Safety and Efficacy of Diluted Calcium Hydroxylapatite for the Treatment of Cellulite Dimpling on the Buttocks: Results from an Open-Label, Investigator-Initiated, Single-Center, Prospective Clinical Study.

BACKGROUND: Cellulite is a condition characterized by dimpling and contour irregularities in the gluteal and thigh regions, affecting an estimated 80-98% of postpubertal women. Innovative treatments for cellulite dimpling in the buttocks have gained popularity in recent years, seeking new solutions for a historically challenging condition. In this open-label, investigator-initiated, single-center, prospective clinical study, the authors sought to evaluate the safety and efficacy of diluted calcium hydroxylapatite (CaHA; Radiesse®, Merz Aesthetics, Raleigh, NC) for the treatment of cellulite dimpling in the buttocks of adult women. METHODS: Subjects underwent three treatment sessions, receiving a total of 12 syringes of 1:1 diluted CaHA administered using a cannula-based subcision technique. Endpoints included the cellulite severity scale (CSS), the global aesthetic improvement scale (GAIS), subject satisfaction measured on a 5-point scale, and three-dimensional imaging analysis via the Quantificare 3D Track®. RESULTS: Twenty-four subjects completed the study (mean age, 35 years; mean BMI, 26.88 kg/m2; mean body fat percentage, 31.29%), and no serious complications were reported. Quantitative analysis at week 14 revealed a mean reduction of 54.0% in the number of visible dimples and 50.09% in dimple depth compared to baseline. The mean CSS score decreased by 4.29 points, representing a 43.92% improvement in cellulite severity from baseline (p < 0.0001). Both physician-assessed and subject-assessed GAIS ratings also demonstrated significant improvement, with 91.6% of subjects rating their cellulite appearance as "improved" or greater. CONCLUSION: The results of this study support the safety and efficacy of diluted CaHA for treating cellulite dimpling in adult women. LEVEL OF EVIDENCE II: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors   www.springer.com/00266 . CLINICAL TRIALS REGISTRATION: This study is registered with clinicaltrials.gov (ID: NCT05885035) and can be found at this link: https://clinicaltrials.gov/study/NCT05885035 .

Vaginal Bipolar Radiofrequency Treatment of Mild SUI: A Pilot Retrospective Study.

Background and Objectives: This retrospective study investigates the action of a bipolar, temperature controlled, endovaginal RF handpiece for the treatment of mild, moderate, and severe stress urinary incontinence with a minimally invasive approach. Stress urinary incontinence (SUI) is a common condition resulting in involuntary urine leakage, with an associated social and psychological impact. SUI is the most common type of urinary incontinence in women. Materials and Methods: We retrospectively studied 54 patients for this study. The bipolar radiofrequency energy used in all patients was 50 W, with temperatures maintained between 41 °C and 44 °C. Two sessions were performed four weeks apart. In order to monitor all patients before the first treatment and 4 months after the second treatment, the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) was used. Paired Student's t test was used to elaborate the statistical data. Results: The average frequency of urine leak improved from "2-3 times a week" (2.1 ± 1.3 points before the treatment) to "once a week" (0.8 ± 1.3 points 4 MFU post-treatment). The average volume improved from "small/moderate quantity" (3.2 ± 1.6 points before the treatment) to "none" (0.9 ± 1.4 points 4 MFU post-treatment). No adverse events or side effects were found. Conclusion: Our preliminary results represent a good starting point to check the effectiveness and validity of the bipolar radiofrequency temperature-controlled method in the treatment of SUI.

Device-Induced Neocollagenesis: Profibrotic Response or True Neocollagenesis?

