently higher values than RF-CSC in most conditions ( p < 0.05, Figure 12A). A similar trend was observed for elastin fiber density, especially at level 4.0 ( p < 0.05, Figure 12B). Combined with histological observations ( Figure 5, Figure 6Figure 7), these findings suggest that RF-CWC may deliver better ECM remodelling effects while maintaining a lower degree of treatment-induced inflammation compared to RF-CSC. 2.3.5. Comparison Between Different Energy Levels Across Different Devices, Treatment Modes of RF-CWC, or the Number of Shots of Static Mode RF-CWC 3. Discussion An important contribution of this study is the systematic comparison between shot numbers, devices, and energy levels, which provides practical insight into optimized RF-CWC application. Regarding dose intensity, increasing the number of shots in static mode produced a clear dose-dependent effect, with 12 shots yielding earlier and more sustained ECM remodeling than 1 or 6 shots; thus, higher shot numbers may be preferable for patients with advanced laxity, whereas lower shot numbers may suffice for prejuvenation or maintenance indications. Comparisons between RF-CWC and RF-CSC further demonstrated that RF-CWC achieved better ECM remodeling with reduced inflammatory infiltrates, supporting its use in patients with lower pain tolerance or heightened inflammatory reactivity. Notably, across devices, modes, and shot numbers, energy levels of 2.5 and 4.0 produced largely comparable outcomes, indicating that treatment optimization may rely more on delivery strategy (mode and shot number) than on simply increasing energy. Therefore, individualized treatment protocols tailored to each patient and specific facial region are indispensable. Compared to topical cosmeceuticals, whose efficacy is highly limited by the stratum corneum and carries risks of local irritation [ 41], RF-CWC induces equivalent rejuvenation at a deeper structural level while sparing the epidermis. This clinical advantage is further highlighted when contrasting RF-CWC with other energy-based devices. While bipolar and multipolar RF systems may cause minimal pain and downtime compared to MRF, their effects remain highly localized, with a more restricted penetration [ 42, 43]. Resurfacing lasers, while able to induce evident skin renewal, incur more complications at greater treatment depths [ 44]. Similarly, high-intensity focused ultrasound (HIFU) delivers focused acoustic energy that generates precise thermal coagulation zones in deep tissue. By targeting the deep reticular dermis, superficial musculoaponeurotic system, and platysma while sparing the epidermis, HIFU effectively improves skin laxity through controlled tissue contraction and neocollagenesis. Nevertheless, while HIFU provides a powerful non-invasive lifting alternative, further clinical research and protocol standardization are still required to fully establish its long-term efficacy [ 45]. Consequently, head-to-head comparative clinical trials are warranted to systematically evaluate the long-term efficacy, safety profiles, and patient tolerance across these distinct energy-based modalities. A key strength of this study lies in its integrative use of clinical, ex vivo, and in vivo models, enabling a comprehensive, translational evaluation supported by molecular evidence that aligns with histological findings. However, several limitations must be acknowledged. The clinical cohort was characterized by a small sample size, a lack of a treated control group, a relatively short follow-up period, and a homogeneous demographic consisting predominantly of females aged 40 and older, all of which may constrain the generalizability of the findings. Regarding the preclinical models, differences between porcine and human dermal physiology warrant caution when extrapolating results. Furthermore, our laboratory analysis lacks pathway-level investigations and mechanistic validation to fully elucidate the molecular cascades underlying RF-CWC-induced rejuvenation. Additionally, although no visible epidermal thermal injury or adverse skin reactions were observed, skin surface temperature was not objectively monitored during treatment—a parameter that would provide deeper insights into the thermal penetration profile of the device. Consequently, future randomized, double-blind, controlled studies incorporating larger, more diverse patient populations, extended follow-up periods, and pathway-specific mechanistic analyses are warranted. Exploring combination approaches with other modalities may also further optimize therapeutic outcomes. 