Hyaluronic acid-based multifunctional carriers for applications in regenerative medicine: A review

Hyaluronic acid (HA) is an important type of naturally derived carbohydrate polymer with specific polysaccharide macromolecular structures and multifaceted biological functions, including biocompatibility, low immunogenicity, biodegradability, and bioactivity. Specifically, HA hydrogels in a microscopic scale have been widely used for biomedical applications, such as drug delivery, tissue engineering, and medical cosmetology, considering their superior properties outperforming the more conventional monolithic hydrogels in network homogeneity, degradation profile, permeability, and injectability. Herein, we reviewed the recent progress in the preparation and applications of HA microgels in biomedical fields. We first summarized the fabrication of HA microgels by focusing on the different crosslinking/polymerization schemes for HA gelation and the miniaturized fabrication techniques for producing HA-based microparticles. We then highlighted the use of HA-based microgels for different applications in regenerative medicine, including cartilage repair, bioactive delivery, diagnostic imaging, modular tissue engineering. Finally, we discussed the challenges and future perspectives in bridging the translational gap in the utilization of HA-based microgels in regenerative medicine.