BMP4 peptide and enoxacin-loaded mesoporous silica nanoparticles direct cell fate and boost bone regeneration during infection

Bone related infections elicit excessive inflammatory responses, progressive osteolysis, and persistent bacterial load, which impede bone regeneration. Conventional antibiotics can mitigate bacterial load; however, they fail to inhibit bone resorption and the inflammatory response. To enhance bone regeneration during bacterial infection, an optimal therapeutic strategy should not only eradicate bacteria but also inhibit inflammation and osteolysis. In this study, we fabricated a multi-biofunctional coating, designated MSNs-BMP4-EN, by covalently immobilizing mesoporous silica nanoparticles (MSNs) with human bone morphogenetic protein 4 (BMP4) and loading with enoxacin (EN) for antibacterial effect with inhibiting inflammation and osteolysis. Antimicrobial assessments revealed that MSNs-BMP4-EN markedly obstructed bacterial adhesion and colonization. Subsequent in vitro assessments demonstrated that it facilitated osteogenic differentiation of bone mesenchymal stem cell and impeded early osteoclastogenesis. Moreover, MSNs-BMP4-EN effectively restrained the secretion of pro-inflammatory mediators, thereby counteracting the infection-induced inflammatory milieu and promoting bone regeneration. Collectively, these findings indicate that MSNs-BMP4-EN exhibits excellent antibacterial, anti-inflammatory, and bone resorption inhibitory attributes during initial stages of bone-related infection, thereby further improving bone regeneration. As a result, this bioactive nanocomposite has excellent prospects for treating bone infections.