An electroporation strategy to synthesize the membrane-coated nanoparticles for enhanced anti-inflammation therapy in bone infection

The cell membrane-coated nanoparticles (MNPs) showed great potential in treating infectious disease due to their superior biofunctions in improving biocompatibility of nanoparticles and neutralization of pathogen or toxins. However, bone infection is accompanied with severe inflammation and bone loss, which also requires anti-inflammatory and osteoconductive treatment. The conventional membrane coating method has to undergo ultrasonication and extrusion procedures, which reduces the functionality of cell membrane and limits the choice of nanoparticles. In this study, we proposed an electroporation-based membrane coating strategy to facilitate the synthesis of MNPs to tackle those problems. Methods: Magnetic composite nanoparticles with osteoconductive Ca3(PO4)2 and bactericidal TiO2 were assembled into macrophages through phagocytosis and then collected to expose in electric field for obtaining macrophage membrane-coating nanoparticles. By using molecular dynamics simulation and materials characterizations, the cell membrane coating efficiency was confirmed. The in vitro anti-bacterial and anti-inflammatory abilities were tested by bacteria culturing and immune cells activation. Then drug-resistant bacteria induced bone infection model was established to verify its in vivo therapeutic effects. Results: The coated membrane prepared through electroporation reserved the integrality of membrane structure and right-sidedness, with more functional proteins. Those led to the superior properties of recognition and adsorption with bacteria, toxins and inflammatory cytokines. Owing to the benefits of electroporation, the MNPs exhibited significant better antibacterial and anti-inflammatory abilities for enhancing the tissue repair process. Conclusion: This study provides a novel self-assembly cell membrane coating strategy by electroporation to construct multifunctional membrane-coating nanoparticles for bone infection treatment. This strategy not only improves the functions of coated membrane, but is also proved to be universal for varies nanoparticles or cells, indicating a great potential for future applications in the bioengineering field.