Research Article: Hyaluronan-based hydrogels as dermal fillers: The biophysical properties that translate into a “volumetric” effect

Date Published: June 11, 2019

Publisher: Public Library of Science

Author(s): Annalisa La Gatta, Rosanna Salzillo, Claudia Catalano, Antonella D’Agostino, Anna Virginia Adriana Pirozzi, Mario De Rosa, Chiara Schiraldi, Bing Xu.

http://doi.org/10.1371/journal.pone.0218287

Abstract

Biophysical and biochemical data on hyaluronan (HA)-based dermal fillers strongly support their optimal use and design to meet specific requisites. Here, four commercially available (in Europe) HA “volumetric” fillers, among the most used in the clinical practice, have been characterized in vitro. Analyses revealed the highest amounts of water-soluble HA reported so far and provided hydrodynamic data for these soluble polymeric fractions. Volumetric gels exhibit a wide range of rigidity with most of them showing G’ values around 200-300Pa. They greatly differ in cohesivity. 1mL of gel hydrates up to 2.4–3.2mL. The products completely solubilize due to Bovine Testicular Hyaluronidase (BTH)’s action, thus predicting in vivo complete resorption. For the first time, filler degradation due to reactive oxygen species (ROS) was studied by rheological measurements and a rank in stability was established. Studies using Human Dermal Fibroblasts (HDF) indicated a positive biological response to the HA networks. Further, gel capacity to prompt collagen I, elastin and aquaporin3 synthesis was demonstrated, thus suggesting a positive effect on skin elasticity and hydration, besides the physical volumetric action. The findings are the first wide assessment of features for the volumetric class of HA-fillers and include first data on their resistance to degradation by ROS and biological effects on HDF. The study represents a valuable contribution to the understanding of HA-fillers, useful to optimize their use and manufacture.

Partial Text

Hyaluronan (HA)-based hydrogels, obtained by crosslinking the biopolymer with 1,4 butandiolediglycidylether (BDDE), are the most commonly used dermal fillers in aesthetic medicine procedures for facial rejuvenation [1–4]. Diverse proprietary manufacturing technologies (i.e., Vycross, NASHA, CMP etc.) have been developed and are currently employed for HA filler production [3,5,6]. As the understanding of processes governing facial aging improves, HA gel design is being upgraded to match specific clinical needs. As a consequence, each brand markets a line of formulations, possibly based on the same technology but tuned to address the diverse needs for a full face restoration.

To provide biophysical and biochemical parameters describing HA hydrogels clinically used as volumetric dermal fillers, an extensive in vitro characterization of four commercial gels was carried out. New methods to evaluate this kind of hydrogels were also presented.

A broad in vitro characterization of HA-based dermal fillers with the same indications as volumetric gels was accomplished. Data allowed us to establish a range of rheological properties, hydration capacity, HA soluble fraction extent and cohesivity that well characterize these products. Differences in behavior among the fillers were also highlighted. Further, degradation due to ROS was systematically monitored exploiting rheological measurements proving diverse sensitivity of the gels tested. Finally, the boost in elastin, collagen and Aqp3 production for HDF cultured in the presence of the fillers was demonstrated thus supporting the lately emerged opinion of a biological positive effect of HA dermal fillers on skin restoration and hydration.

 

Source:

http://doi.org/10.1371/journal.pone.0218287

 

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