IPC02. Silk Fibroin Vascular Graft: From Design to In Vitro and In Vivo Test

A biomaterial scaffold simulating the three-layered structure of native blood vessels has been proven to be an effective way to mimic the native architecture, the mechanical behavior, and functional features of native arteries. In this study, production and characterization of an innovative multilayered silk fibroin vascular graft (SF-VG) is reported. The aim of our paper was to demonstrate the in vitro cell interaction studies performed to investigate the biological response to the device and in vivo preliminary pilot trials on animals. The SF-VG was manufactured according to a patented technology (WO 2016/067189 A1). Adult human coronary artery endothelial cells, human aortic smooth muscle cells, and human aortic adventitial fibroblasts were used for the in vitro tests. We implanted 7- to 8-cm SF-VGs as substitutes of carotid arteries in minipigs and sheep. Four weeks later the SF-VGs were explanted and submitted to a complete histopathologic investigations. The SF-VG device was manufactured by combining electrospinning and knitting/braiding technologies. The Results of in vitro cell interaction studies demonstrated the biocompatibility of SG-VG. The high basal secretion of monocyte chemoattractant protein-1 and protein-2 was indicative of a cell proliferation capacity. Interferon gamma-induced protein 10 (known for its antifibrotic and angiostatic properties) and regulated on activation, normal T-cell expressed and secreted (known for its ability to regulate leucocyte diapedesis, angiogenesis, and some scarring processes) were expressed at significant levels. The pilot animal studies showed the feasibility of using SF-VG as vessel grafts in vivo. We set up pilot studies by replacing resected portions of the common carotid arteries of two minipigs and one sheep with SF-VGs, humanely killing the animals 4 weeks later and examining their histopathologic patterns. Our aim was to assess which animal species was better in future in-depth investigations on the behavior of the SF-VG in vivo. After this pilot study, we moved to a preliminary study on six sheep with bilateral resection of common carotid artery and replacing by SF-VGs. After 6 months, no lumen stenosis and hence a persistent good blood flow was observed in sheep. SF-VG is proposed as a new vascular graft entirely made of pure silk fibroin. In vitro cell interaction studies showed that the device favors cell adhesion and their survival and growth. Short-term in vivo studies to assess the patency and wall remodeling of SF-VGs seem to be satisfying in term of patency rate.