Composite systems based on hyaluronic acid and natural polysaccharides for cartilage and bone tissue regeneration: An updated review

Abstract

The repair of cartilage and bone defects, both structurally and functionally, remains a significant challenge. Traditional treatment methods, such as autogenous and allogeneic bone grafts, face limitations, including issues of availability, cost, immune rejection, and other concerns, making them insufficient to fully address clinical needs. As a result, the integration of biomaterials with tissue engineering strategies has emerged as a promising research direction. Among various materials, hydrogels have attracted considerable attention due to their biological activity, degradability, absorbability, plasticity, and ease of preparation. Hyaluronic acid (HA), a key natural polysaccharide and a major constituent of the extracellular matrix (ECM), has been extensively applied in tissue healing and regeneration because of its excellent biocompatibility, biodegradability, bioactivity, and the availability of reactive functional groups for modification. In particular, HA-composed hydrogels, compared to typical hydrogels, provide a highly adaptable structure and a tissue-mimetic microenvironment that closely resembles the ECM, thereby supporting and enhancing tissue repair and regeneration. In this review, we have discussed the mechanisms through which HA-based hydrogels promote ECM formation in cartilage and bone, their combination with other natural polymers, hyaluronic acid composited injectable hydrogel and the application of 3D bio-printed HA hydrogels for effective cartilage and bone regeneration.