Silk-hyaluronic acid bioinks recreate a dynamic chondrogenic niche for stem cell differentiation and matrix-driven maturation in bioprinted cartilage models

Progress in cartilage engineering requires advanced tissue models capable of replicating the structural and cellular organisation of native tissue whilst supporting extracellular matrix (ECM) remodelling and functional tissue maturation. In this study, methacrylated silk fibroin (SFMA) and hyaluronic acid (HAMA) were combined into a dual-component, photopolimerisable biomaterial ink designed to recreate the biochemical composition and mechanical dynamics of the native cartilage ECM in bioprinted constructs. HAMA incorporation produced a denser, structurally stable hydrogel system, supporting longterm stem cell viability and a rounded, chondrocyte-like cell morphology. SFMA-HAMA hydrogels consistently promoted higher expression of chondrogenic markers -SOX9, COL2A1, and ACAN -and suppressed COL1A2 compared to SFMA, and supported deposition of a hyaline-like matrix rich in sulphated glycosaminoglycans, collagen type II, and hyaluronic acid. Time-resolved mechanical analysis revealed progressive stiffening of cell-laden SFMA-HAMA constructs over 28 days, driven by matrix deposition and hydrogel network reorganisation, distinct from the intrinsic material stiffening observed in SFMA hydrogels. Bioprinted constructs maintained robust chondrogenic potential and construct shape fidelity following fabrication. This work demonstrates that SFMA-HAMA bioinks recreate a dynamic chondrogenic niche capable of directing stem cell chondrogenesis and supporting cell-mediated matrix remodelling and construct maturation -paving the way for more physiologically relevant bioprinted platforms for studying cartilage biology, disease modelling, and the development of innovative regenerative therapies.