Bioinspired collagen-gelatin-hyaluronic acid-chondroitin sulfate tetra-copolymer scaffold biomimicking native cartilage extracellular matrix facilitates chondrogenesis of human synovium-derived stem cells

The microenvironment plays a crucial role in stem cell differentiation, and a scaffold that mimics native cartilaginous extracellular components can promote chondrogenesis. In this study, a collagen–gelatin–hyaluronic acid–chondroitin sulfate tetra-copolymer scaffold with composition and architecture similar to those of hyaline cartilage was fabricated using a microfluidic technique and compared with a pure gelatin scaffold. The newly designed biomimetic scaffold had a swelling ratio of 1278 % ± 270 %, a porosity of 77.68 % ± 11.70 %, a compressive strength of 1005 ± 174 KPa, and showed a good resilience against compression force. Synovium-derived stem cells (SDSCs) seeded into the tetra-copolymer scaffold attached to the scaffold firmly and exhibited good mitochondrial activity, high cell survival with a pronounced glycosaminoglycan production. SDSCs cultured on the tetra-copolymer scaffold with chondrogenic induction exhibited upregulated mRNA expression of COL2A1, ChM-1, Nrf2, TGF-β1, and BMP-7. Ex vivo study revealed that the SDSC–tetra-copolymer scaffold regenerated cartilage-like tissue in SCID mice with abundant type II collagen and S-100 production. BMP7 and COL2A1 expression in the tetra-copolymer scaffold group was much higher than that in the gelatin scaffold group ex vivo. The tetra-copolymer scaffold thus exhibits strong chondrogenic capability and will facilitate cartilage tissue engineering. •A scaffold that mimics native cartilaginous ECM may facilitate chondrogenesis of stem cells.•Biomimetic tetra-copolymer scaffolds with high porosity and adequate mechanical strength were fabricated.•SDSCs cultured on the tetra-copolymer scaffold upregulated COL2A1, TGF-β1, and BMP-7 mRNA expression.•Ex vivo study revealed that the SDSC–tetra-copolymer scaffold regenerated cartilage-like tissue in SCID mice.•The tetra-copolymer scaffold with similar constituents to hyaline cartilage has strong chondrogenic capability.