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

Abstract

Guided bone regeneration in inflammatory microenvironments of osteoporotic patients with large alveolar bone defects remains a great challenge. Macrophages are necessary for alveolar bone regeneration <i>via</i> their polarization and paracrine actions. Our previous studies showed that Cu-bearing Ti6Al4V alloys are capable of regulating macrophage responses. When considering the complexity of oral microenvironments, the influences of Cu-bearing Ti6Al4V alloys on osteoporotic macrophages in infectious microenvironments are worthy of further investigations. In this study, we fabricated Ti6Al4V-Cu alloy by selective laser melting technology and used <i>Porphyromonas gingivalis</i> lipopolysaccharide (<i>P.g</i>-LPS) to imitate oral pathogenic bacterial infections. Then, we evaluated the impacts of Ti6Al4V-Cu on osteoporotic macrophages in infectious microenvironments. Our results indicated that Ti6Al4V-Cu not only inhibited the <i>P.g-</i>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 anti-inflammatory cytokine release. In addition, Ti6Al4V-Cu effectively promoted the activity of COMMD1 to potentially repress NF-κB-mediated transcription. It is concluded that the Cu-bearing Ti6Al4V 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.