4. Materials and Methods 4.1. Clinical Trial 4.1.1. Clinical Study Design and Patient Selection This prospective single-arm clinical study evaluated the volumizing and contouring effects of RF-CWC (Volnewmer, CLASSYS, Seoul, Republic of Korea) in 22 eligible females who completed the study without dropping out. The protocol was approved by the Clinical Trial Review Board of the Global Medical Research Center (Approval No. GIRB-23614-PM, approval date: 26 June 2023) and registered on clinicaltrials.gov (Identifier: NCT07317089, approval date: 5 January 2026). The study was conducted at the Global Medical Evaluation Academy from July to 13 September 2023, in accordance with the Declaration of Helsinki, and written informed consent was obtained from all participants prior to enrollment. In compliance with Korea’s Ministry of Food and Drug Safety (MFDS) guidelines (Notification No. 2021-55; 2018 Guideline), at least 20 participants were enrolled to ensure statistical validity for comparative analyses. Eligible participants aged 38–50 years agreed to abstain from any dermatological procedures, including facial lifting, during the study and were able to adhere to the study protocol. Exclusion criteria included pregnancy or breastfeeding, failure to comply with contraception, facial lesions, hypersensitivity, inflammatory or infectious facial conditions, recent use of systemic steroids or phototherapy (within 1 month), recent cosmetic procedures (within 3 months), or any condition deemed unsuitable by the investigator. 4.1.2. Treatment Protocol Radiofrequency treatment was performed using the RF-CWC device operating at 6.78 MHz with a maximum power output of 115 W. All treatments were performed using a 4 cm 2 treatment tip (V tip). The system features real-time impedance matching within a range of 75–400 Ω, allowing automatic adjustment of energy output according to tissue resistance, along with additional modulation based on tip contact quality and skin hydration. A continuous water-based contact cooling system is integrated into the handpiece to protect the epidermis while enabling effective dermal heating. The selected energy levels (2.5 and 4.0) were based on the settings most commonly used in actual clinical practice. In addition, the shot numbers were determined to simulate real clinical treatment conditions by calculating the relative exposure area of the experimental tissue compared with the total facial surface area typically treated in humans. Furthermore, different shot conditions were included to evaluate the gradual tissue response and dose-dependent effects according to shot number. Before treatment, a topical anesthetic cream containing 2.5% lidocaine and 2.5% prilocaine (TaiGuk Pharm Co., Ltd., Hwaseong-si, Republic of Korea) was applied evenly for 40 min. Participants then underwent a single RF-CWC treatment on Day 0 (V0) after eligibility screening and baseline assessments. A region-specific dual-mode approach was employed, with static mode targeting the outer facial regions, including the mandibular and jawline areas. In contrast, sliding mode was applied to the central facial regions. Treatment was delivered at a constant power of 65 W (approximately 65 J per shot, equivalent to power level 2.5). Approximately 300 shots were applied in static mode, while another 300 shots were applied in sliding mode using continuous motion, with around 1000 ms per shot. No additional post-procedure care was required. Follow-up visits were conducted at weeks 2 (V1), 4 (V2), and 8 (V3). At each visit, participants received facial cleansing followed by a 30 min acclimatization period under controlled conditions (20–24 °C, 45–55% relative humidity). Skin assessments and safety were assessed by recording and analyzing the incidence of adverse events reported across all participants at each follow-up. 4.1.3. Efficacy Evaluations To objectively quantify topographic changes in facial contours and regional tissue volumes, three-dimensional (3D) facial surface imaging was performed using the Morpheus3D ପ୍ପ system (Morpheus Co., Ltd., Yongin-si, Republic of Korea). This system utilizes a high-resolution, light-emitting diode structured-light scanner to capture dense surface topology and reconstruct an accurate computerized