Composite Coating of Graphene Oxide/TiO₂ Nanotubes/HHC-36 Antibacterial Peptide Construction and an Exploration of Its Bacteriostat and Osteogenesis Effects.

Abstract

Graphene oxide (GO), a kind of polymer, is often selected as a controlled released agent, whereas titanium dioxide (TiO₂) nanotubes are commonly used as a drug-coated carrier. This study was conducted to develop methods for manufacturing the GO/TiO₂/HHC-36 composite coating and exploring its bacteriostat and osteogenesis properties. The GO/TiO₂ nanotubes were prepared by electrochemical methods and HHC-36 was then adsorbed to GO/TiO₂to obtain GO/TiO₂/HHC-36. Sustained release of HHC-36 was analyzed and the antibacterial effect was examined by the inhibition zone test. The biocompatibility and osteogenesis in vitro of GO/TiO₂/HHC-36 were explored. Finally, the osteogenesic property of the composite coating was investigated in a rat femoral defect model in vivo. GO/TiO₂/HHC-36 was successfully prepared and had good controlled released performance in vitro. The inhibit zone size of S. aureus was 2.1 mm and that of E. coli was 3.0 mm. GO/TiO₂/HHC-36 showed good biocompatibility with mesenchymal stem cells (MSCs) and promoted their adhesion, migration, and differentiation. In addition, the secretion of alkaline phosphatase, collagen, mineralized matrix and osteoblast-related nutrient factors of MSCs was increased after treatment with GO/TiO₂/HHC-36. Furthermore, GO/TiO₂/HHC-36 also stimulated endotheliocytes to secrete VEGF, leading to angiogenesis. Finally, implantation of GO/TiO₂/HHC-36 in the rat femur defect model resulted in MSC migration and increased expression of osteoblast related proteins. The composite coating with controlled released of HHC-36 showed distinct antibacterial properties and promoted osteogenesis in vitro and in vivo.