Injectable hyaluronic acid hydrogels via Michael addition as dermal fillers for skin regeneration applications.

This study presents the development of injectable hydrogels based on hyaluronic acid for dermal filler applications, synthesized via Michael-type addition reactions between thiolated hyaluronic acid and polyethylene glycol derivatives. By varying thiol substitution, crosslinking kinetics and hydrogel properties were optimized. Biphasic gel formulations comprising crosslinked hyaluronic acid microparticles in a non-reactive fluid phase matrix enhances injectability and versatility. Key properties, including enzymatic degradation, injectability, and rheology, were evaluated, alongside a three-dimensional culture model to simulate dermal remodelling. Selected gel formulations promoted balanced collagen synthesis and degradation, essential for skin regeneration, while showing a controlled inflammatory response, supporting tissue repair and reducing adverse effects. These findings position these hydrogels as promising candidates for safe and effective dermal filler, supporting tissue remodelling and inflammation management.