Preparation of Micro/Nano-Structure Copper-Substituted Hydroxyapatite Scaffolds with Improved Angiogenesis Capacity for Bone Regeneration

The surface microstructures of calcium phosphate ceramics play an essential role in determining bone regeneration. However, it is difficult to produce micro/nano-structures on the surface of the porous hydroxyapatite (HA) scaffolds. In this study, we successfully developed and fabricated various micro/nano-structured surfaces on the HA scaffolds in copper ion (Cu(2+))-containing solutions under hydrothermal conditions. The micro/nano-structures on the surface of the HA scaffolds were controlled by modulating the Cu(2+) concentrations during the hydrothermal process. With an increase in the Cu(2+) concentration, the surface morphology of the HA scaffolds changed significantly from sphere-like to flower-like, before becoming nano-structures. These findings indicated that the Cu(2+) concentration affects the morphologies of calcium phosphate coatings that grow on the HA scaffolds. In vitro endothelial cell (EC) cultures showed that the cell proliferation was significantly enhanced when cultured on the flower-like morphology compared with other morphologies. Furthermore, an in vivo test in New Zealand rabbits demonstrated that the HA scaffold with the flower-like surface resulted in more angiogenesis compared with the control scaffold. This copper-assisted hydrothermal deposition process provides a simple and controllable route for engineering a micro/nano-structured surface on the HA scaffolds, which has benefits in terms of angiogenesis and bone regeneration.