Rasoulian, F.; Ghaffari-Bohlouli, P.; Otahal, A.; Bauer, C.; Shahabi Nejad, M.; Klein, M.; Shavandi, A.; Heydari, A.; Nehrer, S.

Articular cartilage has limited self-repair capacity, and current treatments fail to fully restore its structure and function. 3D hydrogels that support chondrocyte viability and extracellular matrix (ECM) deposition offer a promising strategy for cartilage regeneration. Here, we developed a photo-crosslinkable silk fibroin/hyaluronic acid hydrogel for 3D encapsulation of primary human chondrocytes. Hydrogels were formulated with varying silk fibroin methacrylate (SilMA, 10/20% w/v) and hyaluronic acid methacrylate (HAMA, 1/2% w/v) concentrations and characterized for rheological, mechanical, and morphological properties. All SilMA/HAMA hydrogel formulations exhibited shear-thinning behavior and rapidly gelled (<20 s) under UV irradiation while maintaining high porosity, thereby ensuring injectability and efficient nutrient diffusion. Notably, the Youngs modulus of the cell laden scaffolds increased from ~18 kPa to ~1200 kPa over culture, indicating mechanical maturation driven by chondrocyte-mediated matrix deposition. This maturation was further confirmed by histological analysis and qPCR, which demonstrated enhanced ECM production and chondrogenic gene expression. Taken together, these results highlight SilMA/HAMA hydrogels as a promising biomimetic platform that couples mechanical reinforcement with biological functionality for cartilage tissue engineering.