Functionalized TiCu/Ti-Cu-N-Coated 3D-Printed Porous Ti6Al4V Scaffold Promotes Bone Regeneration through BMSC Recruitment

Ti6Al4V scaffolds have high strength and corrosion resistance. 3D printing technology can optimize the pore structure of Ti6Al4V scaffolds, promoting bone tissue growth into the scaffolds to form firm osseointegrations. However, Ti6Al4V lacks biological activity. This defect can be overcome through surface modifications. Arc ion plating is employed to prepare titanium copper/titanium copper nitride (TiCu/Ti-Cu-N) multilayer coating, which is applied to 3D-printed porous Ti6Al4V scaffolds by selective laser melting and bearing 300-400 mu m pores. In addition to the excellent biological activity of copper, TiN shows superior corrosion resistance. The scaffold properties, osteogenesis, and osteointegration are evaluated in vitro and in vivo. Results show that human bone mesenchymal stem cells (hBMSCs) proliferate and adhere more effectively on coated scaffolds than on uncoated scaffolds. Further, the coating has a significant role in recruiting hBMSCs, and upregulation of the SDF-1 alpha/CXCR4 axis, p38 expression, and extracellular signal-related kinase (Erk) and Akt signaling pathway. The in vitro results are further confirmed by an animal experiment in the New Zealand white rabbit femur tibia defect. Overall, the TiCu/Ti-Cu-N-coated 3D-printed Ti6Al4V scaffold shows excellent biocompatibility and bioactivity in promoting bone repair. The underlying mechanism may involve recruiting BMSCs and promoting their osteogenic differentiation.