Macrophage membrane functionalized composite microspheres promote bone regeneration in periodontitis via manipulating inflammation reversing-osteogenesis coupling

Periodontitis is characterized by inflammation and alveolar bone loss, primarily caused by immune cells activated by oral bacteria, leading to an imbalance between osteogenesis and bone resorption. Traditional treatments have limited efficacy, which has led to the exploration of regulating the immune microenvironment and utilizing tissue engineering methods as new research directions. Our study demonstrates that macrophage membranes, activated by LPS and IFN-γ, can effectively neutralize inflammatory factors. By coating the poly-L-lysine (PLL) modified poly (lactic-co-glycolic acid) (PLGA)/β-TCP microspheres with such macrophage membrane vesicles, the MM@PPT microspheres regulate intercellular responses by inhibiting macrophage M1 polarization and osteoclast differentiation, promoting M2 polarization, and enhancing osteogenic differentiation of bone marrow stromal cells (BMSCs) even in an inflammatory environment. By injecting the MM@PPT into sites of periodontitis induced bone resorption, it is found that they can effectively promote bone regeneration by modulating the immune-regeneration microenvironment. This work not only highlights the potential of MM@PPT microspheres in promoting alveolar bone regeneration but also provides insights into how these microspheres modulate cell behavior and interactions. The findings of this study offer novel therapeutic strategies for promoting alveolar bone repair in periodontitis.