Rheology of Polymethylmethacrylate-Collagen Gel Filler: Physiochemical Properties and Clinical Applications.

BACKGROUND: Soft tissue fillers are comprised of a range of materials with differing physiochemical and rheologic (ie, flow) properties. These properties can inform treatment selection for specific anatomic areas, planes of injection, and clinical applications. OBJECTIVES: The aim of this study was to characterize the rheologic properties of polymethylmethacrylate (PMMA)-collagen gel for comparison with other available fillers. METHODS: Commercially available PMMA-collagen gel, hyaluronic acid (HA), and calcium hydroxylapatite (CaHA) fillers were obtained from their respective manufacturers. Measures of complex viscosity (η*) and elastic modulus (G') for each filler were collected at 0.7 Hz in triplicate according to standard procedures on a rotational rheometer fitted with a 40-mm steel plate at 25°C on a Peltier plate (500-µm gap). RESULTS: The measured η* and G' values for HA and CaHA fillers were in agreement with previously published data. The difference in η* between CaHA (mean [standard deviation], 358.9 [21.56] Pa-s) and PMMA-collagen gel (656.41 [68.03] Pa-s) was statistically significant (P < 0.0001), as was the difference between the G' of CaHA (1424.8 [83.3] Pa) and the G' of PMMA-collagen gel (2815.27 [304.07] Pa; P < 0.0001). CONCLUSIONS: PMMA-collagen gel exhibited the highest η* and G' of all tested fillers. These properties likely underpin an increased capacity for lifting and support in areas where long-lasting revolumization is appropriate. In practice, PMMA-collagen gel is well suited for treatment of acne scars, as well as injection into the supraperiosteal plane in the temple, chin, mandible, and piriform by a retrograde linear threading technique. Additional clinical considerations are discussed.

Postmarket Experience of Polymethylmethacrylate-Collagen Gel Dermal Filler.

BACKGROUND: This report synthesizes 12 years of postmarket surveillance data (PMSD) for polymethylmethacrylate (PMMA)-collagen gel dermal filler. OBJECTIVE: To present PMMA-collagen gel PMSD findings on real-world safety. METHODS: Postmarket surveillance data were collected from January 2007 to December 2018 and evaluated to determine the overall adverse event (AE) complaint rate, the nature of reported AEs, and whether the complaint included on-label, off-label, both, or unknown areas. RESULTS: In the 12 years examined, 754,229 PMMA-collagen gel syringes were distributed worldwide, and 839 product-related complaints (including those classified as unknown) resulted in an overall complaint rate of 0.11%. The 3 most frequent primary complaints in AE reports were lump/bump (309/839, 37%), nodule (152/839, 18%), and swelling (138/839, 16%). Histologically confirmed granuloma accounted for 17/839 complaints (2.0%; overall complaint rate of 0.002%), and histologically unconfirmed granuloma accounted for 66/839 complaints (8%; overall rate of 0.009%). There were 666 complaints representing AEs related to off-label injection in which the periocular area was most frequently represented. CONCLUSION: Although a limiting factor across all PMSD is voluntary reporting and resultant underrepresentation of AEs, the PMSD reported here are consistent with safety findings from US clinical studies in more than 1,500 patients with up to 5 years of follow-up.

Histologic Characterization of Polymethylmethacrylate Dermal Filler Biostimulatory Properties in Human Skin.

BACKGROUND: Little literature exits on the mechanism of action of implanted polymethylmethacrylate (PMMA) filler. OBJECTIVE: To characterize PMMA-induced dermal extracellular matrix production in the skin. MATERIALS AND METHODS: Single-center, open-label prospective study in healthy volunteers undergoing removal of redundant skin was injected intradermally and subdermally with PMMA dermal filler (Bellafill). Punch biopsies were harvested over a time course and evaluated for the deposition of collagen-3 and procollagen-1, proteoglycans and elastin using immunohistochemistry. Blinded histopathologic readings were performed by a dermatopathologist to characterize the nature of the dermal extracellular matrix findings. RESULTS: Normal inflammatory infiltrate was exhibited at all timepoints after PMMA injection with an influx of fibroblasts and new vasculature. Tissue proteoglycans were noted within the injectate beginning at Week 1 and persisted through the study end point. Increased collagen Type 3 was evident following the first week after injection, peaked at Month 2 and diminished through Months 3 through 6. Procollagen-1 was noted at Month 1 and continued to increase in intensity and organization through the study end point (6 months). Elastin staining was inconclusive. Polymethylmethacrylate microspheres remained within the initial injection area and became encapsulated within new collagen fibers. The growth and pattern of new connective tissue mimicked a normal wound healing response. CONCLUSION: Polymethylmethacrylate-collagen gel filler stimulates collagen-3 and procollagen-1 when injected into human skin. This combination of neocollagenesis followed by microencapsulation of PMMA microspheres in the new tissue provides for long-lasting results.

