Exogenous M2 Macrophage‐Loaded Scaffolds Promote Early Periodontal Regeneration by Improving Osteogenic Differentiation, Cell Homing, and Angiogenesis

Abstract Manipulating the immune microenvironment (including the macrophage phenotype) by tissue implants is an important direction in the field of tissue regeneration. This study reports a macrophage‐loaded hybrid scaffold construction to improve the response efficiency of implant–macrophage–tissue regeneration axis and precisely polarize macrophages toward the pro‐regenerative M2 phenotype in vitro, and constructed an M2 macrophage‐loaded hybrid scaffold. The feasibility of using a macrophage‐loaded hybrid scaffold for immune‐mediated periodontal regeneration is studied in vivo and in vitro. The results illustrate that the M2 macrophage‐loaded hybrid scaffolds promoted the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) in vitro and promoted cell recruitment and angiogenesis in vivo to perform well in early in vivo osteogenesis. The macrophage‐loaded hybrid scaffold proposed in this study plays an important role in promoting periodontal regeneration, which enriches the theory and strategy of macrophage phenotype regulation‐mediated periodontal regeneration, and provides inspiration and reference for using macrophage‐loaded hybrid scaffolds in regenerating other tissues.