A multifunctional composite scaffold responds to microenvironment and guides osteogenesis for the repair of infected bone defects

Abstract Treating bone defect concomitant with microbial infection poses a formidable clinical challenge. Addressing this dilemma necessitates the implementation of biomaterials exhibiting dual capabilities in anti-bacteria and bone regeneration. Of particular significance is the altered microenvironment observed in infected bones, characterized by acidity, inflammation, and an abundance of reactive oxygen species (ROS). These conditions, while challenging, present an opportunity for therapeutic intervention in the context of contaminated bone defects. In this study, we developed an oriented composite scaffold containing copper-coated manganese dioxide (MnO2) nanoparticles loaded with parathyroid hormone (PMPC/Gelatin). The characteristics of these scaffolds were meticulously evaluated and confirmed the high sensitivity to H+, responsive drug release and ROS elimination. In vitro antibacterial analysis underscored the remarkable ability of PMPC/Gelatin scaffolds to substantially suppressed bacterial proliferation and colony formation. Furthermore, this nontoxic material demonstrated efficacy in mitigating ROS levels, thereby fostering osteogenic differentiation of bone marrow mesenchymal stem cells and enhancing angiogenic ability. Subsequently, the infected models of bone defects in rat skulls were established to investigate the effects of composite scaffolds on anti-bacteria and bone formation in vivo. The PMPC/Gelatin treatment exhibited excellent antibacterial activity, coupled with enhanced vascularization and osteogenesis at the defect sites. These compelling findings affirm that the PMPC/Gelatin composite scaffold represents a promising avenue for anti-bacteria and bone regeneration.