A Biomimetic Approach To Developing Antithrombotic Small-Caliber Prosthetic Vascular Grafts

Introduction: Prosthetic grafts smaller than 6 mm in diameter are linked with a high incidence of thrombosis and neointimal hyperplasia. We developed a novel graft material that provides controlled release of nitric oxide (NO), an antithrombotic agent that also promotes endothelialization within the lumen. Our very recent study focused on NO release kinetics from a similar composite that demonstrated controlled NO release for up to 200 d with a total release of 1.03 ± 0.09 μmol/mg. Methods: Grafts were fabricated using an electrospinning process that yields a micro-fibrous web composed of poly(ε-caprolactone) (PCL) . These fibers were doped with NO donor diethylenetriamine diazeniumdiolate (DETA/NO) and embedded within a polydimetheylsiloxane (PDMS) elastomer, which was found to regulate water transport and NO release rate. In vitro studies were tested in PBS at 37 C using a Griess assay to compute NO release. The shape memory properties inherent to this composite were used to form kink resistant acute angles through exposure to specific thermal cycles under strain. Results: NO release was proportional to DETA/NO doping and regulated by PDMS. Our present study revealed that the critical radius of curvature, below which kinks form, is a function of graft wall thickness and that a radii of curvature as small as 6 mm can be achieved using our unique process. The accompanying figure shows a 4 mm diameter graft with 0.8 mm wall thickness formed into a kink-free form with a radius of curvature of 6.7 mm. Conclusions: Incorporation of DETA/NO into a PCL/PDMS composite offers tunable long-term NO release and is a candidate for kink-resistant vascular grafts.