In Vitro Evaluation of the Biological Availability of Hyaluronic Acid Polyethylene Glycols-Cross-Linked Hydrogels to Bovine Testes Hyaluronidase.

During last years, hyaluronic acid- (HA-) based dermal fillers have grown rapidly and continuously, as reported by the American Society of Aesthetic Plastic Surgery (ASAPS). In fact, HA fillers are considered the gold standard technique for soft tissue augmentation, deep skin hydration, and facial recontouring, playing a key role as an alternative to plastic surgery. HA fillers are less invasive, more biocompatible, and safer and with a more natural and immediate result if compared to plastic surgery. Hence, the safety of HA-based dermal fillers plays a crucial role, mostly in terms of biocompatibility and adjustability in case of unpleasant results and side effects such as, tyndall effect, edema, or granulomas. Hyaluronidase is a naturally occurring enzyme, present in the human body, and can degrade HA fillers avoiding more severe complications. In this article, we analyzed the bioavailability of hyaluronidase degradation of five fillers of Neauvia® hydrogels line (MatexLab SA, Lugano, CH), composed of pure hyaluronic acid and based on PEGDE cross-linking (polyethylene glycol) technology that guarantees a higher biocompatibility and an optimal biointegration and rheological characteristics. The performed in vitro testing is based on the colorimetric determination of the N-acetyl-D-glucosamine (NAG) present in solution after incubation with hyaluronidase, determined at different time points in order to assess the kinetic of each product degradation (1h, 3h, 6h, 24h, 48h, 72h, 120h, and 168h). The aim of this study was to assess, in vitro, how the difference in HA content and PEGDE concentration of the analyzed fillers can influence the product biocompatibility, intended as product enzymatic clearance and duration in time. The results demonstrated that the method was reproducible and easy to perform and that all the analyzed fillers are naturally immediately available for hyaluronidase-mediated degradation.

In vitro evaluation of collagen production on human fibroblasts treated with hyaluronic acid peg cross-linked with micromolecules of calcium hydroxyapatite in low concentration.

Neauvia Stimulate® is a biocompatible, injectable hyaluronic acid (HA) filler (26 mg/ml) PEG cross-linked with 1% of calcium hydroxyapatite (CaHA) for facial soft-tissue augmentation that provides volume to tissues, followed by a process of neocollagenesis for improving skin quality. The aim of the present study is to evaluate the possible modulation of collagen synthesis after treating human fibroblasts cultured in vitro with the product (Lot. 160517-26-1/2 PEG). The experimental model proposed, despite being an in vitro system, allows the derivation of useful information to predict the possible activity of the product in further in vivo application. Human fibroblasts (PEU cells) were treated with the product for 24 h at increasing concentrations of compared to control (untreated cells). The modulation of collagen synthesis was evaluated using a specific colorimetric kit (Sircol, Soluble Collagen Assay Kit). Increment of collagen production, 37.62% and 97.39% at concentrations of 1.25 mg/ml and 2.5 mg/ml of product, respectively, was considered to be statistically significant (*p values≤0.05 and **p values≤0.01) when compared with control (untreated cells). In conclusion, Hyaluronic Acid Hydrogel 26 mg/ml PEG cross-linked with calcium hydroxyapatite in low concentrations (1%) determines a statistical increment in neocollagenesis.