BACKGROUND AND OBJECTIVES: Many light and radiofrequency-based rejuvenation devices have claimed to increase collagen production in the skin dermal tissue. However, there has not been enough scientific evidence to prove whether the result is just a profibrotic response or not. We aimed to find the optimal skin rejuvenation device that shows true neocollagenesis. STUDY DESIGN/MATERIALS AND METHODS: We evaluated dermal collagen thickness and gene expression of procollagen type 1, 3, matrix metalloproteinase-3 (MMP-3), and transforming growth factor-ß (TGF-ß) resulting from different energy-based devices in a rat model in vivo. The wound-healing response was evaluated histologically and by real-time polymerase chain reaction (RT-PCR) at immediate, 1st, 2nd, 4th, 8th, and 12th week after the initial procedure. RESULTS: At the 12th week, the most relevant changes of the dermal thickness were found in specimens after treatment with electrosurgical unit, fractional CO2 and 1064 nm Q-switched Nd:YAG. Procollagen 1 and 3 were also found to be the highest in electrosurgical unit, fractional CO2 , and microneedle radiofrequency. Dramatic changes of MMP-3 and TGF-ß were remarkable at the early observation but went back to normal level at 12th week. The ratio of procollagen 1 and 3 was found to be the lowest with Q-Switched Nd:YAG 1064 nm and fractional CO2 . CONCLUSION: Electrosurgical unit resulted in most significant changes, but due to irreversible thermal damage and extremely high procollagen results it is considered as a profibrotic response. Fractional CO2 and Q-Switched Nd:YAG 1064 nm are applicable to face skin rejuvenation treatment considering thickening of dermal tissue and lower procollagen 1:3 ratio similar to the neocollagenesis purpose. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.

Radiofrequency treatment induces fibroblast growth factor 2 expression and subsequently promotes neocollagenesis and neoangiogenesis in the skin tissue.

Radiofrequency (RF) treatment appears to be involved in production of new collagen fibrils and the improvement of existing collagen structures; however, the molecular bases of the effect of non-invasive RF on the skin tissue have not been fully elucidated. This study reports the effects of RF associated or not with hydrolyzed collagen (HC) in the skin tissue. Wistar rats were randomly divided into four groups, according to the treatment received: control group (G1, n = 5), no treatment; subjects in group G2 (n = 5) were treated with HC; and capacitive RF was applied to the back of each subject in G3 (n = 5) and RF associated with HC in G4 (n = 5). Biopsies were taken 30 days after treatment and then were histologically processed and studied for inflammatory cell counting, collagen content, and morphometry. In addition, FGF2, CD105, and COX-2 expression was assessed by immunohistochemical staining. The most relevant changes were the increase in cellularity and accumulation of intercellular substance in RF-treated animals (G3 and G4). The greatest dermis thickness rate was observed in G4, followed by G3 and G2 (p < 0.05). RF-treated skins (G3 and G4) exhibited a significant overexpression of FGF2 (p < 0.0001) and increased microvessel density (p < 0.0001) in comparison with G1 and G2. Moreover, the amount of COX-2 was significantly higher (p < 0.0001) in dermis of RF-treated areas compared to G1 and G2, and demonstrated differences in G3 (RF) compared to G4 (RF + HC) (p < 0.0001). Our results suggests that RF treatment associated or not with HC induces FGF2 overexpression, promotes neoangiogenesis and modulates the COX-2 expression, subsequently promotes neocollagenesis, and increased thickness rate of dermis.

Neocollagenesis in human tissue injected with a polycaprolactone-based dermal filler.

A novel dermal filler containing polycaprolactone (PCL) has been introduced into the aesthetic market. A recently published study has shown that the PCL-based dermal filler induces neocollagenesis, a process associated with improvement in appearance of the skin, in rabbit tissue. In this pilot study, we investigated whether the PCL-based dermal filler induces neocollagenesis in human tissue by histological analysis. Two patients who were enrolled in the study, and were willing to undergo temple lifting surgery, were injected intra-dermally with the PCL-based dermal filler. Thirteen months post-injection, biopsies were obtained for subsequent histological analysis. Histological analysis of tissue obtained from the biopsies (13 months post-injection) revealed that the PCL-based dermal filler shows collagen formation around the PCL particles and, therefore, supports similar findings previously shown in rabbit tissue. In conclusion, PCL particles are maintained in their original state 13 months post-injection.

