Mollusk Shell-Derived Chitin-Enhanced Hydrogel Scaffolds with Dual-Cross-Linking Biomimetic Networks for Phenotype-Stable Cartilage Regeneration

The development of a scaffold that mimics the natural composition and function of the cartilage extracellular matrix is essential for effectively repairing articular cartilage damage. In this study, an aldehyde-based methacrylate hyaluronic acid (AHAMA) hydrogel was integrated with a polydopamine (pDA)-modified mollusk shell-derived organic template (OTMS), thus successfully combining natural biomass materials with a hydrogel for cartilage defect repair for the first time. The OTMS/pDA/AHAMA composite scaffold features a natural three-dimensional porous network with a uniform pore size distribution, promoting cell and tissue infiltration. AHAMA hydrogel was attached to the surfaces of OTMS/pDA and cartilage surfaces via Schiff-base reactions and hydrogen bonding, establishing a biocompatible niche that supports cellular growth and differentiation. OTMS, composed primarily of natural chitin, provides biological signals that stimulate cartilage regeneration and offer excellent biocompatibility. The compressive characteristics of the hydrogel were dramatically boosted by the introduction of OTMS into the composite scaffold structure. The OTMS/pDA/AHAMA composite scaffold exhibited excellent biocompatibility in vitro, as evidenced by enhanced chondrocyte adhesion and proliferation, elevated expression of chondrogenic genes, and stable maintenance of the differentiated phenotype, indicating its promise for cartilage repair applications.