Treatment of Atrophic Facial Acne Scars With Microneedling Followed by Polymethylmethacrylate-Collagen Gel Dermal Filler.

BACKGROUND: Microneedling and soft-tissue filler injections have been used independently to improve acne scarring. The effectiveness of a combined approach using microneedling followed by polymethylmethacrylate (PMMA)-collagen gel has not been carefully studied. OBJECTIVE: The goal of this study was to assess the effectiveness and safety of microneedling alone versus microneedling followed by injection of PMMA-collagen gel filler for correction of atrophic facial acne scars. METHODS: We conducted a multicenter, open-label, randomized, prospective study on subjects with distensible atrophic acne scars in the face to determine whether microneedling with PMMA-collagen gel is a superior acne scar treatment over microneedling alone. Forty-four subjects received 3 microneedling treatments over a 12-week period followed by randomization to treatments with PMMA-collagen gel (treatment group) or no further treatment (control group). RESULTS: At 24 weeks, the treatment group achieved a statistically significant improvement in acne scores over microneedling alone. The improvement continued at 36 weeks. At 24 weeks, the treatment group showed a strong trend in improvement on the Physician Global Aesthetic Improvement Scale compared with microneedling alone.

Evaluation of skin tissue effects from treatment with a novel hand-held plasma energy device.

INTRODUCTION: Plasma IQ™, the first FDA-cleared hand-held plasma energy device, is indicated for removal and destruction of skin lesions and coagulation of tissue. Treatment involves use of an electrostatic plasma spark to heat the skin and create discrete microthermal wounds. METHODS: Microthermal wounds on pre-auricular and upper eyelid skin from two individual subjects were created using multiple treatment parameters to assess the impacts of power, pulse duration and needle electrode type on wound depth, width and thermal spread, and analyzed using histology to characterize treatment effects. RESULTS: Device power had a statistically significant impact on upper eyelid skin microthermal wound depth and width (2-sided t-test p < 0.0001 for both) but not on thermal spread (p = 0.1171). No meaningful differences in wound width, depth, or thermal spread were observed based on pulse duration or electrode type. All microthermal wounds demonstrated dual zones of tissue injury and extended to the superficial reticular dermis. CONCLUSION: Treatment with the Plasma IQ™ device creates focal microthermal wounds of reproducible depth and width that are comprised of dual thermal injury zones similar to other plasma energy skin rejuvenation devices. Device power is the most important factor determining microthermal wound depth and width.

A self-sustaining endocytic-based loop promotes breast cancer plasticity leading to aggressiveness and pro-metastatic behavior.

The subversion of endocytic routes leads to malignant transformation and has been implicated in human cancers. However, there is scarce evidence for genetic alterations of endocytic proteins as causative in high incidence human cancers. Here, we report that Epsin 3 (EPN3) is an oncogene with prognostic and therapeutic relevance in breast cancer. Mechanistically, EPN3 drives breast tumorigenesis by increasing E-cadherin endocytosis, followed by the activation of a ß-catenin/TCF4-dependent partial epithelial-to-mesenchymal transition (EMT), followed by the establishment of a TGFß-dependent autocrine loop that sustains EMT. EPN3-induced partial EMT is instrumental for the transition from in situ to invasive breast carcinoma, and, accordingly, high EPN3 levels are detected at the invasive front of human breast cancers and independently predict metastatic rather than loco-regional recurrence. Thus, we uncover an endocytic-based mechanism able to generate TGFß-dependent regulatory loops conferring cellular plasticity and invasive behavior.

Cdc42 inhibits ERK-mediated collagenase-1 (MMP-1) expression in collagen-activated human keratinocytes.

Following injury, keratinocytes switch gene expression programs from the one that promotes differentiation to the one that supports migration. A common feature of human wounds and ulcerations of any form is the expression of matrix metalloproteinase 1 (MMP-1; collagenase-1) by leading-edge basal keratinocytes migrating across the dermal or provisional matrix. Induction of MMP-1 occurs by signaling from the α2ß1 integrin in contact with dermal fibrillar type I collagen, and the activity of MMP-1 is required for human keratinocytes to migrate on collagen. Thus, MMP-1 serves a critical role in the repair of damaged human skin. Here, we evaluated the mechanisms controlling MMP-1 expression in primary human keratinocytes from neonatal foreskin and adult female skin. Our results demonstrate that shortly following contact with type I collagen extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase were markedly activated, whereas c-Jun N-terminal kinase (JNK) phosphorylation remained at basal levels. ERK inhibition markedly blocked collagen-stimulated MMP-1 expression in keratinocytes. In contrast, inhibiting p38 or JNK pathways had no effect on MMP-1 production. Moreover, investigating the role of Rho GTPases revealed that Cdc42 attenuates MMP-1 expression by suppressing ERK activity. Thus, our data indicate that injured keratinocytes induce MMP-1 expression through ERK activation, and this process is negatively regulated by Cdc42 activity.