Negative In Vivo Results Despite Promising In Vitro Data With a Coated Compliant Electrospun Polyurethane Vascular Graft

Abstract

Introduction: There is a growing need for small-diameter (<6 mm) off-the-shelf synthetic vascular conduits for different surgical bypass procedures, with actual synthetic conduits showing unacceptable thrombosis rates. The goal of this study was to build vascular grafts with better compliance than standard synthetic conduits and with an inner layer stimulating endothelialization while remaining antithrombogenic.

Methods: Tubular vascular conduits made of a scaffold of polyurethane/polycaprolactone combined with a bioactive coating based on chondroitin sulfate (CS) were created using electrospinning and plasma polymerization. In vitro testing followed by a comparative in vivo trial in a sheep model as bilateral carotid bypasses was performed to assess the conduits' performance compared to the actual standard.

Results: In vitro, the novel small-diameter (5 mm) electrospun vascular grafts coated with chondroitin sulfate (CS) showed 10 times more compliance compared to commercial expanded polytetrafluoroethylene (ePTFE) conduits while maintaining adequate suturability, burst pressure profiles, and structural stability over time. The subsequent in vivo trial was terminated after electrospun vascular grafts coated with CS showed to be inferior compared to their expanded polytetrafluoroethylene counterparts.

Conclusions: The inability of the experimental conduits to perform well in vivo despite promising in vitro results may be related to the low porosity of the grafts and the lack of rapid endothelialization despite the presence of the CS coating. Further research is warranted to explore ways to improve electrospun polyurethane/polycaprolactone scaffold in order to make it prone to transmural endothelialization while being resistant to strenuous conditions.

Keywords: Chondroitin sulfate; Compliance; Electrospinning; In vivo study; Small-diameter vascular graft; Surface modification.