Radiofrequency and pulsed electromagnetic field application following liposuction—Clinical evaluation of performance and safety

With more than 1.5 million performed procedures, liposuction was the second most performed esthetic surgical procedure all over the world in males and in females in the year 2020. The objective of this open‐label, evaluator‐blinded study was to assess the efficacy and safety of an energy‐based device that combines multipolar radiofrequency with pulsed electromagnetic field (PEMF) in patients that underwent liposuction.


| INTRODUC TI ON
][10][11] As the already lax tissue is depleted of its superficial and deep subcutaneous fat, the organizational and structural properties of the superficial fascial system are reduced by the liposuction procedure, which results in further increased laxity of the excess skin. 7,12The use of radiofrequency-based devices might allow to target increased skin laxity after liposuction by inducing a tightening of the skin via collagen contraction and remodeling.4][15] This remodeling of collagen structures further facilitates skin tightening. 8RF can be paired with pulsed electromagnetic field (PEMF) to further fortify the radiofrequency-induced collagen synthesis.PEMF offers nonthermal stimulation to the skin and induces the release of fibroblast growth factor-2, which promotes collagen synthesis, further contributing to skin tightening. 16,17The use of tightening devices using RF and PEMF after liposuction to fight skin laxity seems promising; however, objective data are limited.Thus, the objective of this open-label, evaluatorblinded study was to assess the efficacy and safety of a novel noninvasive multipolar RF energy-based device with PEMF in patients that underwent liposuction.

| Trial design
This investigation was a prospective, open-label, evaluatorblinded study.The study was conducted between February 2018 and November 2020 at Ocean Clinic, Marbella, Spain.This study was registered in the Clini calTr ials.govRegistry (ID number: NCT03588702).All subjects provided written informed consent to participate in the trial.

| Participants
Eligibility criteria for participants are given in Tables 1 and 2.

| Intervention
Subjects received a total of six study treatments at 1-week intervals to one side of their body (flanks and/or thighs), which was treated with liposuction 8 weeks prior to inclusion of the study.The side to be treated was left to the discretion of the investigator in consultation with the subject.All subjects underwent bilateral liposuction.
The same side was treated at each treatment visit with the treatment parameters specific to the subject documented.A thin layer of medical-grade glycerin was applied to the treatment area.Afterward, the treatment with the Venus Legacy system (Venus Legacy) using the LB2 body applicator was performed.The treatment time was set at 30 min, the internal electrode energy at 50% and the output energy between 50% and 100%, as high as the subject could tolerate.
The treatment size was 21 × 29 cm.

| Subjective assessment
Subjects were followed up at 1 month after their last treatment.
Assessments were conducted with clinical photography, taken with standardized photography equipment, including stool height and anatomical alignment, illumination, and background throughout the study.Clinical photographs of the treatment area were taken at pretreatment and 1-month postfinal treatment.The primary endpoint was the improvement in skin appearance of flanks and thighs at 1month post-treatment compared with baseline as assessed by three blinded evaluators by photographic assessment utilizing the global aesthetic improvement scale (GAIS).The used GAIS was a 5-point scale ranging from −1 (worse) to 3 (very much improved).Subjects' assessments of overall satisfaction with the treatment were performed using a subject satisfaction scale (SSS) at 1-month postfinal treatment.The SSS was a 5-point scale ranging from 0 (very TA B L E 1 Inclusion criteria of this investigation.

Inclusion criteria
Able to read, understand, and voluntarily provide written informed consent Healthy male or female older than 18 years of age but not older than 65 years of age Having suitable area for treatment (bilateral liposuction of the arm, thighs or flanks performed 8 weeks prior to the study) BMI score is greater than 18.5 and less than 29.9 Willingness to follow the treatment and follow-up schedule and the post-treatment care Willingness to refrain from a change in diet/drinking/exercise/ medication regimen for the entire course of the study For female of childbearing potential-using a medically acceptable form of birth control at least 3 months prior to enrollment and during the entire course of the study (i.e., oral contraceptives, IUD, contraceptive implant, barrier methods with spermicide, or abstinence), and have a negative urine pregnancy test at baseline unsatisfied) to 4 (very satisfied).Moreover, subjects were asked to note down their discomfort and pain after study treatment as measured using a 10 cm visual analog scale.

