Hyaluronan microenvironment enhances cartilage regeneration of human adipose-derived stem cells in a chondral defect model

Hyaluronan (HA) is an important extracellular matrix component in the early stage of chondrogenesis. This study aimed to investigate the application of an HA microenvironment for human adipose-derived stem cells (hADSCs)-based articular cartilage regeneration. HA-enriched fibrin (HA/Fibrin) hydrogels were synthesized and characterized for use as HA microenvironments. The cell viability and chondrogenic gene expression of hADSCs cultured in HA/Fibrin (HA/Fibrin/hADSC) and Fibrin (Fibrin/hADSC) hydrogels were tested in vitro. A chondral defect created in osteochondral core explants ex vivo was used to test chondral defect regeneration by HA/Fibrin/hADSC or Fibrin/hADSC hydrogels. The results showed that HA/Fibrin hydrogels exhibited an increased swelling ratio and matrix stiffness and a smoother surface with more interconnected pores than in Fibrin hydrogels. The viability of hADSCs in HA/Fibrin/hADSC hydrogels was not altered, but they exhibited higher chondrogenic gene expression than those in Fibrin/hADSC hydrogels. For chondral defect regeneration, the HA/Fibrin/hADSC hydrogels exhibited the most cartilaginous tissue neo-formation, chondral integration and sGAG content in the surrounding tissue. This study demonstrated that an HA microenvironment enhances hADSC-mediated cartilage regeneration in chondral defects and thus may be used for ADSC-based articular cartilage tissue engineering.