Bioengineered Silk Fibroin/Hyaluronic Acid Composite Hydrogel for Minimally Invasive Cartilage Repair

With the growing global burden of cartilage degeneration in aging populations and the limitations of conventional surgical interventions, tissue-engineered hydrogels have emerged as a transformative strategy for functional cartilage regeneration. Here, we report an innovative bioinspired composite hydrogel fabricated through carbodiimide-mediated crosslinking of silk fibroin (SF) and hyaluronic acid (HA) using 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (EDC)/N-hydroxysuccinimide (NHS) in MES buffer. The engineered hydrogel exhibited an optimally interconnected porous architecture (pore size: 50-100 μm), tunable compressive modulus ( 86.51 KPa mimicking native cartilage), and swelling performance (570 ± 15%), addressing critical requirements for minimally invasive delivery and mechanical stability. Comprehensive in vitro characterization demonstrated exceptional cytocompatibility, with close to 100% hBMSC viability over 7 days. Most notably, the SF/HA hydrogel significantly promoted chondrogenic differentiation, as evidenced by: (1) 1.8 fold increased in progressive glycosaminoglycan (GAG) deposition (Alcian blue staining), (2) upregulation of SOX9, COL2, and AGG gene expression (RT-qPCR, 1.4, 0.4 and 1.3 fold vs. control), and (3) enhanced type II collagen synthesis (Western blot). These results demonstrate the potential of SF/HA hydrogel for cell-based cartilage repair and osteoarthritis therapy.