Effects of copper-impregnated collagen implants on local pro- and anti-inflammatory and regenerative tissue reactions following implantation in rats.

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 200mmol/L Cu acetate in 24 rats. After 7, 14, and 56days, 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.