A review of research for a cryolipolysis technology

Obesity and excess body fat are known health issues and a major aesthetic concern. Numerous modalities have been developed to address unwanted deposits of adiposity, including the development of various noninvasive methods overcoming the limitations and risks of invasive alternatives. Cryoadipolysis, also known commonly as cryolipolysis, involves the harnessing of selective cryolysis, the selective cold‐based damaging of subcutaneous fat cells which die via apoptosis, and are removed naturally by the body over time.

theorized that the lack of inflammatory response indicated that fat cell death via apoptosis, followed by the natural removal of dead fat cells by the body after treatment, was responsible for fat reduction.
In 2012 Ferraro, et al. 4 demonstrated that while a small percentage of cells die by necrosis, the majority of affected cells die via apoptosis.Scientific review of the literature has strengthened the support for the overall technology 1

| APPLI C ATOR S AND TRE ATMENT
Applicators for the Cooltech and Cooltech Define devices use vacuum suction to isolate and compress the fat fold to be treated, to ensure maximum exposure of adipose tissue in the treatment zone, and simultaneously promote local ischemia to mitigate potential heating from circulating blood.Before treatment, skin in the treatment area is coated in a cryoprotectant gel to prevent formation of ice and subsequent untoward freezing damage.A patented Cool Gel Pad (a cellulose membrane embedded in glycerin and other cryoprotectant ingredients 6 ) is mandatory for the treatment further protects the skin and is placed in the treatment area before application of handpieces.
With the Cooltech device, tissue is drawn between parallel anodized aluminum cooling plates in each of six available applicators, two of which can be used simultaneously in a single session.Applicators are designed for specific areas of the body and differ in cavity volume, cooling surface, and cavity depth. 7During treatment, Cooltech applicators operate at −8°C; evaluation of the Cooltech handpieces 7 showed that even over the course of a 70-min treatment session, the temperature remained less than 0°C which is below various established possible targets to ensure adipocyte crystallization.Skin tissue remains undamaged.Figures 3 and 4 provide examples of results using the Cooltech device.
In the case of Cooltech Define, 8,9 each of nine available applicators rely on larger volume concave applicators (termed "360° A single center study by Fajardo Urdiales, et al. 6 included patients (n = 8, six women, mean age of 44 ± 9.17 years, mean BMI 26.88 ± 2.38) with localized fat in the abdomen and flanks.
Cryolipolysis with the Cooltech device was administered to four areas in total (two for the abdomen and one on each flank) all applications in same day session using the Straight HP applicator, cooled to −8°C with suction at 220 mbar for 70 min.
Outcomes were based on before-and-after evaluation using bioimpedance measurements, ultrasound, photography, and body circumference measurement.Follow up occurred at weeks 4 and 8 after treatment.All patients experienced circumference reduction.
Ultrasound results showed a mean thickness decrease of 15.34%

