Designing functional hyaluronic acid-based hydrogels for cartilage tissue engineering

Damage to cartilage tissues is often difficult to repair owing to chronic inflammation and a lack of bioactive factors. Therefore, developing bioactive materials, such as hydrogels acting as extracellular matrix mimics, that can inhibit the inflammatory microenvironment and promote cartilage repair is crucial. Hyaluronic acid, which exists in cartilage and synovial fluid, has been extensively investigated for cartilage tissue engineering because of its promotion of cell adhesion and proliferation, regulation of inflammation, and enhancement of cartilage regeneration. However, hyaluronic acid-based hydrogels have poor degradation rates and unfavorable mechanical properties, limiting their application in cartilage tissue engineering. Recently, various multifunctional hyaluronic acid-based hydrogels, including alkenyl, aldehyde, thiolated, phenolized, hydrazide, and host–guest group-modified hydrogels, have been extensively studied for use in cartilage tissue engineering. In this review, we summarize the recent progress in the multifunctional design of hyaluronic acid-based hydrogels and their application in cartilage tissue engineering. Moreover, we outline the future research prospects and directions in cartilage tissue regeneration. This would provide theoretical guidance for developing hyaluronic acid-based hydrogels with specific properties to satisfy the requirements of cartilage tissue repair.