Host recognition and immune-mediated foreign body response to biomaterials can compromise the performance of implanted medical devices. To identify key cell and cytokine targets, here we perform in-depth systems analysis of innate and adaptive immune system responses to implanted biomaterials in rodents and non-human primates. While macrophages are indispensable to the fibrotic cascade, surprisingly neutrophils and complement are not. Macrophages, via CXCL13, lead to downstream B cell recruitment, which further potentiated fibrosis, as confirmed by B cell knockout and CXCL13 neutralization. Interestingly, colony stimulating factor-1 receptor (CSF1R) is significantly increased following implantation of multiple biomaterial classes: ceramic, polymer and hydrogel. Its inhibition, like macrophage depletion, leads to complete loss of fibrosis, but spares other macrophage functions such as wound healing, reactive oxygen species production and phagocytosis. Our results indicate that targeting CSF1R may allow for a more selective method of fibrosis inhibition, and improve biomaterial biocompatibility without the need for broad immunosuppression.

中文翻译：

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集落刺激因子-1受体是异物对啮齿动物和非人类灵长类动物中生物材料植入物反应的重要组成部分

宿主识别和免疫介导的异物对生物材料的反应可能会损害植入医疗设备的性能。为了确定关键的细胞和细胞因子靶标，我们在这里对啮齿动物和非人类灵长类动物对植入的生物材料的先天性和适应性免疫系统反应进行了深入的系统分析。虽然巨噬细胞对于纤维化级联反应是必不可少的，但令人惊讶的是嗜中性粒细胞和补体却不是。巨噬细胞通过CXCL13导致下游B细胞募集，这进一步增强了纤维化，如B细胞敲除和CXCL13中和所证实。有趣的是，在植入多种生物材料类别（陶瓷，聚合物和水凝胶）后，集落刺激因子1受体（CSF1R）显着增加。像巨噬细胞耗竭一样，它的抑制作用会导致纤维化完全消失，但保留了其他巨噬细胞功能，例如伤口愈合，活性氧产生和吞噬作用。我们的结果表明，靶向CSF1R可能允许采用更具选择性的纤维化抑制方法，并无需广泛的免疫抑制即可改善生物材料的生物相容性。