polygon mesh model of the patient’s face under standardized lighting and positioning conditions. Anatomical linear distances and volumetric metrics were computed algorithmically via the system’s dedicated clinical simulation software using the following parameters: Jawline Lifting Analysis: To evaluate lower face lifting effects, specific anatomical landmarks were plotted on the digital 3D mesh. The software calculated the precise Euclidean curved surface distance (mm) along the mandibular border from the chin to the earlobe. A post-treatment decrease in this linear metric indicated a jawline-lifting effect. Regional Volumetric Analysis: Volumetric changes (mL) were determined by digitally aligning and superimposing pre-treatment and post-treatment 3D facial scans via a rigid surface-matching registration algorithm. The software computed the exact spatial volume bounded between the two superimposed surface shells within the midface region (between the eyes and from the philtrum to the nose), where an increase indicated volumization, and within the lower face region (from the philtrum to the chin), where a decrease indicated contouring. 4.2. Ex Vivo Study 4.2.1. Ex Vivo Skin Model Preparation and RF-CWC Treatment Residual human skin samples were collected from a healthy Korean donor who was undergoing breast reconstruction under ethical approval from the Institutional Review Board of Yonsei University College of Medicine, Severance Hospital (IRB No. 4-2023-0635, approval date: 19 August 2023). All experimental procedures were conducted in accordance with the Declaration of Helsinki. Subcutaneous fat was carefully removed, and the tissues were thoroughly washed multiple times with phosphate-buffered saline (PBS) to eliminate residual impurities. The cleaned tissues were then sectioned into 5 cm × 5 cm (width × length) specimens and randomly assigned to one of three experimental groups: (1) untreated control, (2) UVB exposure only, and (3) RF-CWC treatment followed by UVB exposure. RF-CWC treatment was administered using the V tip (4 cm 2), delivering 12 shots per sample at an energy level of 2.5 (16.25 J/cm 2), with inter-shot intervals of 12 s. Following treatment, the tissues were further sectioned into 1 cm × 1 cm specimens and subjected to UVB irradiation. 4.2.2. Enzyme-Linked Immunosorbent Assay (ELISA) To evaluate dermal matrix remodeling, the ex vivo skin tissues collected 72 h post-treatment were homogenized using a TissueLyser II (Qiagen, Hilden, Germany), centrifuged at 2000× g for 10 min, and the supernatant was used for protein analysis. Total protein was quantified using the BCA assay (Sigma-Aldrich, St. Louis, MO, USA) and specific proteins were measured with ELISA kits following manufacturers’ protocols: elastin (Cusabio, Houston, TX, USA), MMP-1 (Abcam, Cambridge, MA, USA), IGF (Abcam), IL-1α (R&D Systems), HA (R&D Systems, Minneapolis, MN, USA), HSP 72 (Biorbyt, Cambridge, UK). Optical density (OD) was measured using a VARIOSKAN LUX microplate reader (Thermo Fisher Scientific, Waltham, MA, USA), and concentrations were calculated from standard curves. All the experiments were repeated at least 3 times. 4.3. In Vivo Study 4.3.1. Animal Breeding Male pigs (XP Bio, Anseong, Republic of Korea) were selected due to their anatomical and physiological similarities to humans, including comparable metabolism and organ structure, making them a suitable model for evaluating medical devices. A total of 9 pigs were included in the experiment to balance statistical validity and ethical use of animals, as using too few animals may miss significant effects, whereas excessive numbers raise ethical and resource concerns [ 49, 50]. The protocol received approval from the Institutional Animal Care and Use Committee (IACUC no. BIOSTEP IACUC 23-KE-0274, approval date: 4 September 2023). This study was conducted in Animal Housing Room No. 1 of HLBIOSTEP Co., Ltd. The animals were housed in a controlled breeding area maintained at 23 ± 3 °C, 55 ± 15% relative humidity, a ventilation rate of 10–20 air changes per hour, a 12 h light–dark cycle, and an illuminance level of 150–300 lux. Environmental parameters—including temperature, humidity, ventilation, and lighting conditions—were regularly monitored throughout the housing period, and no deviations were observed that could have influenced the study outcomes. Feed for growing pigs (Bodybuilder diet, Daehan Feed Co., Ltd., Incheon, Republic of Korea) was supplied by Dream Bio (Gwangjin-gu, Seoul, Republic of Korea), with approximately 600 g provided in a feeder and made available ad libitum. Drinking water was supplied ad libitum and sterilized using ultraviolet irradiation and microfiltration. 