Abstract

Background: There is an increasing need for vascular grafts in the field of surgical revascularization. However, smaller vascular grafts made from synthetic biomaterials, particularly smaller than 5 mm in diameter, are associated with high incidence of thrombosis. Fibroin is a biodegradable protein derived from silk. Fibroin provides anti-thrombotic surface and serves as a scaffold for various cell types in tissue-engineering. In this study, we evaluate the potential of fibroin to generate artificial vascular prosthesis for small arteries. Methods and Results: A small artificial vessel with three layers was woven from fibroin thread. Fibroin-based grafts (1.5 mm in diameter, 10 mm in length) were implanted into the abdominal aorta of male 10 to 14-week-old Sprague Dawley rats by end-to-end anastomosis. Polytetrafluoroethylene (PTFE)-based grafts were used as control. Patency of fibroin grafts at 1 year after implantation was significantly higher than that of PTFE grafts (85.1% vs. 30%, p<0.01). Endothelial cells and smooth muscle cells migrated into the fibroin graft early after implantation and organized endothelial and medial layers, as determined by anti-CD31 or anti-α-smooth muscle actin immunostaining. Vasa vasorum was also formed in adventitia. Sirius-red staining revealed that the content of collagen in fibroin grafts significantly increased at 3 months after implantation (1613.5 ± 246.3%, p<0.01) with decrease in fibroin fiber content (70.6 ± 4.6%, p<0.05). To investigate the origin of the cells of neointima and media, we performed bone marrow transplantation from GFP rats to wild-type rats. GFP-positive cells substantially contributed to organization of endothelium and smooth muscle layers in the fibroin grafts that had been implanted into the bone marrow chimeric rats. Conclusion: A small-diameter fibroin-based vascular graft has significantly higher patency than a PTFE-based graft. Bone marrow-derived cells contribute to vascular remodeling after graft implantation. Fibroin might be a promising material to engineer vascular prosthesis for small arteries.

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