Porous electrospun poly(glycerol sebacate)-based vascular grafts demonstrate early cell infiltration in a porcine arteriovenous shunt model

In situ tissue engineering of vascular grafts circumvents many obstacles to translation faced by cell-seeded designs. However, to achieve complete remodeling, cell-free scaffolds must support extensive host cell infiltration... [ view full abstract ]

In situ tissue engineering of vascular grafts circumvents many obstacles to translation faced by cell-seeded designs. However, to achieve complete remodeling, cell-free scaffolds must support extensive host cell infiltration via high porosity and pore size. Porous vascular graft cores were electrospun from a blend of poly(glycerol sebacate) PGS prepolymer and polyvinyl alcohol (PVA). After crosslinking, the cores were washed to remove mobile PVA. The cores were reinforced with an electrospun wrap of polycaprolactone (PCL) and a nonporous synthetic sealant layer. PGS/PVA cores had a dry porosity of 71±3% and a PVA content of 9.7±0.7% wt. PGS/PVA fiber diameter was 3.29±2.79 μm. Reinforcement improved the circumferential incremental modulus from 127±37 to 1920±170 kPa, the ultimate tensile strength from 588±134 to 1290±80 kPa, and the suture retention load from 45±7 gf to 279±40 gf. Furthermore, grafts demonstrated more complete and rapid closure after needle puncture than did standard ePTFE grafts, which could allow cannulation of the graft soon after implantation and reduce workflow delays during implant and dialysis procedures. Composite grafts were implanted in pigs as carotid arteriovenous shunts. The animals were maintained on aspirin. At 15 d, H&E staining indicated cell infiltration and ECM deposition proceeding radially outwards from the lumen through approximately 2/3 of the wall. Possible endothelial, intimal, and medial layers were observed. Putative endothelial cells expressed CD31. Ongoing studies will assess the degradation/remodeling timelines in vitro and in vivo, quantify patency, evaluate infiltrating cell phenotypes, and assess neotissue quality.