Investigation of Crosslinking Parameters and Characterization of Hyaluronic Acid Dermal Fillers: From Design to Product Performances

Abstract

Despite process similarities, distinctive manufacturing technologies offer hyaluronic acid dermal fillers with different in vitro physicochemical and rheological properties due to peculiar crosslinked hydrogel networks. A better understanding of dermal filler properties could provide specific clinical indications and expectations with more accurate performance correlations. In this study, with an emphasis on the degree of modification, hyaluronic acid concentration and molecular weight, these process parameters were able to modulate dermal filler properties, especially rheology. Moreover, an extensive characterization of commercial hyaluronic acid injectables of the Hyal System line was described to present product properties and help to elucidate related clinical effects. Standardized methodologies were applied to correlate in vitro parameters with feasible clinical indications. In view of an optimized dermal filler design, the results of the extrudability measurements allowed the quantification of the effect of hydrogel composition, rheological properties and needle size on injectability. Composition, dynamic viscosity and needle size showed an impactful influence on hydrogel extrudability. Finally, the positive influence of 200 KDa hyaluronic acid in comparison to fragments of ether-crosslinked hyaluronic acid on fibroblast recognition were shown with a migration assay.

Dual Functionalization of Hyaluronan Dermal Fillers with Vitamin B3: Efficient Combination of Bio-Stimulation Properties with Hydrogel System Resilience Enhancement

“…Furthermore, there are various cross-linking degree measurement methods (e.g., size-exclusion chromatography with mass spectrometry [SEC-MS] or nuclear magnetic resonance [NMR]), wherein a lack of methodological homogeneity exists. Currently, there is no consensus on the optimal method to use in order to determine these parameters [ 12 , 55 , 56 ].…”

“…Therein, most commercial HA-based products are indicated for facial volume loss due to age-related bone and fat resorption. Importantly, such devices are often obtained via HA chemical cross-linking with 1,4-butanediol diglycidylether (BDDE), as described in various manufacturing technologies (e.g., VYCROSS ® , CPM ® , Preserved Network ® , IPN-Like ® , or OxiFree™) [ 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 ]. The numerous variants for chemical modifications of HA, exploited in order to obtain physico-chemical advantages, are well-described in the literature [ 14 ].…”

Current Knowledge and Regulatory Framework on the Use of Hyaluronic Acid for Aesthetic Injectable Skin Rejuvenation Treatments

“…The modifications of the hydroxyl groups can come from four different reaction types: oxidation, ester formation, ether formation, or hemiacetal formation. Some of the reagents used in these reactions are 1,4-butanediol-diglycidyl ether (BDDE), poly(ethylene glycol) diglycidyl ether (PEGDE), and divinyl sulfone (DVS) [85][86][87][88][89][90]. BDDE and PEGDE are the most common crosslinking agents for the manufacture of hyaluronic acid dermal fillers.…”

Comprehensive Evaluation of Injectability Attributes in OxiFree™ Dermal Fillers: MaiLi® Product Variants and Clinical Case Reports

“…Importantly, hydrogel product injectability attributes may be studied in diverse experimental setups and are often leveraged by manufacturers as technical features (i.e., to optimize clinician and patient experience of care) [27][28][29][30]. Notwithstanding, tangible correlations may be made between the quality level of dermal filler product injectability and the safety or efficacy outcomes of the treatment [1].…”