Efficacy and safety of a noninvasive, home‐based radiofrequency device for facial rejuvenation: An open‐label, intraindividual controlled trial

Wrinkle formation is the most visible characteristic of facial aging. Radiofrequency (RF) technology is currently utilized to reduce facial wrinkles and contribute to skin rejuvenation.


| INTRODUC TI ON
Facial skin aging is manifested as wrinkle formation, dilated pores, loss of elasticity, and thinning of the skin.These changes are associated with reduced collagen synthesis and decreased concentration of dermal elastin. 1 In recent years, the growing expectancy of appearance brought about an increasing demand for facial cosmetic technologies.Therapies for facial rejuvenation involve the use of topical agents such as antioxidants and acid products; besides, energy-based technologies have been widely applied to promote collagen remodeling for preventing facial aging. 2,3During the past decade, minimal invasive therapies 4 have increased in popularity among Chinese patients.Although ablative fractional lasers remain the first-line approach for skin resurfacing, their use is usually followed by a prolonged recovery time and unpleasant posttreatment complications including scar formation, pigmentation, and infection, 5 especially for Asian individuals with Fitzpatrick skin type III-IV. 6diofrequency (RF) technology, based on its biothermal effect that triggers the remodeling and regeneration of collagen, has recently gained popularity in the treatment of skin laxity, atrophic scar, and acne scar. 7,81][12] Accordingly, the effectiveness and safety of home-use RF devices have also been the focus of attention.This prospective study is conducted to analyze the efficacy and safety of a noninvasive, home-based RF device applied for facial rejuvenation in Chinese people.

| Design and subjects
This was a single-center, open-label, intraindividual controlled trial.
The purpose of this study was to investigate the effect of a portable radiofrequency device ABF202 (AMIRO, China) for the improvement of facial skin appearance.A total of 22 healthy female individuals aged 25 to 60 years with Fitzpatrick skin type III-IV, who were willing to complete four times of follow-up visits and had mild to moderate facial wrinkles (Fitzpatrick Wrinkle Classification Scale [FWCS] 1-6 13 ) were enrolled in our trial.The exclusion criteria included allergy to ultrasound coupler, pregnancy, any implantable electronic device, or any active skin infection on the face.All subjects had signed the informed consent form.

| Treatment device and protocol
A home-based multipolar RF device ABF202 (AMIRO, Shenzhen, China, Figure 1) was adopted for the trial.This noninvasive device gently delivers RF energy at controlled depth to the dermis with a grid of 19 internally installed electrodes that generate electric current through the skin and heat the tissues to induce immediate collagen contraction.
The treatment surface is equipped with a temperature sensor, which allows real-time thermal control to avoid epidermal injury.
Two types of modes are available when used for skin tightening: the deep mode and the daily mode.In a deep mode session, a face peel with gridlines (AMIRO BEAUTY) is firstly applied to protect the skin, and the treatment surface is put on top of the peel to provide optimal energy (5.22-6.25 W) for each section divided by the gridlines, with the higher energy (5.75-6.25 W) applied to the lower half of the face.In a daily mode session, conductive gel is used to facilitate RF energy transduction.All subjects were required to complete a deep mode session followed by a daily mode session three times a week for an 8-week treatment.During the study period, subjects were instructed to use the same skin care products including gentle cleanser and sunscreen cream as they used before.

| Clinical assessment and study endpoints
Treatment area was assessed in a constant environment (temperature 20-22°C, humidity 40%-60%) at baseline and 2 weeks, 4 weeks, and 8 weeks after treatment.Two investigators independently evaluated wrinkles of cheek, middle face, periorbital area, and nasolabial groove using the FWCS score (1-3: fine wrinkles; 4-6: fine to moderate depth wrinkles, moderate number of lines). 13Furthermore, a blinded assessment of all subjects' pictures in a randomized order with the FWCS score was conducted at the end of our study by another three evaluators.Subjects were asked to score their overall satisfaction with a 10-point VAS (0-2 "no improvement," 3-5 "mild improvement," 6-8 "obvious improvement," and 9-10 "great improvement") at each visit.The DermaLab Combo system coupled F I G U R E 1 Home-based multipolar RF device ABF202 (AMIRO) adopted for the study.
with a skin ultrasound probe was applied to measure the density and thickness of dermal layer on the midfacial area.We used the Meitueve 3D skin analysis system (Meitu, China) to evaluate the length, density, and proportion of facial wrinkles in different site.This system is equipped with a high-resolution camera that takes standard digital photographs of individuals using the multispectral imaging technique and a computerized image analysis system that provides measurement of facial wrinkles, fine lines, and pores using the 3D reconstruction images.
The primary endpoint was the improvement on FWCS scores assessed by the blinded evaluators after 4 weeks of treatment as compared to baseline.The secondary endpoints were the improvement on FWCS scores assessed by the blinded evaluators and the increase in dermal thickness of midfacial skin after 8 weeks of treatment as compared to baseline.Any adverse event occurred during the treatment was recorded to assess the safety of this device.

