Aseptic loosening is a leading cause of uncemented arthroplasty failure, often accompanied by fibrotic tissue at the bone-implant interface. A biological target, neutrophil extracellular traps (NETs), was investigated as a crucial connection between the innate immune system's response to injury, fibrotic tissue development, and proper bone healing. Prevalence of NETs in peri-implant fibrotic tissue from aseptic loosening patients was assessed. A murine model of osseointegration failure was used to test the hypothesis that inhibition (through Pad4^-/- mice that display defects in peptidyl arginine deiminase 4 (PAD4), an essential protein required for NETs) or resolution (via DNase 1 treatment, an enzyme that degrades the cytotoxic DNA matrix) of NETs can prevent osseointegration failure and formation of peri-implant fibrotic tissue.

中文翻译：

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抑制 PAD4 介导的中性粒细胞胞外陷阱可防止胫骨植入小鼠模型中的纤维化骨整合失败：一项动物研究。

无菌性松动是非骨水泥关节置换失败的主要原因，通常伴有骨-植入物界面处的纤维化组织。中性粒细胞胞外陷阱 (NETs) 的生物靶标被研究为先天免疫系统对损伤的反应、纤维化组织发育和适当的骨愈合之间的关键联系。评估了无菌松动患者种植体周围纤维化组织中 NET 的患病率。使用骨整合失败的小鼠模型来检验抑制（通过Pad4 ^-/-表现出肽精氨酸脱亚胺酶 4 (PAD4) 缺陷（NET 所需的必需蛋白质）或 NET 分辨率（通过 DNase 1 处理，一种降解细胞毒性 DNA 基质的酶）缺陷的小鼠可以防止骨整合失败和种植体周围纤维化的形成组织。