Sr-Incorporated Bioactive Glass Remodels the Immunological Microenvironment by Enhancing the Mitochondrial Function of Macrophage via the PI3K/AKT/mTOR Signaling Pathway

• DOI: 10.1021/acsbiomaterials.4c00228
• Publication Date: 2024-05-20T08:38:33Z
• Authors: Huanhuan Qiu; Huacui Xiong; Jiafu Zheng; Yuqi Peng; Chunhui Wang; Qing Hu; Fujian Zhao; Ke Chen
• Keywords: Bone Regeneration; Tissue Scaffolds; TOR Serine-Threonine Kinases; Macrophages; Biocompatible Materials; Mitochondria; Phosphatidylinositol 3-Kinases; Mice; RAW 264.7 Cells; Cellular Microenvironment; Strontium; Osteogenesis; Animals; Glass; Proto-Oncogene Proteins c-akt; Signal Transduction

The repair of critical-sized bone defects continues to pose a challenge in clinics. Strontium (Sr), recognized for its function in bone metabolism regulation, has shown potential in bone repair. However, the underlying mechanism through which Sr2+ guided favorable osteogenesis by modulating macrophages remains unclear, limiting their application in the design of bone biomaterials. Herein, Sr-incorporated bioactive glass (SrBG) was synthesized for further investigation. The release of Sr ions enhanced the immunomodulatory properties and osteogenic potential by modulating the polarization of macrophages toward the M2 phenotype. In vivo, a 3D-printed SrBG scaffold was fabricated and showed consistently improved bone regeneration by creating a prohealing immunological microenvironment. RNA sequencing was performed to explore the underlying mechanisms. It was found that Sr ions might enhance the mitochondrial function of macrophage by activating PI3K/AKT/mTOR signaling, thereby favoring osteogenesis. Our findings demonstrate the relationship between the immunomodulatory role of Sr ions and the mitochondrial function of macrophages. By focusing on the mitochondrial function of macrophages, Sr2+-mediated immunomodulation sheds light on the future design of biomaterials for tissue regenerative engineering.