| Statistical analysis
Statistical analysis was performed using a paired t test with SPSS 23.0.Continuous variables were described by mean and standard deviation, and categorical variables by count and percentage.
Statistical significance was defined as p < 0.05.The results of open-label assessments during the treatment period also revealed obvious reduction in FWCS scores at week 4 and week 8 as compared to the baseline (Figure S1).

| Improvement of dermal thickness by skin ultrasound
Skin ultrasound images of the same zone on the midfacial area of all subjects were obtained using the DermaLab Combo system.As representative images shown in Figure 4, the thickness of dermal layer was gradually improved a little bit during the follow-up.Moreover, the quantitative outcomes of all subjects revealed an increase of the dermal thickness at week 8 (1131.7 ± 341.0 vs 911.1 ± 222.2 μm, p < 0.05) as compared to the baseline (Table 1).

| Improvement of facial aging by the 3D skin analysis system
The proportion, density, and length of wrinkles in different facial area evaluated by the Meitueve 3D skin analysis system at each

TA B L E 1
The thickness and density of dermal layer on the midfacial area before and after treatment.timepoint were summarized in Table 2.A significant decrease in the proportion and density of perioral wrinkles was observed at week 4 as compared to the baseline (0.37 ± 0.26 vs 0.45 ± 0.36, 0.030 ± 0.020 vs 0.035 ± 0.027, respectively, p < 0.05; Table 2).

Baseline
The proportion, density and total length of bilateral nasolabial grooves had a tendency to decrease from baseline to week 4 as displayed in Table 2 (p > 0.05).In addition, there was no significant improvement in the proportion and density of periorbital wrinkles at week 4 or week 8.

| Subject report outcome
Subject report outcome was obtained using overall satisfaction of subject with a 10-point VAS at week 2, week 4, and week 8. 12 (54.5%)subjects reported obvious improvement at week 4, and 14 (63.6%) subjects reported obvious or great improvement at week 8.All subjects reported improvement with different degrees after 8 weeks of treatment (Figure 5).

| Safety and adverse effects
The treatment procedure was well-tolerated and no serious adverse event were observed during the 8-week period.None of the subjects reported significant discomfort when using the device.Only one subject reported mild erythema without pruritus 1 week after starting treatment, and the erythema was eliminated 2 days after ice compress.No hyperpigmentation or any other adverse event occurred in her subsequent treatment (Table 3).