4.3.2. Device Application The application conditions for the test device RF-CWC and control device RF-CSC (Thermage FLX, Hayward, CA, USA), including a negative control group, were categorized into 11 treatment conditions based on their mode, energy level, number of shots, and size ( Table 1). Pigs were anesthetized and positioned in a ventral recumbent posture. The dorsal region was shaved, disinfected, and treatment sites were marked using a Surgi-pen. To minimize site-specific bias, treatment locations within each group were randomized on the dorsal region of the pigs to prevent the same condition from being applied to the same anatomical area ( Figure 13). Clinical signs, including mortality, were monitored at 1 h intervals for the first 4 h post-treatment and subsequently once daily. At 2, 4, and 8 weeks post-treatment, animals were euthanized under anesthesia via exsanguination through the external jugular vein, and skin tissue samples were collected for analysis. 4.3.3. Histological Analysis Tissue samples were fixed in 10% neutral-buffered formalin and subsequently embedded in paraffin. Serial sections with a thickness of 5 µm were obtained, mounted onto glass slides, deparaffinized, rehydrated and stained using standard histological techniques: H&E for assessing overall tissue architecture and cell integrity; MT for detecting collagen fibers; and VVG for evaluating elastic fiber remodeling. H&E staining: The sections were stained with hematoxylin solution (S3309; Dako, Glostrup, Denmark). After rinsing under running tap water, cytoplasmic staining was performed using eosin solution (318906; Sigma-Aldrich). The stained sections were subsequently dehydrated, cleared, and mounted using a mounting medium. Images were acquired using a digital slide scanner (Aperio A2, Leica Biosystems, Nussloch, Germany), and representative images were captured at 200× magnification using an eSlide viewing software (Aperio ImageScope version 12.4.6; Leica Biosystems). MT staining: The sections were mordanted in Bouin’s solution (2010; BBC Biochemical, Mount Vernon, WA, USA) and rinsed under running tap water, followed by nuclear staining with Weigert’s iron hematoxylin (hematoxylin: 4077-4425, Daejung, Siheung, Republic of Korea; ferric chloride: 660, Duksan). Cytoplasm and muscle fibers were subsequently stained with Biebrich scarlet–acid fuchsin solution (Biebrich scarlet: B6008; Sigma-Aldrich; acid fuchsin: 4048-4125; Daejung). The sections were then differentiated and mordanted using a phosphomolybdic–phosphotungstic acid solution (phosphomolybdic acid hydrate: 84235S0410; phosphotungstic acid hydrate: 84220S0410, Junsei, Chuo-ku, Tokyo, Japan). Without intermediate rinsing, collagen fibers were stained with aniline blue (1087-4125, Daejung), and excess dye was removed by treatment with acetic acid. The stained sections were rinsed, dehydrated, cleared, and mounted. Images were acquired using an Aperio A2 slide scanner, and representative images were analyzed at 200× magnification using ImageScope software. Quantitative image analysis was performed using ImageJ software (version 1.54g, NIH, Bethesda, MD, USA) to measure the total area of the papillary dermis and the area occupied by collagen fibers (blue). Collagen fiber density was calculated as the percentage of collagen fiber area relative to the total papillary dermis area. VVG staining: The sections were stained with Verhoeff’s solution and differentiated with freshly prepared 2% ferric chloride solution (451649, Sigma-Aldrich), followed by treatment with 5% sodium thiosulfate to remove residual iodine. Counterstaining was performed using Van Gieson solution. The stained sections were dehydrated, cleared, and mounted. Whole-slide images were acquired using the Aperio A2 slide scanner and analyzed at 200× magnification using ImageScope software. Quantitative analysis was performed using Zen Image Analysis software (ZEN 3.4, Carl Zeiss Microscopy GmbH, Jena, Germany) to measure the total papillary dermis area and the area occupied by elastic fibers (black). Elastic fiber density was calculated as the percentage of elastic fiber area relative