Tuning osteoporotic macrophage responses to favour regeneration by Cu-bearing titanium alloy in Porphyromonas gingivalis lipopolysaccharide-induced microenvironments

Guided bone regeneration in inflammatory microenvironments of osteoporotic patients with large alve-olar bone defects remains a great challenge.Macrophages are necessary for alveolar bone regeneration via their polarization and paracrine actions.Our previous studies showed that Cu-bearing Ti6AI4V alloys are capable of regulating macrophage responses.When considering the complexity of oral microenvir-onments,the influences of Cu-bearing Ti6AI4V alloys on osteoporotic macrophages in infectious microenvironments are worthy of further investigations.In this study,we fabricated Ti6AI4V-Cu alloy by selective laser melting technology and used Porphyromonas gingivalis lipopolysaccharide(P.g-LPS)to imitate oral pathogenic bacterial infections.Then,we evaluated the impacts of T6AI4V-Cu on osteoporotic macrophages in infectious microenvironments.Our results indicated that Ti6AI4V-Cu not only inhibited the P.g-LPS-induced M1 polarization and pro-inflammatory cytokine production of osteoporotic macrophages but also shifted polarization towards the pro-regenerative M2 phenotype and remarkably promoted antinflammatory cytokine release.In addition,T6AI4V-Cu effectively promoted the actity of COMMD1 to potentially repress NF-κB-mediated transcription.It is concluded that the Cubearing Ti6AI4V alloy results in ameliorated osteoporotic macrophage responses to create a favourable microenvironment under infectious conditions,which holds promise to develop a GBR-barrier membrane for alveolar bone regeneration of osteoporosis patients.