Prosthetic vascular grafts do not mimic the antithrombogenic properties of native blood vessels and therefore have higher rates of complications that involve thrombosis and restenosis. We developed an approach for grafting bioactive heparin, a potent anticoagulant glycosaminoglycan, to the lumen of ePTFE vascular grafts to improve their interactions with blood and vascular cells. Heparin was bound to aminated poly(1,8-octanediol-co-citrate) (POC) via its carboxyl functional groups onto POC-modified ePTFE grafts. The bioactivity and stability of the POC-immobilized heparin (POC–Heparin) were characterized via platelet adhesion and clotting assays. The effects of POC–Heparin on the adhesion, viability and phenotype of primary endothelial cells (EC), blood outgrowth endothelial cells (BOECs) obtained from endothelial progenitor cells (EPCs) isolated from human peripheral blood, and smooth muscle cells were also investigated. POC–Heparin grafts maintained bioactivity under physiologically relevant conditions in vitro for at least one month. Specifically, POC–Heparin-coated ePTFE grafts significantly reduced platelet adhesion and inhibited whole blood clotting kinetics. POC–Heparin supported EC and BOEC adhesion, viability, proliferation, NO production, and expression of endothelial cell-specific markers von Willebrand factor (vWF) and vascular endothelial-cadherin (VE-cadherin). Smooth muscle cells cultured on POC–Heparin showed increased expression of α-actin and decreased cell proliferation. This approach can be easily adapted to modify other blood contacting devices such as stents where antithrombogenicity and improved endothelialization are desirable properties.

Our nationwide network of BME women faculty collectively argue that racial funding disparity by the National Institutes of Health (NIH) remains the most insidious barrier to success of Black faculty in our profession. We thus refocus attention on this critical barrier and suggest solutions on how it can be dismantled.

One of the ongoing challenges in tissue engineering is the synthesis of a hemocompatible vascular graft. Specifically, the material used in the construct should have antithrombogenic properties and support the growth of vascular cells. Our laboratory has designed a novel biodegradable, elastomeric copolymer, poly(1,8-octanediol citrate) (POC), with mechanical and degradation properties suitable for vascular tissue engineering. The hemocompatibility of POC in vitro and its ability to support the attachment and differentiation of human aortic endothelial cell (HAEC) was assessed. The thrombogenicity and inflammatory potential of POC were assessed relative to poly(l-lactide-co-glycolide) and expanded poly(tetrafluoroethylene), as they have been used in FDA-approved devices for blood contact. Specifically, platelet aggregation and activation, protein adsorption, plasma clotting, and hemolysis were investigated. To assess the inflammatory potential of POC, the release of IL-1beta and TNF-alpha from THP-1 cells was measured. The cell compatibility of POC was assessed by confirming HAEC differentiation and attachment under flow conditions. POC exhibited decreased platelet adhesion and clotting relative to control materials. Hemolysis was negligible and protein adsorption was comparable to reference materials. IL-1beta and TNF-alpha release from THP-1 cells was comparable among all materials tested, suggesting minimal inflammatory potential. POC supported HAEC differentiation and attachment without any premodification of the surface. The results described herein are encouraging and suggest that POC is hemocompatible and an adequate candidate biomaterial for in vivo vascular tissue engineering.

A biodegradable polyester elastomer, poly(1,8‐octanediol citrate) (POC), is used to modify the lumen of expanded polytetrafluoroethylene (ePTFE) grafts via a spin‐shearing method followed by interfacial in situ polycondensation. We demonstrate successful surface modification of ePTFE grafts without affecting graft compliance (see figure). The POC interface confers hydrophilicity, reduced thrombogenicity, facilitated graft endothelialization in vitro, and reduced macrophage infiltration on the ePTFE grafts.