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

Abstract

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 dosedependently 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.

Quantitative analysis of trabecular bone tissue cryosections via a fully automated neural network-based approach

“…HE staining was performed according to standard protocols [ 23 , 24 ]. Sections were fixated in ice-cold acetone and dried for at least 30 minutes at 37°C.…”

Collagen-Based Biomaterials for Tissue Engineering

“…Low-concentration copper-impregnated collagen may cause chronic tissue damage after 56 days of implantation in rats but increase the M2-like macrophage response, which indicates a healing tendency acting like a chemical debridement approach. However, the blood concentration of heavy metal ions and systemic toxicity is still a large problem that needs to be taken into consideration and fully assessed . A praseodymium–cobaltite reinforced collagen sheet has shown effects on angiogenesis and promoting differentiation of MSCs into endothelial cells, and better wound healing compared to native collagen, indicating that rare-earth elements may have potential in producing biomaterials for tissue engineering.…”

“…However, the blood concentration of heavy metal ions and systemic toxicity is still a large problem that needs to be taken into consideration and fully assessed. 33 A praseodymium−cobaltite reinforced collagen sheet has shown effects on angiogenesis and promoting differentiation of MSCs into endothelial cells, and better wound healing compared to native collagen, 34 indicating that rare-earth elements may have potential in producing biomaterials for tissue engineering. Moreover, collagen in combination with inorganic materials has been utilized for enhanced tissue regeneration recently.…”

A convenient approach by using poly‐(HEMA‐co‐NIPAM)/Cu2+ solution sol–gel transition for wound protection and healing

“…Although a series of antibacterial agents have been developed against biofilm formation, they are often accompanied by undesired side effects (Halbus, Horozov, & Paunov, 2019;Wang et al, 2019). Specifically, copper ions (Cu 2+ ) exhibit excellent antibacterial properties (Hoene et al, 2020;Xu, Shi, Lei, & Dai, 2020).…”

“…Although a series of antibacterial agents have been developed against biofilm formation, they are often accompanied by undesired side effects (Halbus, Horozov, & Paunov, 2019; Wang et al, 2019). Specifically, copper ions (Cu 2+ ) exhibit excellent antibacterial properties (Hoene et al, 2020; Xu, Shi, Lei, & Dai, 2020). Moreover, Cu 2+ has been found to play a crucial role in promoting breast tumor angiogenesis (Bharathi Devi, Dhivya, & Sulochana, 2016; Lopez, Ramchandani, & Vahdat, 2019), which has become a significant factor for tissue engineering.…”