High-Purity Magnesium Staples Suppress Inflammatory Response in Rectal Anastomoses

Magnesium-based materials are promising biodegradable implants, although the impact of magnesium on rectal anastomotic inflammation is poorly understood. Thus, we investigated the inflammatory effects of high-purity Mg staples in rectal anastomoses by in vivo luciferase reporter gene expression in transgenic mice, hematoxylin-eosin staining, immunohistochemistry, and Western blotting. As expected, strong IL-1β-mediated inflammation and inflammatory cell infiltration were observed 1 day after rectal anastomoses were stapled with high-purity Mg or Ti. However, inflammation and inflammatory cell infiltration decreased more robustly 4-7 days postoperation in tissues stapled with high-purity Mg. This rapid reduction in inflammation was confirmed by immunohistochemical analysis of IL-6 and TNF-α. Western blot also suggested that the reduced inflammatory response is due to suppressed TLR4/NF-κB signaling. In contrast, MCP-1, uPAR, and VEGF were abundantly expressed, in line with the notion that expression of these proteins is regulated by feedback between the VEGF and NF-κB pathways. In vitro expression of MCP-1, uPAR, and VEGF was also similarly high in primary rectal mucosal epithelial cells exposed to extracts from Mg staples, as measured by antibody array. Collectively, the results suggest that high-purity Mg staples suppress the inflammatory response during rectal anastomoses via TLR4/NF-κB and VEGF signaling.