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

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.

<p>Hyaluronan Dermal Fillers: Efforts Towards a Wider Biophysical Characterization and the Correlation of the Biophysical Parameters to the Clinical Outcome</p>

“…The stability of the gels to ROS action was studied using the H 2 O 2 /Cu 2+ system for generating radicals, as recently reported. 10 Briefly, aqueous solutions of H 2 O 2 and CuSO 4 were added to 1 mL of each gel to have H 2 O 2 375mM and CuSO 4 3.75mM (1.3 mL final volume). The suspensions were mixed and evaluated by rheological measurements.…”

“…Cohesivity was evaluated following a recent protocol reported by Sundaram and collaborators with slight modifications. [8][9][10] Specifically, 10 μL of Tb (0.1% w/w in PBS, pH7.4) were added to 1 g of each gel. 10 Staining was performed as indicated above.…”

“…In the field of aesthetic medicine, hyaluronic (HA)-based dermal fillers are among the most used products for the non-invasive treatment of skin defects. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16] Characterization studies of the commercial gels are intensifying since strongly aiding clinicians in the optimal use of available products also contributing to the Correspondence: Chiara Schiraldi via De Crecchio 7, Naples 80138, Italy Tel +39 081 5667546 Fax +39 081 5665897 Email chiara.schiraldi@unicampania.it establishment of the correlation between the biophysical parameters of a gel and the clinical outcome.…”

“…Other studies have focused on "cohesivity". [8][9][10] This is intended as the capacity of a filler to maintain its integrity without dissociating. This property is thought to correlate with a more uniform distribution in tissues, probably reducing the risk of lumps' formation and allowing a very superficial use without Tyndall effect.…”

“…To predict relative in vivo permanence of HA gels, many in vitro studies have been performed on HA filler stability to enzymatic action while stability to ROS has been poorly investigated up to now. 6,[10][11][12][13] The current trend in HA-filler use aims to a "naturallooking" full face remodeling thanks to the availability of diverse formulations designed for specific needs, including Aliaxin gels.…”