Comparative histometric analysis of the effects of high-intensity focused ultrasound and radiofrequency on skin.

INTRODUCTION: High-intensity focused ultrasound (HIFU) and radiofrequency (RF) are used for non-invasive skin tightening. Neocollagenesis and neoelastogenesis have been reported to have a mechanism of controlled thermal injury. OBJECTIVE: To compare neocollagenesis and neoelastogenesis in each layer of the dermis after each session of HIFU and monopolar RF. METHODS: We analyzed the area fraction of collagen and elastic fibers using the Masson's Trichrome and Victoria blue special stains, respectively, before and after 2 months of treatments. Histometric analyses were performed in each layer of the dermis, including the papillary dermis, and upper, mid, and deep reticular dermis. RESULTS: Monopolar RF led to neocollagenesis in the papillary dermis, and upper, mid, and deep reticular dermis, and neoelastogenesis in the papillary dermis, and upper and mid reticular dermis. HIFU led to neocollagenesis in the mid and deep reticular dermis and neoelastogenesis in the deep reticular dermis. Among these treatment methods, HIFU showed the highest level of neocollagenesis and neoelastogenesis in the deep reticular dermis. CONCLUSIONS: HIFU affects deep tissues and impacts focal regions. Monopolar RF also affects deep tissues, but impacts diffuse regions. We believe these data provide further insight into effective skin tightening.

Monopolar radiofrequency for dermal temperature regulation and remodeling: A porcine model study.

BACKGROUND: Noninvasive monopolar radiofrequency (NMRF) is widely used for dermal and subdermal volumetric heating, yet detailed research on its effects on dermal temperature is scarce. AIMS: This study evaluates the impact of NMRF on dermal temperature and its potential for dermal remodeling using a porcine model. METHODS: Noninvasive monopolar radiofrequency was applied to porcine skin with temperature monitoring via optic fiber technology and forward-looking infrared thermal imaging. Safety was evaluated using nitro blue tetrazolium chloride assessments, and effectiveness was determined through histological examinations before and after treatment. RESULTS: Noninvasive monopolar radiofrequency treatment in a porcine model achieved effective dermal remodeling with no thermal damage, recording peak temperatures of 50°C, 60°C, and 70°C. Histological analysis showed increased collagen density, indicating successful tissue remodeling. CONCLUSION: Noninvasive monopolar radiofrequency is effective in delivering controlled dermal heating and enhancing collagen synthesis, promoting safe and efficient skin tightening and dermal remodeling in a porcine model. It presents a viable option for skin rejuvenation therapies.

New Regenerative and Anti-Aging Medicine Approach Based on Single-Stranded Alpha-1 Collagen for Neo-Collagenesis Induction: Clinical and Instrumental Experience of a New Injective Polycomponent Formulation for Dermal Regeneration.