| P OTENTIAL S IDE EFFEC TS
Common side effects after cryolipolysis include bruising, erythema, pain, sensitivity, and swelling, all of which resolve within a few weeks at most.
and shown consistently high patient satisfaction.A variety of devices harnessing this concept have been marketed since.This cryolipolysis device technology discussed here (Cooltech® and Cooltech® Define, Sinclair) is a safe, noninvasive modality for reducing unwanted fat.The CoolTech and CoolTech Define platforms are shown in Figures 1 and 2, respectively.As with all devices relying on the principle of selective cryolysis, these devices 5 use specially designed applicators to bring the temperature of an area down to a predetermined therapeutic level and maintain it for a given length of time, to induce cold panniculitis and apoptosis of fat cells in the target area without damage to overlying skin and tissue.Treatment is well tolerated with mostly transient side effects.The body naturally eliminates the cellular contents and debris over time, reshaping the treated region.As with most aesthetic body contouring devices, these are indicated for patients of normal weight or slight overweight.These devices are currently not marketed or available in North America.The purpose of this study is to provide a brief but comprehensive overview of the literature and respective findings examining these devices for cryolipolysis.
cooling technology"), enhancing results by delivering more comprehensive coverage to the targeted treatment area.Up to four areas can be treated in a single session.During treatment Cooltech Define operates at a range of −8°C to −10°C, causing crystallization of adipocytes.Evaluation of the Cooltech Define handpieces 8,9 showed superior homogeneous cooling overall when comparted to Cooltech handpieces, as well as faster time to target temperature, reducing treatment times over those of the Cooltech device.Cooltech Define includes the creation of the "Smart Contact" Cool Gel Pad, which features enhanced cryoprotection as well as an RFID system that triggers the treatment when the authorized membrane is applied.This enables the provision of safer treatments to patients.Each Cool Gel Pad must be used individually and for each treatment area to ensure proper protection during the treatment.Skin tissue remains undamaged.Treatment comfort partially depends on natural hypoesthesia of the skin due to cold.This occurs more rapidly with the Cooltech Define applicators, 8,9 thus treatment is more comfortable for the patient.Vacuum suction with Cooltech Define handpieces is also gentler, 9 further improving patient comfort.Figures 5 and 6 provide examples of outcomes obtained using Cooltech Define platform.An adjusted physics model was used in numerous studies of these technologies to validate the operation and effect of the Cooltech and Cooltech Define devices. 7-11In each study, COMSOL Multiphysics simulation software (COMSOL) was employed to model the physics of heat exchange between treated tissue and different handpiece configurations to determine cooling characteristics.This method was validated through specific investigation 10 involving F I G U R E 1 The CoolTech platform.use of the Cooltech handpieces for known substances (olive oil and water) which favorably compared with the simulation model.3 | SAFE T Y AND EFFI C AC Y Overall, research evaluating the safety and efficacy of the Cooltech and Cooltech Define devices has shown significant reduction in fat thickness and circumference in treated areas.Vélez González, et al. 12 evaluated cryoadipolysis in patients (n = 15, 11 women, average age 42 ± 15 years) with localized fatty deposits in the abdomen and/or flanks.None were significantly overweight, according to study doctors.Subjects were treated with a single session using the Cooltech Straight HP applicator, cooled to −8°C with suction at 235 mbar for 70 min; a coupler was fitted to reduce the treatment area in some cases to accommodate smaller treatment areas.A pulsed magnetic field device and topical corticosteroids were also used immediately after treatment to mitigate inflammation and edema.Assessment of results consisted of photography, circumference measurements, skin fold caliper measurements of cutaneous folds.Reduction in abdominal skin fold measurement averaged 19.6% (±8.50), and circumference measurements averaged 2.33 cm (±3.13).Some pain at the beginning and in the end of treatment was noted in the majority of cases, and all patients experienced temporary reduction in sensation of the treatment area which resolved within 21 days after treatment.

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±13.32) in the abdomen and 11.03% (±25.21) and 4.57% (±25.68) in the right and left flanks, respectively.Biopsy revealed adipocyte death without sign of necrosis or residual inflammation.High patient satisfaction was recorded as well.No major adverse events were recorded; all patients experienced some erythema and edema, with F I G U R E 2 The CoolTech Define platform.F I G U R E 3 Side view of a male patient before (left) and after (right) a course of treatment to the lower abdomen with CoolTech using the Straight HP handpiece.
three patients experiencing mild to moderate pain sensation that subsided within 24 h, and five patients experienced paresthesia lasting approximately 1 week.A 2019 evaluation of Cooltech Define by Viera Mármol and colleagues 9 included 23 patients (17 women, mean age 38 ± 10.41 years) given a single session of up to four applicators (−10°C for 70 min for large applicators, −5°C for 45 min for small applicators), resulting in 69 total areas treated.After treatment, each area was immediately given gentle massage for 2-5 min.Average skin fold reduction over all 69 areas was 7.80 mm (±3.46) which, notedly, included both large and small treatment areas.Average circumference reduction for all subjects was 32.2 mm (±1.86) with the largest reduction measured as 80 mm.All side effects were reportedly mild, resolving quickly and without sequelae.Satisfaction was reportedly high for all subjects.

F I G U R E 4
Side view of a female patient before (left) and after (right) a course of treatment to submentum with CoolTech using the Tiny HP handpiece.F I G U R E 5Rear view of a female patient before (left) and at 4 months after (right) a course of treatment with CoolTech Define.Treatment includes two sessions using the Oval HP applicator to the inner thighs and one session to the flanks, one session each using the Straight HP applicator to the arms and infrascapular region, one session under the buttocks ("banana rolls") using the Curved HP handpiece, and one session using the Tuny Curved HP applicator to the inner knees.E TH I C S S TATEM ENT Cooltech® and Cooltech® Define are CE-marked devices.O RCI D Michael H. Gold https://orcid.org/0000-0002-5183-5433R E FE R E N C E S