A murine distal femoral epiphysis ischemia model reveals spatiotemporal stratification of necrotic bone marrow clearance and associated inflammatory responses

The JIO necrosis-repair interface adheres to a distinct spatiotemporal program in which apoptotic cells transition into secondary necrosis concurrently with revascularization efforts. Cells undergoing secondary necrosis are subsequently eliminated during the fibrovascular replacement processes. Notably, neutrophil-derived MPO spatially associates with M1-skewed macrophages in vivo and enhances M1 polarization in vitro; this suggests an immunoregulatory axis exists between neutrophils and macrophages at the interface. Strategies aimed at enhancing the clearance of secondary necrosis neutrophils and modulating this axis may facilitate inflammatory resolution and improve epiphyseal repair.