Recent Developments in Hyaluronic Acid-Based Hydrogels for Cartilage Tissue Engineering Applications

Articular cartilage lesions resulting from injurious impact, recurring loading, joint malalignment, etc., are very common and encompass the risk of evolving to serious cartilage diseases such as osteoarthritis. To date, cartilage injuries are typically treated via operative procedures such as autologous chondrocyte implantation (ACI), matrix-associated autologous chondrocyte implantation (MACI) and microfracture, which are characterized by low patient compliance. Accordingly, cartilage tissue engineering (CTE) has received a lot of interest. Cell-laden hydrogels are favorable candidates for cartilage repair since they resemble the native tissue environment and promote the formation of extracellular matrix. Various types of hydrogels have been developed so far for CTE applications based on both natural and synthetic biomaterials. Among these materials, hyaluronic acid (HA), a principal component of the cartilage tissue which can be easily modified and biofunctionalized, has been favored for the development of hydrogels since it interacts with cell surface receptors, supports the growth of chondrocytes and promotes the differentiation of mesenchymal stem cells to chondrocytes. The present work reviews the various types of HA-based hydrogels (e.g., in situ forming hydrogels, cryogels, microgels and three-dimensional (3D)-bioprinted hydrogel constructs) that have been used for cartilage repair, specially focusing on the results of their preclinical and clinical assessment.