Recent advances in mechanically strong and tough hyaluronic acid hydrogels and cryogels

Hyaluronic acid (HA) is a vital extracellular matrix component renowned for its exceptional hydration, lubrication, and biocompatibility. Despite widespread use, HA hydrogels suffer from poor mechanical strength and rapid degradation, restricting their load-bearing applications. This work reviews conventional cross-linking strategies targeting HA’s functional groups and highlights recent advances, particularly double-network (DN) and cryogelation methods that yield robust and resilient hydrogels and cryogels based on HA for advanced biomedical use. HA hydrogels with DN structures exhibit a fracture stress up to 12.2 MPa and a fracture strain of 94%, while the development of triple-network HA hydrogels enables resistance to compressive loads of 10–22 MPa at 95% strain, with Young’s modulus values reaching up to 1 MPa, the highest mechanical performance reported for HA hydrogels to date. Furthermore, macroporous HA cryogels exhibit unique properties such as tunable poroelasticity, reversible squeezability, nonswelling behavior, and high compressive strength (up to 2.6 ± 0.2 MPa), allowing control over network mesh size and enabling precision delivery of macromolecules. Collectively, these developments represent a significant leap in HA hydrogel research, opening new avenues for their use in load-bearing tissue engineering, controlled drug delivery, and regenerative medicine.