to the total papillary dermis area. 4.3.4. IHC Staining Tissue samples collected at 2, 4, and 8 weeks post-treatment were fixed in 10% formalin, embedded in paraffin, and sectioned. After deparaffinization and antigen retrieval, primary antibodies specific to collagen I (MA1-26771, Invitrogen, CA, USA) and collagen III (ab7778, Abcam) were applied, followed by secondary antibodies (anti-mouse: K4001 for collagen I; anti-rabbit: K4003 for collagen III, Dako). Slides were counterstained with hematoxylin (SM806, Dako), mounted, and imaged at 200× magnification using a light microscope (BX43F, Olympus, Tokyo, Japan). Positive staining areas in the dermis were quantified using ImageJ, with greater positive areas indicating higher protein expression. The expression of collagen I and III was evaluated specifically within the dermal region, where collagen fibers are primarily distributed, and quantitative analysis was performed by defining the dermal area as the region of interest. The epidermal region and nuclear staining patterns were not included in the quantitative assessment. All the experiments were repeated at least 3 times. 4.4. Statistical Analysis Statistical analyses were performed using IBM SPSS Statistics (version 27.0, IBM Corp., Armonk, NY, USA), with significance set at p < 0.05. Graphs were created using GraphPad Prism (version 10.2.2; GraphPad Software, Boston, MA 02110, USA). In the in vivo and ex vivo studies, normality was assessed prior to between-group comparisons, followed by either an independent t-test for parametric values or a Mann–Whitney test for non-parametric values. For within-group comparisons over time in the clinical study, a repeated-measures ANOVA or the Friedman test was used based on normality, followed by a post hoc analysis using the Wilcoxon signed-rank test with Bonferroni correction. 5. Conclusions RF-CWC, a novel MRF device with a CWC system, demonstrated safe and effective facial rejuvenation through zone-specific application of static and sliding modes. Preclinical data confirmed its ability to remodel the ECM, reduce inflammation, and enhance dermal stability. Compared to conventional systems, RF-CWC might offer better clinical flexibility and safety. Future randomized, double-blind, controlled trials incorporating diverse populations and longer follow-up are needed to confirm its therapeutic potential. Supplementary Materials The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/ijms27125162/s1. Author Contributions Conceptualization, H.R. and J.K.; methodology, H.R., Y.I.L. and J.J.; software, N.H.N. and J.K.H.; validation, H.R. and Y.I.L.; formal analysis, H.R., J.J., N.H.N. and J.K.H.; data curation, H.R., Y.I.L. and J.J.; investigation, H.R. and J.K.H.; visualization, H.R. and N.H.N.; writing—original draft, H.R., Y.I.L. and N.H.N.; writing—review and editing, H.R., J.J., N.H.N., J.K.H. and J.K.; supervision, J.K.; project administration, J.K. All authors have read and agreed to the published version of the manuscript. Funding This study was supported by an MEF Fellowship conducted as part of the ‘Education and Research Capacity Building Project at the University of Medicine and Pharmacy at Ho Chi Minh City,’ implemented by the Korea International Cooperation Agency (KOICA) during 2021–2026. (No. 2021-00020-5). Institutional Review Board Statement The clinical trial protocol was approved by the Clinical Trial Review Board of the Global Medical Research Center (Approval No. GIRB-23614-PM, 26 June 2023). Human skin tissues in the ex vivo studies were obtained under ethical approval (IRB No. 4-2023-0635, approval date: 19 August 2023) from the Institutional Review Board of Yonsei University College of Medicine, Severance Hospital, and all experiments were conducted in accordance with the Declaration of Helsinki. The in vivo study protocol received approval from the Institutional Animal Care and Use Committee (IACUC no. BIOSTEP IACUC 23-KE-0274, approval date: 4 September 2023). Trial registration: clinicaltrials.gov, identifier: NCT07317089 (approval date: 5 January 2026). Informed Consent Statement Informed consent was obtained from all subjects involved in the study. Data Availability Statement The original contributions presented in this study are included in the article/ Supplementary Material. Further inquiries can be directed to the corresponding author. Conflicts of Interest The authors declare no conflicts