| Cutometer measurements
Cutometer dual MPA 580 (Courage+Khazaka electronic GmbH) was used to assess the skin firmness (R0 parameter), visco-elasticity (R2 parameter), and net elasticity (R5 parameter) at baseline and 1 month after last study treatment.In brief, a 4-mm-diameter measuring probe was applied at a constant suction of 400 mbar for 3 s, followed by a relaxation time of 2 s, for 3 repetitions.For consistency purposes, the same investigator (K.K.) performed the Cutometer® measurements at the same location under the same circumstances.

| Safety assessment
Safety was evaluated by assessing the frequency, severity, and causal relationship of adverse events (AEs), serious AEs, and AEs of special interest during the entire study period.

| Statistical analyses
The data were normally distributed, as assessed by Shapiro-Wilk's test (p > 0.05).One-sided Student's paired t-test was used to test for differences between the treated and sides at baseline and follow-up.One-sided Student's paired t-test was used to test for differences between baseline and follow-up for the treated and untreated sides, separately.All calculations were performed using SPSS Statistics 26 (IBM), and results were considered statistically significant at a probability level of ≤0.05 to guide conclusions.

| Subject disposition and demographics
A total of 30 subjects, of whom 24 were females (80%), were enrolled in this investigation.The mean age was of 48.

| Subjective assessment
Three independent and blinded reviewers rated the improvement of the treated side on average with 1.17 + 0.07 (between improved and much improved) compared with baseline.Subjects were very satisfied with their treatment, with a mean score of 3.24 (0.03) out of 4 at the 1-month follow-up visit.A total of 28 subjects (93.3%) were either satisfied or very satisfied, while only two subjects (6.6%) were TA B L E 2 Exclusion criteria of this investigation.As per the Investigator's discretion, any physical or mental condition which might make it unsafe for the subject to participate in this study dissatisfied (Figures 1 and 2).The overall pain experienced (mean from all six treatments) using the VAS was 0.66 ± 0.03 cm out of 10 cm on the VAS, which correlates to "mild pain" and is very close to "no pain."Sixty-seven percent of the patients reported mild pain, while 33.3% reported no pain at all.

| Safety assessment
No treatment-related AEs were observed during the study period.

| DISCUSS ION
This study investigated the efficacy and safety of applied RF and PEMF after liposuction of the thighs and flanks.The results revealed that overall, a very high patient satisfaction was reported, while at the same time, independent, blinded reviewers rated the esthetic appearance as improved.(Figures 3-5) Cutometer measurements did not reveal any significant differences of skin firmness, skin visco elasticity and net elasticity between treated and untreated sides at follow-up.
Skin elasticity is influenced by the architecture of the superficial fascial system, composed of the superficial fatty layer, superficial fascia, deep fatty layer and deep fascia and fibers that connect the fascias with each other and the skin, comparable to a honeycomb. 7,12,18posuction aims to reduce the superficial and deep fatty layer, while at the same time the integrity of the superficial fascial system is damaged, as the liposuction probe penetrates the fascial arrangement. 7,12,18This may create a weakened superficial fascial system, resulting in increased skin laxity and decreased skin firmness, as the stabilizing fibrous arrangement is damaged.Furthermore, it can be argued that the depleted superficial and deep fatty layer cannot support the already weakened fascial arrangement anymore.Clinically, this is observed as local and regional skin excess and increased mobility of the skin, often resulting in rippling and contour irregularities.
RF creates local heat, which denatures the collagen fibers of the superficial fascial system.Upon denaturation of the collagen, the fibers transition from their elongated helical arrangement into a condensed arrangement. 19,20This strengthens the connection between the deep and superficial fascia and the skin and can be considered as a curative way to tackle the disintegrated superficial fascial system after liposuction.Furthermore, the locally applied thermal and nonthermal energy This study is not free of limitations.As mentioned, the follow-up period after termination of the treatment could have been lengthened to assess the long-term potential of skin tightening and patient satisfaction.Also, ultrasound measurements might have revealed insights into the change in the superficial fascial system. 21A previous report has shown that ultrasound allows for a quantification of the stability of the superficial fascial system, which might have been a useful outcome measurement in this investigation.
However, to the knowledge of the authors this is the first investigation that assessed RF and application of PEMF impact after liposuction in a subjective and also objective manner.

