Combining collagen, an established regenerative biomaterial, and copper (Cu) with its known antibacterial and angiogenic effects could improve wound healing. However, Cu is also cytotoxic. Thus, this study aimed at examining the tissue reactions after simultaneous intramuscular implantation of collagen discs either without Cu (controls) or impregnated in 2, 20, or 200 mmol/L Cu acetate in 24 rats. After 7, 14, and 56 days, implants with peri‐implant tissue were retrieved from 8 rats/day for immunohistochemical detection of CD68⁺ monocytes/macrophages and CD163⁺ macrophages, MHC‐II⁺ cells, T lymphocytes and nestin as tissue regeneration marker. CD68⁺ monocytes/macrophages around implants increased with Cu amount but decreased over time except for the highest Cu amount, while CD163⁺ macrophages increased over time around and within implants. MHC‐II⁺ cells were similar to CD68⁺ monocytes/macrophages. T lymphocyte numbers around implants were higher for Cu‐impregnated samples vs. controls on day 7 and highest on day 14, but declined afterwards. Nestin expression around and within implants was largely unaffected by Cu. In conclusion, pro‐inflammatory reactions around implants were dose‐dependently influenced by Cu but mostly decreased over time, while Cu did not negatively affect anti‐inflammatory and regenerative reactions. These results suggest that Cu‐impregnated collagen could be beneficial in wound treatment.

中文翻译：

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铜浸渍胶原植入物对大鼠植入后局部促炎和抗炎以及再生组织反应的影响。

将胶原蛋白（一种成熟的再生生物材料）与具有已知抗菌和血管生成作用的铜 (Cu) 相结合，可以改善伤口愈合。然而，Cu 也是细胞毒性的。因此，本研究旨在检查在 24 只大鼠中同时肌肉内植入不含铜（对照）或浸渍 2、20 或 200 mmol/L 醋酸铜的胶原椎间盘后的组织反应。7、14 和 56 天后，每天从 8 只大鼠中取出带有种植体周围组织的种植体，用于免疫组织化学检测 CD68 ⁺单核细胞/巨噬细胞和 CD163 ⁺巨噬细胞、MHC-II ⁺细胞、T 淋巴细胞和巢蛋白作为组织再生标志物. CD68 ⁺植入物周围的单核细胞/巨噬细胞随着铜量的增加而增加，但随着时间的推移而减少，除了最高的铜量，而 CD163 ⁺巨噬细胞随着时间的推移而增加。MHC-II ⁺细胞与 CD68 ⁺相似单核细胞/巨噬细胞。与对照组相比，Cu 浸渍样品在植入物周围的 T 淋巴细胞数量在第 7 天较高，在第 14 天最高，但随后下降。植入物周围和内部的巢蛋白表达在很大程度上不受 Cu 的影响。总之，植入物周围的促炎反应受 Cu 呈剂量依赖性影响，但随着时间的推移大多减少，而 Cu 不会对抗炎和再生反应产生负面影响。这些结果表明，Cu 浸渍的胶原蛋白可能有益于伤口治疗。