of interest. Abbreviations The following abbreviations are used in this manuscript: ECM Extracellular matrix ELISA Enzyme-linked immunosorbent assay HA Hyaluronic acid H&E Hematoxylin and eosin HSP 72 Heat shock protein 72 IGF Insulin-like growth factor IHC Immunohistochemistry IL Interleukin IL-1α Interleukin-1 alpha MMP-1 Matrix metalloproteinase-1 MRF Monopolar radiofrequency MT Masson’s trichrome PBS Phosphate-buffered saline RF Radiofrequency RF-CSC Radiofrequency with cryogen spray cooling RF-CWC Radiofrequency with continuous water cooling UV Ultraviolet UVB Ultraviolet B VVG Verhoeff–Van Gieson References Farkas, J.P.; Pessa, J.E.; Hubbard, B.; Rohrich, R.J. The Science and Theory behind Facial Aging. Plast. Reconstr. Surg. Glob. Open 2013, 1, e8–e15. [] [ CrossRef] [ PubMed] Kang, H.Y.; Lee, J.W.; Papaccio, F.; Bellei, B.; Picardo, M. Alterations of the pigmentation system in the aging process. Pigment. Cell Melanoma Res. 2021, 34, 800–813. [] [ CrossRef] [ PubMed] Zhang, S.; Duan, E. Fighting against Skin Aging: The Way from Bench to Bedside. Cell Transplant. 2018, 27, 729–738. [] [ CrossRef] Gomez, C.R. Role of heat shock proteins in aging and chronic inflammatory diseases. Geroscience 2021, 43, 2515–2532. [] [ CrossRef] Dugan, B.; Conway, J.; Duggal, N.A. Inflammaging as a target for healthy ageing. Age Ageing 2023, 52, afac328. [] [ CrossRef] Haykal, D.; Nahai, F.; Cartier, H. Prejuvenation: The Global New Anti-Aging Trend. Aesthetic Surg. J. Open Forum 2023, 5, ojad061. [] [ CrossRef] Goldman, M.P.; Kilmer, S.L.; Biesman, B.; McPherson, K.; Jacobson, A. Monopolar Radiofrequency-Induced Fibroblast Stimulation for the Prevention and Improvement of Skin Laxity. Dermatol. Surg. 2025, 51, S38–S43. [] [ CrossRef] Vale, A.L.; Pereira, A.S.; Morais, A.; Noites, A.; Mendonca, A.C.; Martins Pinto, J.; Vilarinho, R.; Carvalho, P. Effects of radiofrequency on adipose tissue: A systematic review with meta-analysis. J. Cosmet. Dermatol. 2018, 17, 703–711. [] [ CrossRef] [ PubMed] Bonjorno, A.R.; Gomes, T.B.; Pereira, M.C.; de Carvalho, C.M.; Gabardo, M.C.L.; Kaizer, M.R.; Zielak, J.C. Radiofrequency therapy in esthetic dermatology: A review of clinical evidences. J. Cosmet. Dermatol. 2020, 19, 278–281. [] [ CrossRef] Fitzpatrick, R.; Geronemus, R.; Goldberg, D.; Kaminer, M.; Kilmer, S.; Ruiz-Esparza, J. Multicenter study of noninvasive radiofrequency for periorbital tissue tightening. Lasers Surg. Med. 2003, 33, 232–242. [] [ CrossRef] Angra, K.; Alhaddad, M.; Boen, M.; Lipp, M.B.; Kollipara, R.; Hoss, E.; Goldman, M.P. Prospective Clinical Trial of the Latest Generation of Noninvasive Monopolar Radiofrequency for the Treatment of Facial and Upper Neck Skin Laxity. Dermatol. Surg. 2021, 47, 762–766. [] [ CrossRef] Abraham, M.T.; Chiang, S.K.; Keller, G.S.; Rawnsley, J.D.; Blackwell, K.E.; Elashoff, D.A. Clinical evaluation of non-ablative radiofrequency facial rejuvenation. J. Cosmet. Laser Ther. 2004, 6, 136–144. [] [ CrossRef] [ PubMed] Zelickson, B.D.; Kist, D.; Bernstein, E.; Brown, D.B.; Ksenzenko, S.; Burns, J.; Kilmer, S.; Mehregan, D.; Pope, K. Histological and ultrastructural evaluation of the effects of a radiofrequency-based nonablative dermal remodeling device: A pilot study. Arch. Dermatol. 2004, 140, 204–209. [] [ CrossRef] [ PubMed] Abraham, M.T.; Mashkevich, G. Monopolar radiofrequency skin tightening. Facial Plast. Surg. Clin. N. Am. 2007, 15, 169–177. [] [ CrossRef] Jaffary, F.; Nilforoushzadeh, M.A.; Zarkoob, H. Patient satisfaction and efficacy of accent radiofrequency for facial skin wrinkle reduction. J. Res. Med. Sci. 2013, 18, 970–975. [] Roh, H.; Lee, Y.I.; Lee, S.G.; Hwang, J.K.; Jung, J.; Lee, J.H. Comparative Analysis on the Efficacy of Monopolar Radiofrequency With Continuous Water Cooling and Conventional Cryogen Spray Cooling in Facial Rejuvenation. Ann. Dermatol. 2025, 37, 397–407. [] [ CrossRef] [ PubMed] Kim, J. Evaluating the Efficacy of Continuous Water-Cooling 115-Watt 6.78-MHz Monopolar RF Therapy for Fine Wrinkle Reduction. Plast. Reconstr. Surg. Glob. Open 2024, 12, e5623. [] [ CrossRef] Yang, Y.S.; Kim, D.H.; Ha, J.H.; Ko, N.Y.; Kim, J.K.; Choi, W.J.; Song, B.H.; Hwang, S.H.; Sohn, K.M.; Ahn, H.J. A Split-face Study on Rejuvenation Efficacy According to Monopolar Radiofrequency Tip Size. J. Clin. Aesthet. Dermatol. 