Copper-modified Ti6Al4V alloy fabricated by selective laser melting with pro-angiogenic and anti-inflammatory properties for potential guided bone regeneration applications

Custom-made biocompatible titanium alloy mesh can be designed to facilitate the regeneration of alveolar bone defects by supporting a protected space and inhibiting bacterial infections. Copper ions are often incorporated into titanium alloy due to their high bioactivity and outstanding antibacterial properties. However, the impacts of copper-bearing alloys on peri-implanted cell behaviors have rarely been systematically explored. In the present study, a copper-bearing alloy (Ti6Al4V-6Cu) was fabricated by selective laser melting (SLM) technology. The characterization of Ti6Al4V-6Cu alloy and its effects on the behaviors of gingival fibroblasts (HGFs), human umbilical vein endothelial cells (HUVECs), osteoblasts and macrophages were evaluated and compared with Ti6Al4V. The diffraction peaks of the Ti2Cu intermetallic phase were observed in the Ti6Al4V-6Cu alloy. Adding Cu enhanced the release of Ti and Al ions. The chemical state of Cu in the Ti6A14V-6Cu alloy may exist predominantly in Cu2O or TiCuOx. Ti6Al4V-6Cu did not affect the attachment of HGFs or the osteogenic activity of osteoblasts. Furthermore, it inhibited the activation, proliferation, and pro-inflammatory cytokine secretion of macrophages and upregulated angiogenesis-related gene expression and VEGF-A secretion of HUVECs. These results demonstrate that a Ti6Al4V-6Cu alloy was successfully fabricated that did not negatively impact the cell viability of gingival fibroblasts and osteoblasts, inhibited the inflammatory response of macrophages, and increased the angiogenesis of HUVECs. Thus, Ti6Al4V-6Cu has potential applications for the fabrication of titanium alloy mesh to promote alveolar bone regeneration.