| CON CLUS ION
There is a plethora of claims about skin tightening, skin repositioning, and slimming properties of devices, which might attract pa- 4 ± 11.0 years (range: 27-69 years), and the mean weight was 69.5 ± 11.7 kg.All of the subjects were Caucasian, of which 12 presented with a Fitzpatrick skin type II, 15 with a Fitzpatrick skin type III, and 3 with a Fitzpatrick skin type IV.Twenty-one of the patients received a treatment at the flank, while nine received the treatment at the thigh.
Exclusion criteria Pregnant or planning to become pregnant, having given birth (vaginal birth or Cesarean surgery) less than 9 months ago, and/ or breastfeeding Having any active electrical implant anywhere in the body, such as a pacemaker or an internal defibrillator Having a permanent implant in the treated areas, such as metal plates and screws or an injected chemical substance Having undergone any other surgery in the treated areas within 9 months of treatment or during the study Having or undergoing any form of treatment for active cancer, or having a history of skin cancer or any other cancer in the areas to be treated, including the presence of malignant or premalignant pigmented lesions Suffering from significant concurrent illness, such as cardiac disorders, diabetes (type I or II), lupus, porphyria, or pertinent neurological disorders Having a known anticoagulative or thromboembolic condition or taking anticoagulation medications 1 week prior to and during the treatment course (to allow inclusion, temporary cessation of anticoagulant use as per the subject's physician discretion is permitted) History of immunosuppression/immune deficiency disorders (including HIV infection or AIDS) or currently using immunosuppressive medications Suffering from hormonal imbalance which may affect weight or cellulite, as per the Investigator's discretion History of significant lymphatic drainage problems Suffering from significant skin conditions in the treated areas or inflammatory skin conditions, including, but not limited to, open lacerations or abrasions and active cold sores or herpes sores prior to treatment (duration of resolution as per the Investigator's discretion) or during the treatment course History of keloid scarring or of abnormal wound healing History of being especially prone to bruising History of epidermal or dermal disorders (particularly if involving collagen or micro-vascularity) Use of isotretinoin (Accutane®) within 6 months of treatment or during the study Use of anticellulite creams within a month of treatment or during the course of the study If any allergy that is related to the glycerin used in this study appears, subjects may be excluded from the study Significant change in diet or exercise regimen within a month of enrollment or during this study and/or weight loss or gain of 10 lbs (4.5 kgs) within 2 months of enrollment or during this study Participation in a study of another device or drug within 1 month prior to enrollment or during this study

3. 3 |
Cutometer measurements3.3.1 | FlanksAt baseline, the treated side and untreated side presented with no significantly different elasticity.The treated side had a mean elasticity of 0.47 ± 0.1 mm, while the untreated side had a mean elasticity of 0.47 ± 0.1 mm with p = 0.440.At follow-up, the mean elasticity of the treated side was 0.50 ± 0.1 mm, while the untreated side had a mean elasticity of 0.40 ± 0.1 mm with p = 0.246.No significant difference in the elasticity was obtained between baseline and follow-up for both, treated and untreated sides.At baseline, the visco-elasticity was 84.2% ± 8.1% on the treated side and 81.3% ± 9.6% on the untreated side with p = 0.117.At follow-up, the mean visco-elasticity was 85.1% ± 6.7% on the treated side and 84.6% ± 7.6% on the untreated side with p = 0.379.No significant difference in the viscoelasticity was obtained between baseline and follow-up for both, treated and untreated sides.Net elasticity was 66.6% ± 9.9% and 65.5% ± 14.4% on the treated and untreated sides at baseline, respectively (p = 0.345).At follow-up, net elasticity was 65.5% ± 13.7% and 66.1% ± 14.9% on the treated and untreated sides, respectively (p = 0.447).No significant difference in net elasticity was obtained between baseline and follow-up for the treated and untreated sides.