2024, 17, 20–22. [] Kim, J. Comparative Three-dimensional Analysis of Facial Lifting Effects across Five Aesthetic Units following Continuous Radiation 115-Watt 6.78-MHz Monopolar Radiofrequency Therapy. Plast. Reconstr. Surg. Glob. Open 2024, 12, e6137. [] [ CrossRef] Chaffoo, R.A. Complications in facelift surgery: Avoidance and management. Facial Plast. Surg. Clin. N. Am. 2013, 21, 551–558. [] [ CrossRef] Galadari, H.; Krompouzos, G.; Kassir, M.; Gupta, M.; Wollina, U.; Katsambas, A.; Lotti, T.; Jafferany, M.; Navarini, A.A.; Vasconcelos Berg, R.; et al. Complication of Soft Tissue Fillers: Prevention and Management Review. J. Drugs Dermatol. 2020, 19, 829–832. [] [ CrossRef] Niu, Z.; Zhang, K.; Yao, W.; Li, Y.; Jiang, W.; Zhang, Q.; Troulis, M.J.; August, M.; Chen, Y.; Han, Y. A Meta-Analysis and Systematic Review of the Incidences of Complications Following Facial Thread-Lifting. Aesthetic Plast. Surg. 2021, 45, 2148–2158. [] [ CrossRef] Hamilton, M.M.; Kao, R. Recognizing and Managing Complications in Laser Resurfacing, Chemical Peels, and Dermabrasion. Facial Plast. Surg. Clin. North. Am. 2020, 28, 493–501. [] [ CrossRef] Heidari Beigvand, H.; Razzaghi, M.; Rostami-Nejad, M.; Rezaei-Tavirani, M.; Safari, S.; Rezaei-Tavirani, M.; Mansouri, V.; Heidari, M.H. Assessment of Laser Effects on Skin Rejuvenation. J. Lasers Med. Sci. 2020, 11, 212–219. [] [ CrossRef] Vassao, P.G.; Balao, A.B.; Credidio, B.M.; Do Vale, G.C.A.; Assis Garcia, L.; Martignago, C.C.S.; Parisi, J.R.; Laakso, E.L.; Renno, A.C.M. Radiofrequency and skin rejuvenation: A systematic review. J. Cosmet. Laser Ther. 2022, 24, 9–21. [] [ CrossRef] [ PubMed] Swift, A.; Liew, S.; Weinkle, S.; Garcia, J.K.; Silberberg, M.B. The Facial Aging Process From the “Inside Out”. Aesthetic Surg. J. 2021, 41, 1107–1119. [] [ CrossRef] [ PubMed] Wan, D.; Amirlak, B.; Rohrich, R.; Davis, K. The clinical importance of the fat compartments in midfacial aging. Plast. Reconstr. Surg. Glob. Open 2013, 1, e92. [] [ CrossRef] Cohen, S.; Artzi, O.; Mehrabi, J.N.; Heller, L. Vectorial facial sculpting: A novel sub-SMAS filler injection technique to reverse the impact of the attenuated retaining ligaments. J. Cosmet. Dermatol. 2020, 19, 1948–1954. [] [ CrossRef] [ PubMed] Kapoor, K.M.; Saputra, D.I.; Porter, C.E.; Colucci, L.; Stone, C.; Brenninkmeijer, E.E.A.; Sloane, J.; Sayed, K.; Winaya, K.K.; Bertossi, D. Treating Aging Changes of Facial Anatomical Layers with Hyaluronic Acid Fillers. Clin. Cosmet. Investig. Dermatol. 2021, 14, 1105–1118. [] [ CrossRef] Lee, S.; Hyun, J.; Shin, Y.; Leo Goo, B. Efficacy and safety of a novel monopolar radiofrequency device with a continuous water-cooling system in patients with age-related facial volume loss. J. Dermatol. Treat. 2024, 35, 2333028. [] [ CrossRef] Shin, J.; Sung, Y.; Jin, S.; Hwang, C.-L.; Kim, H.; Hong, D.; Jung, K.E.; Seo, Y.-J.; Lee, Y. Efficacy and Safety of Monopolar Radiofrequency for Tightening the Skin of Aged Faces. Cosmetics 2024, 11, 71. [] [ CrossRef] Shin, S.H.; Lee, Y.H.; Rho, N.K.; Park, K.Y. Skin aging from mechanisms to interventions: Focusing on dermal aging. Front. Physiol. 2023, 14, 1195272. [] [ CrossRef] Meyer, P.F.; de Oliveira, P.; Silva, F.; da Costa, A.C.S.; Pereira, C.R.A.; Casenave, S.; Valentim Silva, R.M.; Araujo-Neto, L.G.; Santos-Filho, S.D.; Aizamaque, E.; et al. Radiofrequency treatment induces fibroblast growth factor 2 expression and subsequently promotes neocollagenesis and neoangiogenesis in the skin tissue. Lasers Med. Sci. 2017, 32, 1727–1736. [] [ CrossRef] Yoon, J.E.; Kim, Y.; Kwon, S.; Kim, M.; Kim, Y.H.; Kim, J.H.; Park, T.J.; Kang, H.Y. Senescent fibroblasts drive ageing pigmentation: A potential therapeutic target for senile lentigo. Theranostics 2018, 8, 4620–4632. [] [ CrossRef] Oh, S.; Rho, N.K.; Byun, K.A.; Yang, J.Y.; Sun, H.J.; Jang, M.; Kang, D.; Son, K.H.; Byun, K. Combined Treatment of Monopolar and Bipolar Radiofrequency Increases Skin Elasticity by Decreasing the Accumulation of Advanced Glycated End Products in Aged Animal Skin. Int. J. Mol. Sci. 2022, 23, 2993. [] [ CrossRef] [ PubMed] Kogan, G.; Šoltés, L.; Stern, R.; Gemeiner, P. Hyaluronic acid: A natural biopolymer with a broad range of biomedical and industrial applications. Biotechnol. Lett. 2007, 29, 17–25. [] [ CrossRef] Zhang, X.; Hu, F.; Li, J.; Chen, L.; Mao, Y.F.; Li, Q.B.; Nie, C.Y.; Lin, C.; Xiao, J. IGF-1 inhibits inflammation and accelerates angiogenesis via Ras/PI3K/IKK/NF-kappaB signaling pathways to promote wound healing. Eur. J. Pharm. Sci. 2024, 