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.
Keywords: Chondral defect regeneration; Human adipose-derived stem cells (hADSCs); Hyaluronan (HA) microenvironment.
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