3. 3 . 2 |
ThighsAt baseline, the treated side had a mean elasticity of 0.47 ± 0.1 mm, while the untreated side had a mean elasticity of 0.47 ± 0.1 mm with p = 0.480 At follow-up, the mean elasticity of the treated side was 0.47 ± 0.1 mm, while the untreated side had a mean elasticity of 0.50 ± 0.1 mm with p = 0.230.No significant difference in the elasticity was obtained between baseline and follow-up for both, treated and untreated sides.At baseline, the visco-elasticity was 84.7% ± 10.9% on the treated side and 83.0% ± 10.1% on F I G U R E 1 Stacked bar graph showing the percentage of subjects score using the global aesthetic improvement scale at 1-month follow-up, as graded by three independent graders.F I G U R E 2 Stacked bar graph showing the percentage of subjects reporting satisfaction using the subject satisfaction scale at 1-month follow-up.the untreated side with p = 0.243.At follow-up, the mean viscoelasticity was 89.1% ± 4.4% on the treated side and 87.9% ± 8.9% on the untreated side with p = 0.345.No significant difference in the visco-elasticity was obtained between baseline and follow-up for both, treated and untreated sides.Net elasticity was 76.2% ± 20.7% and 70.4% ± 19.1% on the treated and untreated sides at baseline, respectively (p = 0.102).At follow-up, net elasticity was 70.8% ± 15.3% and 71.4% ± 18.0% on the treated and untreated sides, respectively (p = 0.463).No significant difference of net elasticity was obtained between baseline and follow-up for the treated and untreated sides.

E 3 F I G U R E 5
Female patient 8 weeks after liposuction at the flanks prior to treatment.F I G U R E 4 Female shown in Figure 3 4 weeks after six treatments at the left flank with the investigated device.Female patient after six treatments at the left thigh with the investigated device.stimulatescollagen synthesis of fibroblasts in a three-dimensional manner due to the upregulation of sirtuin genes, which again strengthens the superficial fascial system.The PEMF which has been used in synergy with the radiofrequency in this investigation causes a change in the electrical potential of receptors located on the membrane of dermal cells, which downstream triggers molecular and cellular reactions.PEMF therapy has shown to significantly increase collagen fiber synthesis in fibroblasts shortly after application, which again supports the weakened superficial fascial system.19Interestingly, the cutometer measurements did not show any statistically significant changes in the elasticity, visco elasticity or net elasticity of the skin.The probe of the used cutometer has an opening of 4 mm.A vacuum with a steady negative pressure is created and the skin is pulled into the opening, where a light diode measures the retraction of the skin.If the skin is firmer, that is, less elastic, less skin is pulled into the cutometer opening, which is reflected by a smaller depth of penetration of the skin.Based on the proposed mechanism of restoration of the superficial fascial system and consecutive skin tightening using RF and creation of PEMF, less skin should have been pulled into the opening as its elasticity decreased and firmness increased.A potential explanation for any significant differences in biomechanic properties of the skin could be the relatively short follow-up period after application of the RF and PEMF.The formation of new collagen takes weeks to months, and the full effect of the treatment might thus be observed at a later point than 4 weeks after the last treatment.Furthermore, the skin is pulled into an opening which has a diameter of 4 mm.It could be argued that the biomechanical changes of the skin cannot be recorded in such a small area of interest.Potentially, the use of a traditional skin caliper might have provided more useful insights into the influence of radiofrequency and application of a PEMF on skin tightening.Even though it might be argued that due to the lack of significant cutometer findings RF/PEMF cannot provide skin tightening, it should be noted that clinically, an improved appearance of the treated areas has been noted by three experienced independent reviewers.The clinically convincing results (Figures6 and 7) support the idea that cutometer measurements which assess biomechanic properties of the skin in an area of interest with a diameter of 4 mm might not be able to capture the overall change in biomechanical stability of the superficial fascial system, which has been created by the treatment.Moreover, the subject reported high level of satisfaction with the treatment further supports this view.

F I G U R E 7
tients and influence their decision on a particular treatment for skin tightening.While surgical techniques and minimally invasive treatments, especially energy-based devices, have been refined in the last decades, it is the responsibility of surgeons to validate the results of the created techniques and minimally invasive treatments in an objective way, in order to strengthen the scientific foundation of esthetic surgery.This study has revealed that the subjective satisfaction of RF/PEMF after liposuction is high and the esthetic F I G U R E 6 Male patient 8 weeks after liposuction at the flanks prior to treatment.Male shown in Figure 6 4 weeks after six treatments at the left flank (black arrows) with the investigated device.