Copper, a frequently used additive of implant materials, can alter macrophage phenotype thus directing the fate of the implants. Exosomes, secreted by mammalian cells, can target to recipient cells and mediate their functions. However, whether exosomes derived from macrophages upon copper ion stimulation can modulate angiogenesis, a key index for implant osseointegration, is still unclear. Herein, the influence of copper ions on macrophage-derived exosome secretion, ingestion behavior by endothelial cells, and angiogenic-induction ability is investigated. The results show copper ions (0–100 μM) have little influence on the secretion of macrophage-derived exosomes. Endothelial cells can uptake the exosomes from all the groups in a time-dependent manner. The exosomes have little influence on endothelial adhesion and proliferation, but can upregulate angiogenic ability of endothelial cells in vitro and in vivo, which may be related to trafficking of integrin β1. The results provide insight into the effect of copper ions on immunomodulatory mechanism of macrophages, which is important for implant design from the perspective of material compositions.

铜是植入物材料的常用添加剂，它可以改变巨噬细胞表型，从而决定植入物的命运。哺乳动物细胞分泌的外来体可以靶向受体细胞并介导其功能。然而，尚不清楚在铜离子刺激下源自巨噬细胞的外泌体是否可以调节血管生成，这是植入物骨整合的关键指标。在其中，研究了铜离子对巨噬细胞来源的外泌体分泌，内皮细胞的摄取行为以及血管生成诱导能力的影响。结果表明，铜离子（0-100μM）对巨噬细胞来源的外泌体的分泌影响很小。内皮细胞可以以时间依赖的方式摄取所有组的外来体。外泌体对内皮细胞的黏附和增殖影响很小，在体外和体内，这可能与整联蛋白β1的运输有关。结果提供了洞察铜离子对巨噬细胞免疫调节机制的影响，这从材料组成的角度对于植入物设计很重要。