This study explores the efficacy of a novel polycomponent formulation (KARISMA Rh Collagen® FACE, Taumedika Srl, Rome, Italy), containing 200 mg/mL of non-crosslinked high-molecular-weight hyaluronic acid (HMW-HA), 200 µg/mL of a human recombinant polypeptide of collagen-1 alpha chain, and 40 mg/mL of carboxymethyl cellulose (CMC) as a regenerative medicine for skin regeneration and rejuvenation. This formulation combines non-crosslinked high-molecular-weight hyaluronic acid, human recombinant polypeptide of collagen-1 alpha chain, and carboxymethyl cellulose to stimulate collagen type I production and enhance skin hydration. This study involved 100 subjects with varying skin conditions, divided into three groups based on skin aging, smoking history, and facial scarring, to evaluate the product's effectiveness in skin regeneration and aesthetic improvement. The methodology included two injections of Karisma (2 mL for each injection) one month apart, with evaluations conducted using FACE-Q questionnaires, the SGAIS Questionnaire, and Antera 3D skin scanner measurements at baseline, 30 days, and 60 days post-treatment. The results demonstrated a significant reduction in skin roughness and an improvement in skin quality across all the groups, with no correlation between the outcomes and the patient's age. The subjective assessments also indicated high satisfaction with the treatment's aesthetic results. The analyzed data allow us to conclude that the single-stranded collagen with hyaluronic acid and carboxymethyl-cellulose formulation is able to stimulate the skin's regenerative response, yielding significant results both in vitro and, through our study, also in vivo. This new polycomponent formulation effectively stimulates skin regeneration, improving skin quality and texture, with significant aesthetic benefits perceived by patients, and a low incidence of adverse events, marking a promising advancement in regenerative medicine.

Buttocks Beautification 3D with Calcium Hydroxylapatite (RadiesseTM): An Individualized Approach to Diagnosing and Treating Contour, Sagging, and Cellulite of the Buttocks in Seven Cases.

Background: The demand for body procedures is increasing, and buttocks beautification is one of the most sought-after procedures in dermatological and plastic surgery clinics. Several aspects affect the beauty of this area, including sagging, cellulite, contour irregularity, and volume reduction. This makes treatment of the area more challenging. Calcium hydroxylapatite (CaHA), which may be injected into the buttocks, stimulates local neocollagenesis, provides volume replacement, increases the strength and elasticity of the dermis, and thickens the underlying superficial fascia. However, no protocol for buttocks beautification tailors the dilution and deep application of CaHA filler simultaneously according to clinical assessments and personal priorities regarding contour, sagging, and cellulite. Purpose: To report the results of a minimally invasive protocol using different dilutions of CaHA (Buttocks Beautification 3D) in the buttocks with application in different planes. The treatment was performed according to a previous individualized evaluation to improve the area aesthetically. Patients and methods: Six women and one man were submitted to the protocol. An assessment was performed to determine the shape, sagging, cellulite (in women), and patients' preferences for buttocks beautification. The dilution, volume, depth, and injection technique for CaHA were based on these assessments. The results of the treatment were then assessed using standardized photographs and patient satisfaction. Results: We reported favorable results in six women and one man with different grades of sagging, female cellulite, and shapes of the gluteal region who were treated with CaHA injections according to a tailored protocol. All participants reported high satisfaction with the procedure. Conclusion: Highly satisfactory results were achieved in seven adult patients who were assessed and treated for the buttocks with CaHA using an individualized protocol. Prospective studies should be performed to corroborate our findings and optimize the use of Buttocks Beautification 3D as a reliable modality of treatment for this body area.

Histological effects of a combined collagen stimulation procedure consisting of microfocused ultrasound, soft tissue filler, and Ca-HA injections.

BACKGROUND: An increasing demand for in-office aesthetic procedures aiming to improve collagen stimulation has been reported. OBJECTIVE: To analyze the effects of combinations of different aesthetic collagen stimulation procedures using histological analysis. METHODS: Histological analysis was performed on skin samples of the excess skin of a 60-year-old patient after sub-superficial musculo-aponeurotic system facelift surgery. The excess skin before facelift surgery was divided into three areas per hemiface. Each area-with exception of area A as a control-received an isolated or combined treatment of microfocused ultrasound (MFU), injections of calcium-hydroxylapatite/hyaluronic-acid-based soft tissue filler, and microneedling. The effect of the treatments was analyzed using histological analysis with H&E coloration and PAS staining. RESULTS: A threefold increase of epidermal and dermal thickness was achieved by treating the skin with the proposed combined treatment comprising MFU and injections of calcium-hydroxylapatite- and hyaluronic-acid-based soft tissue fillers. CONCLUSION: The investigated treatments act synergistically in the production of collagen and combining these treatments allows for an increase in collagen production.

