The synergistic regulation of chondrogenesis by collagen-based hydrogels and cell co-culture

The suitable seeding cells and scaffolds are very important for tissue engineering to create functional cartilage. Although the physicochemical properties of scaffold and co-culture system of mesenchymal stem cells (MSCs) and chondrocytes could affect functional properties of engineered cartilage tissues respectively, the combined effects of them on chondrogenesis is currently unknown. Herein, methacrylated collagen (CMA30 and CMA80) hydrogels with different degradation rate and stiffness were prepared. The MSCs and chondrocytes were co-cultured or monocultured in collagen, CMA30 and CMA80 hydrogels in vitro or in vivo. The results demonstrated that cell spreading and proliferation was regulated by degradation rate and stiffness of hydrogels. Compared to single MSCs culture, co-culture cells in all collagen-based hydrogels significantly improving chondrogenesis. CMA30 hydrogels with moderate degradation rate and softest matrix were the most effective for co-culture system to promote chondrogenesis compared to Col and CMA80 in vitro culture, while there was no obvious difference between CMA30 and CMA80 in vivo. Furthermore, the intercellular material exchange was very important for co-culture system to maintain the positive effect on chondrogenesis. Overall, the current study highlights the synergistic effects of the physicochemical properties of collagen-based hydrogel and co-culture system on cartilage formation and provides a promising strategy for cartilage tissue engineering. STATEMENT OF SIGNIFICANCE: The suitable seeding cells and scaffolds are very important for tissue engineering. Although the collagen hydrogel, mesenchymal stem cells (MSCs) and chondrocytes has important applications in cartilage repair, the combined effects of physicochemical properties of collagen hydrogel and co-culture system (MSCs and chondrocytes) on chondrogenesis is unknown. In contrast to the studies that investigated the effect of a single factor (scaffolds or cells) on cartilage formation, this manuscript explored the role of both scaffold properties and biological factors on chondrogenesis. The current study highlights the synergistic effects of the matrix stiffness and degradation rate of collagen-based hydrogels and co-culture system on chondrogenesis and provided a promising strategy for cartilage regeneration by tissue engineering.

Cell co-culture; Chondrogenesis; Collagen-based hydrogel; Tissue engineering.