In vitro Chondrocyte Responses in Mg-doped Wollastonite/Hydrogel Composite Scaffolds for Osteochondral Interface Regeneration.

The zone of calcified cartilage (ZCC) is the mineralized region between the hyaline cartilage and subchondral bone and is critical in cartilage repair. A new non-stoichiometric calcium silicate (10% Ca substituted by Mg; CSi-Mg10) has been demonstrated to be highly bioactive in an osteogenic environment in vivo. This study is aimed to systematically evaluate the potential to regenerate osteochondral interface with different amount of Ca-Mg silicate in hydrogel-based scaffolds, and to compare with the scaffolds containing conventional Ca-phosphate biomaterials. Hydrogel-based porous scaffolds combined with 0-6% CSi-Mg10, 6% β-tricalcium phosphate (β-TCP) or 6% nanohydroxyapatite (nHAp) were made with three-dimensional (3D) printing. An increase in CSi-Mg10 content is desirable for promoting the hypertrophy and mineralization of chondrocytes, as well as cell proliferation and matrix deposition. Osteogenic and chondrogenic induction were both up-regulated in a dose-dependent manner. In comparison with the scaffolds containing 6% β-TCP or nHAp, human deep zone chondrocytes (hDZCs) seeded on CSi-Mg10 scaffold of equivalent concentration exhibited higher mineralization. It is noteworthy that the hDZCs in the 6% CSi-Mg10 scaffolds maintained a higher expression of the calcified cartilage zone specific extracellular matrix marker and hypertrophic marker, collagen type X. Immunohistochemical and Alizarin Red staining reconfirmed these findings. The study demonstrated that hydrogel-based hybrid scaffolds containing 6% CSi-Mg10 are particularly desirable for inducing the formation of calcified cartilage.