Efficacy and Tolerability of Hyperdiluted Calcium Hydroxylapatite (Radiesse) for Neck Rejuvenation: Clinical and Ultrasonographic Assessment.

Background: The subdermal injection of calcium hydroxylapatite (CaHA) can improve the mechanical properties of the skin, providing immediate correction and stimulating the endogenous production of collagen, elastin, angiogenesis, and dermal cell proliferation; however, few studies have examined the neck region. Purpose: This study assessed the clinical and ultrasonographic improvement induced by two sessions of subdermal injection of hyperdiluted (1:4) CaHA for neck rejuvenation in 22 women. Patients and Methods: A quasi-experimental longitudinal trial (before and after) was performed by enrolling 22 adult women with mild and moderate neck aging (grades 1 and 2) on Merz Neck Volume Scale at rest (laxity) and Neck Horizontal Lines. They were submitted to two sessions of subdermal hyperdiluted CaHA (D0 and D45) treatments and assessed clinically and ultrasonographically at D0, D45, and D120. The main outcomes were the blinded photographic assessment (Merz scales of neck laxity and horizontal lines), dermal thickness (at three points), and the GAIS (Global Aesthetic Improvement Scale) score. Results: The mean (SD) age was 43.5 (5.6) years. At the inclusion, the Merz scores for neck laxity were mild for 27% and moderate for 73% of participants, and the Merz scores for necklines were mild for 32% and moderate for 68%. At D120, scores decreased in 86% (95% CI 68-99%) of the participants by at least one degree on the necklines scale and in 82% (95% CI 73-90%) for neck laxity. According to the GAIS, 91% (95% CI 77-99%) of the participants evidenced improvement at D120. The mean dermal thickness increased by 15% (95% CI 8-21%) at D120. No severe adverse effects were recorded, and high satisfaction was reported by 82% of the participants. Conclusion: Two sessions of subdermal hyperdiluted CaHA were well-tolerated and improved necklines, neck laxity, and dermal thickness in adult women with mild and moderate cervical aging.

Minimally Invasive Techniques for Facial Rejuvenation Utilizing Polydioxanone Threads.

Cosmetic procedures to combat the effects of aging are increasing in demand. Surgical interventions, such as rhytidectomy, have long been the standard method of providing a more youthful appearance. However, these procedures are costly, often require general anesthesia, and have potential risks such as scarring and prolonged recovery. A safe, effective, alternative to surgery is the nonsurgical thread-lift. Nevertheless, proper patient selection is critical for optimal outcomes and for patient and provider satisfaction. Over the past decade, these treatments have gained significant popularity for patients to achieve a more rejuvenated appearance with less complications and minimal downtime.

Sustained Release Microneedles: Materials and Applications in Facial Rejuvenation.

Wrinkled and loose skin resulting from collagen degradation along with fibers decreasing reflects the youth diminishing. Microneedles (MNs) have opened up new avenues for the development of painless and noninvasive transdermal drug delivery systems for facial rejuvenation. Encapsulated drugs or molecules are transmitted to targeted tissues via percutaneous microchannels, which eliminate potential gastric stimulation or first-pass metabolic effects, as well as boost patient compliance. Although MNs are considered effective and feasible therapeutic alternatives to metals, silicon, and polymers, traditional procedures with reduction processes continue to encounter methodological limitations. In recent years, promising additive manufacturing processes such as three-dimensional printing and two-photon polymerization manufacturing have been developed with the aim of overcoming the limitations by traditional processes to facilitate an efficient and economic production mode. This review summarizes the design, material selection, and manufacturing method for recently advanced MN systems. Furthermore, we also highlight specific polymeric or natural microneedle products, like hyaluronan, plant derivates, and vitamins, for esthetic applications in this review. Impact Statement In this review, the materials and manufactural routes of microneedles (MNs) are detailed. Moreover, similar to the diagnostic or therapeutic MNs, the feature of dispensation with training and ready-to-use is perfect for beautification and anti-aging, which necessitate repeated and long-term usage. Furthermore, the specific polymeric or natural products for esthetic applications of MNs are highlighted in this review.