| DISCUSS ION
Features of facial aging include the formation of wrinkles and folds, decreased skin thickness, poor skin texture, and hyperpigmentation. 14Among the various factors related to aging process, the degradation of elastin network and collagen bundles in the dermis highly contributes to wrinkling and thinning of skin. 1 RF technology is emerging as a promising therapy for facial rejuvenation in recent years.Noninvasive RF devices deliver electric current to the dermis to induce thermal injury and immediate contraction of collagen fibers while sparing the epidermis.The thermal damage of tissue induced by the RF energy leads to a wound-healing process that is associated with sustained collagen proliferation and remodeling, with minimal impact on the epidermal melanin. 15,16stological evidence revealed that no obvious inflammatory infiltrate or necrosis was present in the biopsy samples from animal models after 14 days of RF treatment. 17In this way, noninvasive RF technology is considered to be an appropriate approach that can enhance facial elasticity with mild adverse reactions for all skin types.
Previous clinical studies have demonstrated the facial rejuvenated effect of various noninvasive RF systems involving the monopolar RF, 18 bipolar RF, 10 and multipolar RF. 12 While most of these RF systems were traditionally used by dermatologists, the treatment procedures required frequent visits from patients and expensive cost.Therefore, taking the advantages of convenience and cost-effectiveness, home-use RF devices have gradually increased in popularity among customers. 19A 12-week intraindividual controlled study on home-use RF device demonstrated significant wrinkle reduction and lift effect of the lower face after treatment, and the treating procedure was painless. 20Moreover, a split-face randomized clinical trial showed significant increase in skin thickness of the participants after they using a bipolar home-based RF device for 12 weeks. 21These findings are similar to our results.However, our current study showed that a multipolar RF device could have a therapeutic effect on skin aging in a relatively short treatment period.
Compared with the other home-use devices in previous trials, [20][21][22] this novel RF device emitted lower energy (6.25 W) to the dermis through an array of 19 electrodes, heating the tissues with relatively less risk of complications.Besides, we used a noninvasive method for dermal thickness detection to generally reflect the change of tissue structure in dermis.
In the present study, we demonstrated that 8 weeks of treatment at a frequency of three times per week using a noninvasive, homebased RF device significantly improved skin wrinkles and thickness, and contributed to facial rejuvenation.The extent of improvement on FWCS scores showed statistical significance after 4 weeks of treatment and gradually increased with the extending of treatment period (Figure 2).The treatment procedure was well-tolerated, and only one subject reported mild erythema that subsided in 2 days.
These results indicated that the device was effective in improving skin texture and elasticity in a safe pattern.Moreover, assessment of skin texture with 3D analysis system showed great improvement in perioral wrinkles rather than the others at week 4 (Table 2), which may be attribute to higher energy settings on lower half of the face.
The difference between the subjective and objective outcomes may result from the detection of subtle changes by the high-resolution camera used for objective assessments.Subjects in our study were generally satisfied with the efficacy of the device.In the future, as the demand for facial rejuvenation increased, home-use RF techniques can be a promising antiaging method, while the efficacy and safety of them need to be further explored.
There are several limitations of our study.This is an open-label, single-arm intra-individual controlled trial with small samples.
Studies in a larger sample and a longer follow-up period are warranted to confirm the results.In addition, the parameters of the Meitueve 3D skin analysis system need to be further explored.

PH OTO CO N S E NT S TATE M E NT
All subjects had approved the use of their photos for the study.

E 2
The change in FWCS scores of wrinkles on cheek, middle face, periorbital area, and nasolabial groove between baseline and follow-up visits as assessed by blinded evaluators.Bars represent standard deviation; *p < 0.05.**p < 0.005.F I G U R E 3 Representative photos of perioral wrinkles (A, B) and periorbital wrinkles (C, D) at baseline (A, C) and 8 weeks (B, D) after treatment.F I G U R E 4 Representative ultrasound images of midfacial skin from a 42-year-old subject at baseline (A), and 2 weeks (B), 4 weeks (C) and 8 weeks (D) after treatment.
AUTH O R CO NTR I B UTI O N SXuechen Ai and Liuyu Chen performed the subjective evaluation and the skin ultrasound.Yu Lan and Ben Liu took the photos of subjects and operated the skin analysis system.Pengfei Song, Zhenying Zhang, and Jing Wang conducted the blinded assessment.Xuechen Ai and Pengfei Song analyzed the statistics.Zhenying Zhang and Jing Wang designed the study.Xuechen Ai and Zhenying Zhang wrote the paper.E TH I C S S TATEM ENT This study was approved by the Medical Ethics Committee of The Eighth Affiliated Hospital, Sun Yat-sen University (ZB-KYIRB-AF/ SC-08/01.0) in August 2022.All subjects in the study had signed the informed consent form.The authors confirm that the ethical policies of the journal, as noted on the journal's author guidelines page, have been adhered to and the appropriate ethical review committee approval has been received.The US National Research Council's guidelines for the Care and Use of Laboratory Animals were followed.
The proportion, density and length of wrinkles in different facial area.
The p-values less than 0.05 are highlighted in bold.