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For gastrointestinal anastomosis, metallic biodegradable staples have a broad application potential. However, both magnesium and zinc alloys have relatively low strength to withstand the repeated peristalsis of the gastrointestinal tract. In this study, we developed a novel kind of biodegradable high-nitrogen iron (HN-Fe) alloy wires (0.23 mm), which were fabricated into the staples. The tensile results showed that the ultimate tensile strength and elongation of HN-Fe wires were 1023.2 MPa and 51.0%, respectively, which was much higher than those of other biodegradable wires. The degradation rate in vitro of HN-Fe wires was slightly higher than that of pure Fe wires. After 28 days of immersion, the tensile strength of HN-Fe wires remained not less than 240 MPa, meeting the clinical requirements. Furthermore, sixteen rabbits were enrolled to conduct a comparison experiment using HN-Fe and clinical Ti staples for gastroanastomosis. After 6 months of implantation, a homogeneous degradation product layer on HN-Fe staples was observed and no fracture occurred. The degradation rate of HN-Fe staples in vivo was significantly higher than that in vitro, and they were expected to be completely degraded in 2 years. Meanwhile, both benign cutting and closure performance of HN-Fe staples ensured that all the animals did not experience hemorrhage and anastomotic fistula during the observation. The anastomosis site healed without histopathological change, inflammatory reaction and abnormal blood routine and biochemistry, demonstrating good biocompatibility of HN-Fe staples. Thereby, the favorable performance makes the HN-Fe staples developed in this work a promising candidate for gastrointestinal anastomosis.

In-stent restenosis can be caused by the activation, proliferation and migration of vascular smooth muscle cells (VSMCs), which affects long-term efficacy of interventional therapy. Copper (Cu) has been proved to accelerate the endothelialization and reduce thrombosis formation, but little is known about its inhibition effect on the excessive proliferation of VSMCs. In this study, 316L-Cu stainless steel and L605-Cu cobalt-based alloy with varying Cu content were fabricated and their effects on surface property, blood compatibility and VSMCs were studied in vitroand in vivo. CCK-8 assay and EdU assay indicated that the Cu-bearing metals had obvious inhibitory effect on proliferation of VSMCs. Blood clotting and hemolysis tests showed that the Cu-bearing metals had good blood compatibility. The inhibition effect of the Cu-bearing metals on migration of cells was detected by Transwell assay. Further studies showed that Cu-bearing metals significantly decreased the mRNA expressions of bFGF, PDGF-B, HGF, Nrf2, GCLC,GCLM,NQO1andHO1. The phosphorylation of AKT and Nrf2 protein expressions in VSMCs were significantly decreased by Cu-bearing metals. Furthermore, it was also found that SC79 and TBHQ treatments could recover the protein expressions of phospho-AKT and Nrf2, and their downstream proteins as well. Moreover, 316L-Cu stent proved its inhibitory action on the proliferation of VSMCs in vivo. In sum, the results demonstrated that the Cu-bearing metals possessed apparent inhibitory effect on proliferation and migration of VSMCs via regulating the AKT/Nrf2/ARE pathway, showing the Cu-bearing metals as promising stent materials for long-term efficacy of implantation.