Abstract
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.
Highlights
Articular cartilage is a glass-like tissue that lines the ends of articulating bones
Regardless of the numerous hyaluronic acid (HA)-based hydrogels that have been developed for the repair of cartilage defects and have shown encouraging results in in vitro and in vivo tests, only one medicinal product (Cartistem® ) comprising culture-expanded allogeneic human umbilical-cord-blood-derived mesenchymal stem cells and an HA hydrogel has been evaluated in phase I/II [103,104] and III [105] clinical trials for its ability to regenerate cartilage tissue
Numerous human mesenchymal stem cells (hMSCs)- or chondrocyte-laden HA-based injectable hydrogels and 3D-bioprinted hydrogel constructs of various compositions and functional groups, exhibiting variable rheological/mechanical properties and encapsulating or not bioactive molecules, have been developed and preclinically assessed during the last decade regarding their possible utilization in the regeneration of injured cartilage tissue
Summary
Articular cartilage is a glass-like tissue that lines the ends of articulating bones. [6,7]) with well-known drawbacks (e.g., ACI can possibly result in scarring, postoperative morbidity, generation of cartilage tissue with inferior biomechanical properties in comparison with the native tissue and at risk of breaking down and requiring total joint arthroplasty, etc.) [1] In this respect, hydrogel-aided cartilage tissue engineering (CTE) could be considered a promising alternative solution for cartilage repair. Hydrogels are three-dimensional, highly water-swollen networks characterized by adjustable rheological/mechanical properties, biocompatibility, biodegradability and masstransfer ability (i.e., they facilitate the exchange of oxygen and soluble molecules) [8]. They can be formed using natural or synthetic polymeric materials, or a combination of them (i.e., hybrid or composite hydrogels). Review and research papers addressing the in vitro and in vivo assessment of different types of HA hydrogels in CTE as well as related material addressing the clinical evaluation of HA hydrogels were thoroughly assessed and selected for inclusion
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