Division for Health Service Promotion, the University of Tokyo.
Department of Cardiovascular Medicine, the University of Tokyo.
J Atheroscler Thromb. 2020 Dec 1;27(12):1299-1309. doi: 10.5551/jat.52720. Epub 2020 Feb 26.
Synthetic vascular grafts are widely used in surgical revascularization, mainly for medium- to large-sized vessels. However, synthetic grafts smaller than 6 mm in diameter are associated with a high incidence of thrombosis. In this study, we evaluated silk fibroin, a major protein of silk, with high biocompatibility and biodegradability, as a useful material for extremely-small-diameter vascular grafts.
A small-sized (0.9 mm inner diameter) graft was braided from a silk fibroin thread. The right carotid arteries of 8- to 14-week-old male C57BL/6 mice were cut at the midpoint, and fibroin grafts (5- to 7-mm in length) were transplanted using a cuff technique with polyimide cuffs. The grafts were harvested at different time points and analyzed histologically.
CD31+ endothelial cells had already started to proliferate at 2 weeks after implantation. At 4 weeks, neointima had formed with α-smooth muscle actin+ cells, and the luminal surface was covered with CD31+endothelial cells. Mac3+ macrophages were accumulated in the grafts. Graft patency was confirmed at up to 6 months after implantation.
This mouse model of arterial graft implantation enables us to analyze the remodeling process and biocompatibility of extremely-small-diameter vascular grafts. Biodegradable silk fibroin might be applicable for further researches using genetically modified mice.
合成血管移植物广泛应用于外科血运重建,主要用于中到大血管。然而,直径小于 6 毫米的合成移植物与高血栓发生率相关。在本研究中,我们评估了丝素蛋白,一种具有高生物相容性和可生物降解性的丝主要蛋白质,作为极细直径血管移植物的有用材料。
用丝素蛋白线编织小直径(内径 0.9 毫米)移植物。将 8 至 14 周龄雄性 C57BL/6 小鼠的右颈动脉在中点切开,并用聚酰亚胺套管的袖套技术移植丝素移植物(5 至 7 毫米长)。在不同时间点收获移植物并进行组织学分析。
植入后 2 周,CD31+内皮细胞已开始增殖。4 周时,有 α-平滑肌肌动蛋白+细胞形成新生内膜,管腔表面覆盖有 CD31+内皮细胞。Mac3+巨噬细胞在移植物中聚集。植入后 6 个月确认移植物通畅。
这种动脉移植物植入的小鼠模型使我们能够分析极细直径血管移植物的重塑过程和生物相容性。可生物降解的丝素蛋白可能适用于进一步使用基因修饰小鼠的研究。