Contouring Plus: A Comprehensive Approach of the Lower Third of the Face with Calcium Hydroxylapatite and Hyaluronic Acid.

A well-defined jawline is aesthetically pleasing, so that rejuvenation of the jawline is becoming part of routine aesthetic practice. Restoring balance to the lower face without surgical intervention requires a multiple treatment approach, among which the minimally invasive injectables play a central role. Nevertheless, amidst the plethora of different injectable products available, choosing the option that best suits the patient's need can be a challenge. A panel of experts sought to describe herein 4 clinical cases, illustrating the Contouring Plus technique, which provides a practical guidance for lower third assessment, choice of products, and treatment execution, especially among hyaluronic acid and calcium hydroxylapatite, aiming for immediate, as well as mid-to-long-term results.

Laser emission at 675 nm: In vitro study evidence of a promising role in skin rejuvenation.

Light-based therapies have been proven to influence and perhaps reverse skin ageing at clinical, molecular and histologic levels. Laser technology decreases photodamage by promoting collagen type I and III synthesis and enhancing the expression of heat shock protein. Aims: This study aims to assess different doses of 675 nm irradiation on human dermal fibroblast cells to evaluate the potential therapeutic effects on the rejuvenation process. Methods: This study employed a laser system that emits 675 nm wavelength: 260, 390, 520 and 650 J/cm2 doses were tested on adult human dermal fibroblast cells. Cellular viability, proliferation, and synthesis of type I and III collagen were studied. Results: No dose tested showed effects on cell viability and proliferation at 24 and 48 h from the irradiation. Doses of 260 and 520 J/cm2 causes a significant decrease in type I collagen fluorescence intensity, while 390 J/cm2 elicits a significant increase in type III collagen expression. Conclusions: Our results showed that 675 nm laser irradiation does not affect cell viability while modulating cell proliferation and collagen synthesis in human adult cultured fibroblasts in vitro. These findings suggest that 675 nm laser irradiation potentially plays a role in skin rejuvenation.

Comparison of the efficacies of polycaprolactone filler and lidocaine-added filler on neocollagenesis in a rat model.

BACKGROUND: Polycaprolactone (PCL) is a semi-permanent filler stimulating neocollagenesis. Lidocaine is frequently used to reduce the pain and, however, may have negative effects on collagen. It was aimed to compare the histological changes on rat skin and efficacies of PCL filler and lidocaine addition. OBJECTIVE: In this study, results of PCL and PCL+Lidocaine application on rat skin were compared using hematoxylin-eosin (H&E) staining, Masson's trichrome (MT) staining, and electron microscope (EM). METHODS: A total of 30 adult female rats were divided into three groups: the control group, the PCL group, and the PCL+Lidocaine group. The tissue samples taken at months 2 and 4 were examined using H&E, MT, and EM. RESULTS: At month 2, dermis thickness, fibroblast count, and collagen fiber diameter increased similarly in the PCL and PCL+Lidocaine groups. Collagen fiber diameter was significantly higher in the PCL group than in the PCL+Lidocaine (p:0.016) and control groups (p:0.009). At month 4, no significant difference was detected between the PCL and PCL+Lidocaine groups in terms of fibroblast count, collagen fiber count, and collagen fiber diameter; dermis thickness was lower in the PCL+Lidocaine group at month 4 (p < 0.46). Dermis thickness, fibroblast count, collagen fiber count, and collagen fiber diameter were found to be significantly lower than in the PCL and PCL+Lidocaine groups. CONCLUSIONS: Our study showed that lidocaine addition to PCL filler does not affect the efficacy of the filler and PCL filler stimulates neocollagenesis.