Development of a novel bio-engineered vascular bypass conduit

Abstract

This thesis summarises the deficiencies of current small-diameter synthetic conduits and the approaches to the development of an improved vascular bypass conduit. Evidence for the incorporation of elastin in the design of novel conduits is then presented. We used recombinant human tropoelastin (rhTE) to develop two novel conduits. Firstly we hypothesised that rhTE can be bound to expanded polytetrafluoroethylene (ePTFE) conduits resulting in improved biocompatibility due solely to altered surface composition. rhTE was covalently bound to 6mm-diameter ePTFE and demonstrated uniform and durable protein attachment resulting in enhanced endothelial cell attachment and proliferation. Following a modification of rhTE coating, rhTE-coated ePTFE conduits were implanted in sheep for one month and demonstrated a marked reduction in anastomotic intimal hyperplasia and equivalent patency compared to control ePTFE. In the second part of this project we hypothesised that rhTE can be used to construct an entirely novel elastic conduit (NEC) that shows biocompatibility, and demonstrates mechanical properties matching the internal mammary artery. Using electrospinning we manufactured 2-3mm diameter NECs combining rhTE and polycaprolactone and matched the compliance, burst pressure, and hydraulic permeability of the internal mammary artery. After demonstrating endothelial cell growth and low platelet attachment in vitro we implanted conduits into rabbits for 2 and 4 weeks and showed retention of mechanical properties but loss of patency due to an inflammatory response to the implanted NEC compared to control ePTFE. Several factors serve to impede the design of successful novel vascular conduits and these are discussed including difficulties in the assessment of endothelialisation and compliance, the selection of an appropriate animal model and statistical method, and problems with in vitro techniques for thrombogenicity assessment.