Hyaluronic acid chemistry and biomedical material design

Hyaluronic acid (HA) is a versatile biomaterial with broad application prospects in various medical fields, including tissue engineering, regenerative medicine, drug delivery, and medical devices. The continuous advancements of chemistry strategies and biomaterial design have been provided powerful tools for developing innovative HA-based materials and technologies. Through selective chemical modifications, diverse properties of HA, such as mechanical performance, biodegradability, processability, and interactions with biological systems, which can be enhanced or tailored to meet the requirements of distinct material formats (e.g., hydrogels, films, sponges, fibers) in medical applications. This review provides a comprehensive overview of the design and utility of HA-based biomaterials across different applications, with a particular emphasis on chemical strategies. The review is organized into three sections: (1) the fundamental properties and functionalization mechanisms of HA polysaccharides; (2) crosslinking chemistries enabling network formation, including composite biomaterials; (3) highlighted applications of HA in tissue engineering, drug delivery, 3D printing, microfluidics, and biosensors. Finally, we discuss design strategies for HA biomaterials to continuously enhance their clinical efficacy and application value.