Preparation and Rheological Evaluation of Thiol–Maleimide/Thiol–Thiol Double Self-Crosslinking Hyaluronic Acid-Based Hydrogels as Dermal Fillers for Aesthetic Medicine

This study presents the development of thiol-maleimide/thiol-thiol double self-crosslinking hyaluronic acid-based (<i>dsc</i>HA) hydrogels for use as dermal fillers. Hyaluronic acid with varying degrees of maleimide substitution (10%, 20%, and 30%) was synthesized and characterized, and <i>dsc</i>HA hydrogels were fabricated using two molecular weights of four-arm polyethylene glycol (PEG10K/20K)-thiol as crosslinkers. The six resulting <i>dsc</i>HA hydrogels demonstrated solid-like behavior with distinct physical and rheological properties. SEM analysis revealed a decrease in porosity with higher crosslinker MW and maleimide substitution. The swelling ratios of the six hydrogels reached equilibrium at approximately 1 h and ranged from 20% to 35%, indicating relatively low swelling. Degradation rates decreased with increasing maleimide substitution, while crosslinker MW had little effect. Higher maleimide substitution also required greater injection force. Elastic modulus (G') in the linear viscoelastic region increased with maleimide substitution and crosslinker MW, indicating enhanced firmness. All hydrogels displayed similar creep-recovery behavior, showing instantaneous deformation under constant stress. Alternate-step strain tests indicated that all six <i>dsc</i>HA hydrogels could maintain elasticity, allowing them to integrate with the surrounding tissue via viscous deformation caused by the stress exerted by changes in facial expression. Ultimately, the connection between the clinical performance of the obtained <i>dsc</i>HA hydrogels used as dermal filler and their physicochemical and rheological properties was discussed to aid clinicians in the selection of the most appropriate hydrogel for facial rejuvenation. While these findings are promising, further studies are required to assess irritation, toxicity, and in vivo degradation before clinical use. Overall, it was concluded that all six <i>dsc</i>HA hydrogels show promise as dermal fillers for various facial regions.