Scaffold Curvature Promoting Bone Regeneration Through Itgb1-Mediated Macrophage Polarization

The repair of critical-sized bone defects remains a major challenge in the medical field, significantly impacting patients' quality of life. M2 macrophages within the osteoimmune microenvironment play a crucial role in bone regeneration. Recent studies have demonstrated that scaffold curvature, a clinically translatable structural feature, has shown remarkable potential in promoting angiogenesis and bone regeneration. However, the mechanisms underlying its regulation of the osteoimmune microenvironment remain unclear. This study focuses on this critical issue, aiming to elucidate how scaffold curvature facilitates bone regeneration by modulating M2 macrophage polarization. Previous studies have confirmed that integrin beta-1 (ITGB1)-mediated mechanotransduction signaling plays a pivotal role in scaffold curvature-regulated macrophage polarization. Subsequent research will employ myeloid-specific Itgb1 knockout mouse models, combined with in vivo and in vitro experiments, multi-omics analysis, and molecular biology techniques, to systematically validate the role of the downstream ITGB1-PI3K-AKT-PKM signaling pathway in regulating M2 macrophage polarization through PKM2-mediated glycolysis and nuclear translocation. Additionally, an indirect co-culture system will be established to investigate the paracrine effects of macrophages on osteogenic differentiation and evaluate bone regeneration efficacy. The larger curvature of structure promotes M2 polarization of macrophages through glycolysis/nuclear translocation of ITGB1-PI3K-AKT-PKM2, and its paracrine pathway promotes osteogenic differentiation and mineralization, thus promoting bone regeneration. This study will elucidate the mechanism by which scaffold curvature mediates macrophage M2 polarization through ITGB1, providing important theoretical basis and potential intervention targets for optimizing the design of bone implant materials.