Arterial Remodeling in Cell-free, Fast-degrading Vascular grafts using a Rat Carotid Artery Interposition Model

The clinical need for vascular grafts is increasing with the increasing incidence of cardiovascular diseases. Autologous grafts have limited availability and cause donor site morbidity. We have developed cell-free,... [ view full abstract ]

The clinical need for vascular grafts is increasing with the increasing incidence of cardiovascular diseases. Autologous grafts have limited availability and cause donor site morbidity. We have developed cell-free, biodegradable vascular grafts, which have demonstrated accelerated cell infiltration and host remodeling in a rat abdominal aorta model. However, the grafts needed urgently in the clinic are for small arteries. Here, we assessed the host remodeling of our grafts using a rat carotid artery interposition model. Compared to the abdominal aorta, the common carotid artery is smaller in diameter, has lower flow rate, and is more muscular, matching the clinical need for small arterial grafts. We fabricated bi-layered composite grafts: with a fast-degrading elastomer, poly(glycerol sebacate) core and an electrospun polycaprolactone outer sheath (Fig. 1A). We implanted these grafts into the rat common carotid artery by end-to-end anastomosis (Fig. 1B). We checked graft patency with ultrasound scanning at 2, 4, 8, 12-week post-implantation. We explanted grafts at 12-week post-implantation, and assessed host remodeling using histology, immunofluorescence staining, and biaxial inflation testing. Ultrasound scanning confirmed the graft patency, demonstrating no thrombosis and aneurysm formation (Fig. 1B). Histology and immunofluorescence staining demonstrated endothelial monolayer in lumen and organized smooth muscle cells in medial layer (Figs. 1C and 1D). Mechanical testing showed that the neoartery had higher circumferential modulus than a native carotid artery. Our results confirmed successful neoartery remodeling in the cell-free, fast-degrading vascular grafts following rat carotid artery interposition. Our vascular grafts can be ideally suited for small-diameter arterial regeneration.