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 1MHAC also facilitated specific matrix secretion, chondrogenic gene expression and potentially anti-inflammatory and anti-degenerative effects.

Automated summary

This study designed hybrid hydrogels composed of sulfhydrylated hyaluronan (HA-SH) with different molecular weight and collagen I (Col I) to investigate the chondrogenic differentiation of rabbit bone marrow mesenchymal stem cells (rBMSCs). The increase in molecular weight of HA-SH decreased the mechanical properties of the hydrogels but improved viscosity and degradation resistance, thereby modulating cell spreading and morphological changes and influencing chondrogenic differentiation. The combination of 1 MDa HA-SH and Col I (1M-HAC) with adequate viscoelasticity was found to be beneficial for the circularity and nuclear chromatin condensation of rBMSCs, inducing significant chondrocyte aggregation and promoting the production of glycosaminoglycans and collagen II.