Viscoelasticity microenvironment constructed by self-crosslinking hyaluronan hybrid hydrogels regulates chondrogenic differentiation of mesenchymal stem cells

Chondrogenic differentiation of stem cells can be regulated by mechanical properties of biomaterials. Here, hybrid hydrogels, composed of sulfhydrylated hyaluronan (HA-SH) with different molecular weight and collagen I (Col Ⅰ), were designed to investigate chondrogenic differentiation of rabbit bone marrow mesenchymal stem cells (rBMSCs). The enhanced molecular weight of HA-SH decreased the mechanical properties of hybrid hydrogels, but improved viscosity and degradation resistance, which could modulate cell spreading and morphological changes, thereby influencing chondrogenic differentiation. Furthermore, 1 MDa HA-SH combined with Col Ⅰ (1M-HAC) with adequate viscoelasticity was beneficial to the circularity and nuclear chromatin condensation of rBMSCs, which induced significant chondrocyte aggregation, increased glycosaminoglycans and collagen Ⅱ stainings, and reduced collagen Ⅹ staining. This was conducive to preserve a hyaline cartilage's phenotype and reducing inflammation and degeneration. Subcutaneous implantation studies revealed that 1M-HAC also facilitated specific matrix secretion, chondrogenic gene expression and potentially anti-inflammatory and anti-degenerative effects.