Hyaluronic Acid: Production Strategies, Gel-Forming Properties, and Advances in Drug Delivery Systems

Abstract

Hyaluronic acid (HA) is a naturally occurring glycosaminoglycan widely recognised for its biocompatibility, biodegradability, and unique viscoelastic properties. Its structural versatility enables the formation of hydrogels with tuneable physicochemical characteristics, making it a valuable biomaterial in drug delivery and regenerative medicine. This review outlines HA properties, gel-forming approaches, and modern medicine and bioengineering applications. It provides a comprehensive overview of advances in HA production strategies, including microbial fermentation, animal tissue extraction, and production in vitro. Particular attention is given to gel-forming mechanisms, emphasising physical and chemical crosslinking methods like carbodiimide crosslinking, radical polymerisation, and enzymatic crosslinking. Advances in HA-based drug delivery systems and applications of HA-based materials in tissue engineering are also discussed, focusing on HA-based hydrogels with conjugates and combinations with compounds like collagen, alginate, and chitosan.