CD301b(+) macrophages mediate angiogenesis of calcium phosphate bioceramics by CaN/NFATc1/VEGF axis

Calcium phosphate (CaP) bioceramics are important for tissue regeneration and immune response, yet how CaP bioceramics influence these biological processes remains unclear. Recently, the role of immune cells in biomaterial-mediated regeneration, especially macrophages, has been well concerned. CD301b(+) macrophages were a new subset of macrophages we have discovered, which were required for bioceramics-mediated bone regeneration. Nevertheless, the impact of CD301b(+) macrophages on angiogenesis, which is a vital prerequisite to bone formation is yet indistinct. Herein, we found that CD301b(+) macrophages were closely correlated to angiogenesis of CaP bioceramics. Additionally, depletion of CD301b(+) macrophages led to the failure of angiogenesis. We showed that store-operated Ca(2+) entry and calcineurin signals regulated the VEGF expression of CD301b(+) macrophages via the NFATc1/VEGF axis. Inhibition of calcineurin effectively impaired angiogenesis via decreasing the infiltration of CD301b(+) macrophages. These findings provided a potential immunomodulatory strategy to optimize the integration of angiogenesis and bone tissue engineering scaffold materials.