Improvement of a Novel Small-diameter Tissue-engineered Arterial Graft With Heparin Conjugation

Abstract

Small diameter (<6 mm), bioabsorbable, arterial, tissue-engineered vascular grafts (TEVGs) remain limited by thromboembolism. The objective of this study was to test whether heparin-eluting (HE) TEVGs prevent early thrombosis in a large animal model. TEVGs were created with an outer poly-ε-caprolactone electrospun nanofiber layer, with a 15-μm average pore size and an inner layer composed of a 50:50 poly(L-lactide-co-ε-caprolactone) copolymer. Adult female sheep (n= 5) underwent bilateral carotid artery interposition grafting, with a control TEVG in 1 carotid artery and an HE TEVG in the contralateral position. Animals were followed for 8 weeks with weekly Duplex ultrasonography to monitor TEVG performance. All sheep survived to the designated endpoint. At 8 weeks all 5 HE TEVGs were patent. Three of 5 control TEVGs had early thrombotic occlusion at <1 week. More than 97% of heparin release occurred within the first 24 hours. Histologic evaluation of the HE TEVG displayed cellularity like a native carotid artery with no evidence of calcification. Significantly fewer platelets adhered to the HE TEVG than to the control TEVG (P < .001). This study suggests HE TEVGs prevent acute graft thrombosis. We hypothesize that the HE properties of the HE TEVG during vascular endothelialization is useful for maintaining TEVG patency. This technique may aid in the translation of small arterial TEVGs to the clinic.