Osteogenic Induction and Anti‐Inflammatory Effects of Calcium‐Chlorogenic Acid Nanoparticles Remodel the Osteoimmunology Microenvironment for Accelerating Bone Repair

Successful bone regeneration requires close cooperation between bone marrow mesenchymal stem cells (BMSCs) and macrophages, but the low osteogenic differentiation efficiency of stem cells and the excessive inflammatory response of immune cells hinder the development of bone repair. It is necessary to develop a strategy that simultaneously regulates the osteogenic differentiation of BMSCs and the anti-inflammatory polarization of macrophages for accelerating the bone regeneration. Herein, calcium-chlorogenic acid nanoparticles (Ca-CGA NPs) are synthesized by combining the small molecules of chlorogenic acid (CGA) with Ca²⁺. Ca-CGA NPs internalized by cells can be dissolved to release free CGA and Ca²⁺ under low pH conditions in lysosomes. In vitro results demonstrate that Ca-CGA NPs can not only enhance the osteogenic differentiation of BMSCs but also promote the phenotype transformation of macrophages from M1 to M2. Furthermore, in vivo experiments confirm that Ca-CGA NPs treatment facilitates the recovery of rat skull defect model through both osteoinduction and immunomodulation. This study develops a new Ca-CGA NPs-based strategy to induce the differentiation of BMSCs into osteoblasts and the polarization of macrophages into M2 phenotype, which is promising for accelerating bone repair.