Abstract 6058: Fibroin, a Silk-Based Biodegradable Protein, is a Promising Material to Engineer Small-Diameter Vascular Graft

Background: Smaller vascular grafts made from synthetic biomaterials, particularly smaller than 5 mm in diameter, are associated with high incidence of thrombosis. Fibroin is a silk-derived biodegradable protein which provides anti-thrombotic surface and serves as a scaffold for various cell types in tissue-engineering. 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 (SMCs) 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 immunostain-ing, respectively. Total number of SMCs increased 1.6-fold from 1 month to 3 months after implantation. Vasa vasorum was formed in adventitia. Sirius-red staining revealed that the content of collagen in fibroin grafts significantly increased at 1 year after implantation (520.9±0.2%, p<0.05) with decrease in fibroin fiber content (32.9±1.9%, p<0.05). To investigate the origin of the cells of neointima and media, bone marrow (BM) transplantation was performed from GFP rats to wild-type rats. GFP-positive cells substantially contributed to organization of endothelium and smooth muscle layers in the fibroin grafts implanted into the BM chimeric rats. The rate of BM-derived SMCs was 70% at 1 month and 55% at 3 months after implantation. Conclusion: A small-diameter fibroin-based vascular graft has significantly higher patency than a PTFE-based graft. BM-derived cells substantially contribute to the initial formation of SMCs layer after graft implantation. The number of non-BM-derived SMCs increases at chronic phase. Fibroin might be a promising material to engineer vascular prosthesis for small arteries.