Exosomes derived from macrophages upon cobalt ion stimulation promote angiogenesis

Angiogenesis is critical for tissue repair and regeneration, including implant osseointegration. It is well known that macrophages exert immunomodulatory functions in angiogenesis. However, whether macrophage-derived exosomes participate in the process is still unclear. Cobalt (Co) ions are frequently used as implant additives to mimic hypoxic microenvironment, which can induce angiogenesis through stabilizing hypoxia inducible factor-1α (HIF-1α) of macrophages and endothelial cells (ECs). The present work attempts to investigate whether exosomes derived from macrophages upon Co ion stimulation can mediate angiogenesis and the possible mechanism. The results show that the exosomes promote endothelial migration and angiogenesis in vitro and in vivo, particularly when Co ion concentration is 200 μM. Further studies reveal that the exosomes upregulating nitric oxide (NO), vascular endothelial growth factor (VEGF), and integrin β1 expression may be the underlying mechanism of the observations. Our findings provide new insights for Co ion mediated macrophage-EC communication and surface design of biomaterials from the perspective of pro-angiogenesis.