In situ formation of nanostructured calcium phosphate coatings on porous hydroxyapatite scaffolds using a hydrothermal method and the effect on mesenchymal stem cell behavior

The micro/nano-structure of calcium phosphate has been demonstrated to play an essential role in determining cell behavior. However, it is difficult to fabricate micro/nano-structures on the surface of hydroxyapatite (HA) scaffolds. In this study, we have developed a new hydrothermal method for fabricating nanostructures on HA scaffolds with the assistance of 1,2,3,4,5,6-cyclohexanehexacarboxylic acid (H6L). We controlled the nanostructures of the calcium phosphate coatings deposited on the scaffolds by modulating the H6L concentration. The results demonstrated that with an increase in the H6L concentration, the calcium phosphate coatings gradually changed from plate-like, to wire-like, and further to spherical morphology. In vitro mesenchymal stem cell (MSC) culture indicated that cell differentiation was significantly enhanced when cultured on the spherical nanostructured coating compared with culture on a plate-like or wire-like nanostructure. Cell proliferation on coatings with different nanostructures was not statistically different with prolonged culture time. These findings indicate that different scaffold surface characteristics, including surface morphology and chemical properties, result in a significant difference in cell differentiation. The small molecule-assisted hydrothermal deposition method provides a simple and controllable route to engineer the nanostructure of HA scaffolds and to construct micro-environments for bone tissue engineering.