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

Abstract

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.

Chemical and mechanical characterization of hyaluronic acid hydrogel cross‐linked with polyethylen glycol and its use in dermatology

“…The hydrogel properties are dictated by the number of crosslinks, obtained by the reaction of HA and CL present. In the world of fillers, the preferred reaction between HA and CL leads to the formation of covalent bonds in order to increase the hydrogel resistance to the attacks of hyaluronidase, 16,17 and, as a result, to increase the postimplant duration in the dermis. Usually, the formation of ether bonds COC is sought, as they are stable in physiological conditions in the dermis.…”

“…The hydrogel properties are dictated by the number of crosslinks, obtained by the reaction of HA and CL present. In the world of fillers, the preferred reaction between HA and CL leads to the formation of covalent bonds in order to increase the hydrogel resistance to the attacks of hyaluronidase, 16,17 and, as a result, to increase the post- Polyethylene glycol (PEG) is a highly investigated polymer for the covalent modification of biological macromolecules and surfaces for many pharmaceutical and biotechnical applications. 5 PEG is a linear or branched polyether with a wide range of applications in the biomedical field.…”

Immune profile of hyaluronic acid hydrogel polyethylene glycol crosslinked: An in vitro evaluation in human polymorphonuclear leukocytes

“…Our results concerning the ability of N‐Gel to modulate human PMN functions, including migration, oxidative metabolism, and TNF alpha and IL‐8 expression, suggests that N‐Gel carries a very low risk of immune‐mediated adverse effects, particularly granulomatous reaction and associated cellulitic processes. In dermal cosmetics, as well as in aesthetic medicine, the use of products not only devoid of proinflammatory effects but also able to modulate any local inflammatory process, represents a significant opportunity, thus strengthening previous evidence and supporting N‐Gel as new frontier in dermal cosmetic 5,6,8‐10 …”

“…N‐Gel can be considered completely biocompatible and degradable hydrogel. The chemical properties and techniques used to obtain N‐Gel are reported in the literature 4,7,8,10,16 …”

“…N‐Gel is used as a dermal filler for the correction of congenital or acquired soft tissue deficits. Rheology, chemical property, biocompatibility, and bio‐integration of N‐Gel were previously assessed 4‐10 ; however, so far its effect on immunity and inflammation has never been examined.…”