Icariin conjugated hyaluronic acid/collagen hydrogel for osteochondral interface restoration

Over the past decades, numerous tissue-engineered constructs have been investigated for the osteochondral repair. However, it still remains a challenge to regenerate the functionalized calcified layer. In this study, the potential of icariin (Ica) conjugated hyaluronic acid/collagen (Ica-HA/Col) hydrogel to promote the osteochondral interface restoration was investigated. Compared with HA/Col hydrogel, Ica-HA/Col hydrogel simultaneously facilitated chondrogenesis and osteogenesis in vitro. The cells encapsulated in Ica-HA/Col hydrogel tended to aggregate into bigger clusters. The chondrogenic genes' expression level was remarkably up-regulated, and the matrix synthesis of sGAG and type II collagen was significantly enhanced. Similarly, the osteogenic genes, including RUNX2, ALP, and OCN were also up-regulated at early stage. Consequently, more calcium deposition was observed in the Ica-HA/Col hydrogel construct. Moreover, the gene expression and matrix synthesis of type X collagen, an important marker for the formation of calcified layer; were significantly higher in the Ica-HA/Col hydrogel. Furthermore, the in vivo study showed that Ica-HA/Col constructs facilitated the reconstruction of osteochondral interface in rabbit subchondral defects. In the Ica-HA/Col group, the neo-cartilage layer contained more type II collagen and the newly formed subchondral bone deposited more abundant type I collagen. Overall, the results indicated that Ica-HA/Col hydrogel might be a promising scaffold to reconstruct an osteochondral interface, therefore promoting restoring of osteochondral defect.

The osteochondral defect restoration not only involves the repair of damaged cartilage and the subchondral bone, but also the reconstruction of osteochondral interface (the functional calcified layer). The calcified layer regeneration is essential for integrative and functional osteochondral repair. Over the past decade, numerous tissue engineered constructs have been investigated for the osteochondral repair. However, it still remains a challenge to regenerate a functionalized calcified layer. The present study demonstrates that Ica-HA/Col hydrogel facilitates deposition of matrix related to calcified layer in mixed chondrogenic/osteogenic inductive media and restoration of osteochondral defect in vivo. Since, Ica-HA/Col hydrogel as is cheaper, easier and more efficient, it might be a desired scaffold for the osteochondral defects restoration.