Engineering compliant, small diameter vascular prosthesis for bypass grafting

Mechanical mismatch between vascular grafts and blood vessels is a major cause of smaller diameter graft (< 6 mm) failure. The fabrication of a compliant small diameter prosthesis remains elusive, due to the idiosyncratic elastic properties of arterial wall tissue. Native blood vessels exhibit a pressure-dependent compliance (non-linear elasticity), which is a principal reason behind the decade-long search for a clinical solution for small diameter vessel replacement. Mimicking the non-linear elastic properties of arterial tissue is the major goal in this thesis and has been achieved over multiple steps. Initial research involved the evaluation of several poly-L-lactide-co-ε-caprolactone (PLC) copolymers as candidate materials for the fabrication of small diameter grafts. Using these materials, tubular prostheses of 4 mm inner diameter were produced by dip-coating. In vitro static and dynamic compliance tests were conducted, using a custom-built apparatus. Mechanical testing revealed a compliance-dependence on the monomer composition and the wall-thickness (WT) of the PLC tubes. PLC 70:30 tubes of 150 μm WT were similarly compliant as the porcine arteries. These tubes were assessed in a three hours in vivo experiment in a lupine model as an aortic bypass on their implantation and function. The recorded angiogram showed continuous blood flow, no aneurysmal dilatation, leaks or acute thrombosis, indicating the potential for clinical applications. In order to achieve non-linear elasticity, different approaches were pursued, such as adding a soft inner lining to a PLC tube or outer melt-drawn fibers. However, none of these methods produced satisfying results. Hence, a third strategy was followed up, by combining a soft dip-coated tube with a 3D-printed outer pliable mesh. In an initial test, single spring-like fibers were assessed on their tensile properties. All fibers showed clear signs of non-linear elasticity, displaying an increasing elastic modulus upon unfolding in the stress-strain diagrams (J-Curve). Among the all tested spring geometries, the semi-hexagonal (HEX) were the most satisfying. Based on the results from the tensile experiments, meshes of different designs were printed and wrapped around a soft dip-coated PLC 70:30 tube to form a mesh-tube composite (JM-Tube). Initially, the dip-coated tube was not elastic enough to sufficiently unfold the mesh and moreover expanded between the mesh struts. Fiber unfolding was facilitated when using HEX-meshes with two spring sections that were separated by a middle glue strip. This configuration allowed a better stress transfer from the tube to the fiber to enable easier unfolding. A reduction of the WT of the PLC 70:30 tube from ~100 μm to ~55 μm made the tube sufficiently elastic so that it could expand easily to force the mesh fibers to unfold. The use of meshes with high fiber coverage minimized tubular inter-strut expansion. By combining these three advances, the JM-Tubes then displayed the desired non-linear elastic properties. This work demonstrates arterial-like compliance properties can be achieved by combining a soft dip-coated tube with a pliable stiffer outer mesh. Further optimizations in the design are required, to improve the compliance matching to native arteries.Doctor of Philosoph