200, 106847. [] [ CrossRef] [ PubMed] Yoon, S.Y.; Kim, K.T.; Jo, S.J.; Cho, A.R.; Jeon, S.I.; Choi, H.D.; Kim, K.H.; Park, G.S.; Pack, J.K.; Kwon, O.S.; et al. Induction of hair growth by insulin-like growth factor-1 in 1,763 MHz radiofrequency-irradiated hair follicle cells. PLoS ONE 2011, 6, e28474. [] [ CrossRef] [ PubMed] Cohen, I.; Rider, P.; Vornov, E.; Tomas, M.; Tudor, C.; Wegner, M.; Brondani, L.; Freudenberg, M.; Mittler, G.; Ferrando-May, E.; et al. IL-1α is a DNA damage sensor linking genotoxic stress signaling to sterile inflammation and innate immunity. Sci. Rep. 2015, 5, 14756. [] [ CrossRef] Kregel, K.C. Heat shock proteins: Modifying factors in physiological stress responses and acquired thermotolerance. J. Appl. Physiol. (1985) 2002, 92, 2177–2186. [] [ CrossRef] Milosheska, D.; Roskar, R. Use of Retinoids in Topical Antiaging Treatments: A Focused Review of Clinical Evidence for Conventional and Nanoformulations. Adv. Ther. 2022, 39, 5351–5375. [] [ CrossRef] Sadick, N.S.; Nassar, A.H.; Dorizas, A.S.; Alexiades-Armenakas, M. Bipolar and multipolar radiofrequency. Dermatol. Surg. 2014, 40, S174–S179. [] [ CrossRef] Zhang, B.; Tan, X.; Zhang, Q.; Wu, M. The Landscape of Radiofrequency Technology for Skin Rejuvenation. Health Sci. Rep. 2026, 9, e71575. [] [ CrossRef] Meghe, S.R.; Khan, A.; Jangid, S.D.; Sarda, B.; Vangala, N.; Saoji, V. Shedding Light on Acne Scars: A Comprehensive Review of CO2 vs. Erbium-Doped Yttrium Aluminium Garnet (Er:YAG) Laser Therapy. Cureus 2024, 16, e57572. [] [ CrossRef] Haykal, D.; Sattler, S.; Verner, I.; Madhumita, M.; Cartier, H. A Systematic Review of High-Intensity Focused Ultrasound in Skin Tightening and Body Contouring. Aesthetic Surg. J. 2025, 45, 690–698. [] [ CrossRef] Roh, H.; Nguyen, N.H.; Jung, J.; Hwang, J.K.; Lee, Y.I.; Baek, Y.; Jung, I.; Kim, J.; Lee, J.H. Therapeutic Anti-Fibrotic Effects of a Dual Hyaluronic Acid Hybrid Complex in Bleomycin-Induced Dermal Fibrosis and UVB-Irradiated Human Skin. Int. J. Mol. Sci. 2026, 27, 3038. [] [ CrossRef] [ PubMed] Baek, Y.; Nguyen, N.H.; Ham, S.; Kim, W.; Lee, J.H.; Lee, Y.I. Monopolar Radiofrequency for Facial Hyperpigmentation Treatment: An Integrated Retrospective Clinical Trial and Ex Vivo Study. Int. J. Mol. Sci. 2026, 27, 761. [] [ CrossRef] Nguyen, N.H.; Lee, Y.I.; Kim, Y.J.; Lee, H.; Kim, J.; Lee, J.H. Translational Evaluation of a Disodium Adenosine Monophosphate (AMP2Na)-Based Topical Formulation for Physiology-Aligned Skin Rejuvenation: Integrated In Vitro, Ex Vivo, and Clinical Evidence. Int. J. Mol. Sci. 2026, 27, 4840. [] [ CrossRef] Charan, J.; Kantharia, N.D. How to calculate sample size in animal studies? J. Pharmacol. Pharmacother. 2013, 4, 303–306. [] [ CrossRef] [ PubMed] Suckow, M.A.; Fallon, M.T. The ARRIVE 2.0 Guidelines: Importance and Full Adoption by AALAS Journals. Comp. Med. 2024, 74, 307–312. [] [ CrossRef] Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. © 2026 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license. Share and Cite Roh, H.; Lee, Y.I.; Jung, J.; Nguyen, N.H.; Hwang, J.K.; Kim, J. Innovative Facial Contouring Using a Monopolar Radiofrequency Device with Continuous Water Cooling: An Integrated Clinical and Preclinical Study. Int. J. Mol. Sci. 2026, 27, 5162. https://doi.org/10.3390/ijms27125162 Roh H, Lee YI, Jung J, Nguyen NH, Hwang JK, Kim J. Innovative Facial Contouring Using a Monopolar Radiofrequency Device with Continuous Water Cooling: An Integrated Clinical and Preclinical Study. International Journal of Molecular Sciences. 2026; 27(12):5162. https://doi.org/10.3390/ijms27125162 Roh, Hyojin, Young In Lee, Jinyoung Jung, Ngoc Ha Nguyen, Jewan Kaiser Hwang, and Jihee Kim. 2026. "Innovative Facial Contouring Using a Monopolar Radiofrequency Device with Continuous Water Cooling: An Integrated Clinical and Preclinical Study" International Journal of Molecular Sciences 27, no. 12: 5162. https://doi.org/10.3390/ijms27125162 Roh, H., Lee, Y. I., Jung, J., Nguyen, N. H., Hwang, J. K., & Kim, J. (2026). Innovative Facial Contouring Using a Monopolar Radiofrequency Device with Continuous Water Cooling: An Integrated Clinical and Preclinical Study. International Journal of Molecular Sciences, 27(12), 5162. https://doi.org/10.3390/ijms27125162 Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details . Article Metrics Article metric data becomes available approximately 24 hours after publication online.
