A biodegradable synthetic graft for small arteries matches the performance of autologous vein in rat carotid arteries

Abstract

Autologous veins are the most widely used grafts for bypassing small arteries in coronary and peripheral arterial occlusive diseases. However, they have limited availability and cause donor-site morbidity. Here, we report a direct comparison of acellular biodegradable synthetic grafts and autologous veins as interposition grafts of rat carotid arteries, which is a good model for clinically relevant small arteries. Notably, extensive but transient infiltration of circulating monocytes at day 14 in synthetic grafts leads to a quickly-resolved inflammation and arterial-like tissue remodeling. The vein graft exhibits a similar inflammation phase except the prolonged presence of inflammatory monocytes. The walls of the remodeled synthetic graft contain many circumferentially aligned contractile non-proliferative smooth muscle cells (SMCs), collagen and elastin. In contrast, the walls of the vein grafts contain disorganized proliferating SMCs and thicken over time, suggesting the onset of stenosis. At 3 months, both grafts have a similar patency, extracellular matrix composition, and mechanical properties. Furthermore, synthetic grafts exhibit recruitment and re-orientation of newly synthesized collagen fibers upon mechanical loading. To our knowledge, this is the first demonstration of a biodegradable synthetic vascular graft with a performance similar to an autologous vein in small artery grafting.

Control the Mechanical Properties and Degradation of Poly(Glycerol Sebacate) by Substitution of the Hydroxyl Groups with Palmitates

“…[ 1–7 ] Of particular interest in our lab is to engineer an acellular fast‐degrading PGS vascular graft for small‐diameter arteries. [ 8–14 ] The synthetic graft is fully remodeled by host cells in months post‐implantation. The neo‐tissue possesses extracellular matrix (ECM), architecture and performance resembling to the native arteries as demonstrated in rat abdominal aorta and carotid models.…”

Strategies in cell‐free tissue‐engineered vascular grafts

“…Shinoka et al used a 50:50 poly (L-lactic-co-ε-caprolactone) (PLCL) copolymer graft as an inner layer, and two different compositions outer layer, slow-degrading PLA and fast-degrading PLA + PGA, respectively. 90.5% (19/21) PGS-PCL grafts were patent in rat carotid arteries interposition model as long as 3 months, and no statistical difference was found between the PGS-PCL grafts and the autologous external jugular vein grafts (Lee et al, 2018). The fast-degrading grafts showed greater cell infiltration in the outer layer with significantly less calcification than slow-degrading grafts, and all 10 grafts kept patent, although endothelialization and SMC proliferation were comparable (Sugiura et al, 2017).…”

“…Hemocompatibility tests showed that PGS had low platelet adhesion and inflammation, and stimulated the production of elastin (Lee et al, 2018;Motlagh, Yang, Lui, Webb, & Ameer, 2006). However, the clinical performance of synthetic grafts was poor, associated with low patency and high thrombus formation.…”

“…The in vivo performance was similar with autologous vein graft. 90.5% (19/21) PGS-PCL grafts were patent in rat carotid arteries interposition model as long as 3 months, and no statistical difference was found between the PGS-PCL grafts and the autologous external jugular vein grafts (Lee et al, 2018). Among these biodegradable polymers, PU and PGS provide good biocompatibility to allow the proliferation of ECs onto the luminal side and parietal infiltration of vascular SMCs (Rai, Tallawi, Grigore, & Boccaccini, 2012).…”

“…Strategies for surface functionalization should be an integral design aiming to eliminate thrombosis and chronic immune response and enhance ECs/EPCs adhesion. A number of researches exhibited good graft patency in small animal studies, such as mice, rats, and rabbits without anticoagulation treatments (Fukunishi et al, 2016;Kajbafzadeh et al, 2018;Lee et al, 2018;Xu et al, 2017). However, when implanted the grafts in big animals such as canines, sheep, swines, and primates, patency rates decreased remarkably due to thrombosis (Dahl et al, 2011;Fukunishi et al, 2016).…”