Engineering compliant, small diameter vascular prosthesis for bypass graftingdissertation
Аннотация: 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 Abstract ii 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 interstrut 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.iii Lay Summary v Lay SummaryCardiovascular diseases (CVDs) remain a major cause of death worldwide, accounting for millions of deaths.The most common forms of CVDs are heart attacks and strokes; both are attributed to the pathogenesis of atherosclerosis, which is a continuous plaque build-up that leads into a narrowing of the inner diameter of the artery and eventually to thrombosis.Diseased sites frequently require replacement with synthetic blood vessels, in order to restore the blood flow.With expanded polytetrafluoroethylene and polyethylene terephthalate, there exist clinical solutions for the substitution of diseased arterial tissue.However, for small diameter artery (< 6 mm) replacement, both materials suffer blockage after a couple of months.This is attributed to a mechanical mismatch, i.e. a mismatch in radial expansion between the grafted artery and the synthetic vascular prosthesis (compliance mismatch).Therefore, an arterial substitute with matched compliance is required, in order to minimize the incidences of post-implantation blockages.However, up to this day, this presents an elusive task to researchers, as arterial tissue exhibits idiosyncratic elastic properties: at low blood pressure arteries are highly compliant (elastic) and become increasingly stiff when the pressure is raised.In this work, the aim was to fabricate a prosthesis with arterial-like compliance.In an initial set of experiments, different materials were tested to fabricate vascular grafts of 4 mm inner diameter via dip-coating.Poly-L-lactide-co-ε-caprolactone (PLC) polymers of different monomer ratios (L-lactide (LA) to ε-caprolactone (CL)) were used for tube fabrication and assessed on their mechanical properties.PLC polymers of roughly equal monomer feeds were more elastic, due to their predominantly amorphous microstructure.Conversely, predominantly LA-or CL-rich PLC polymers were stiff because of their high crystalline phase content.PLC 50:50 (50% LA and 50% CL) and 70:30 were suitable materials for the fabrication tubular grafts with high compliance in the range of arterial tissue.However, PLC 50:50 was found to be too weak and therefore PLC 70:30 was favored as tube material.The compliance of PLC 70:30 tubes could be tailored by the wall-thickness (WT), which revealed thinner tubes were more elastic than thicker ones.PLC 70:30 tubes of 150 µm WT showed compliance in the range of porcine arteries (81% relative to the porcine artery, 100%).A three-hour animal test in a rabbit showed 150 µm WT PLC 70:30 tubes remained mechanically stable and free of any defects such as needle tears, aneurysmal dilatation or wall rupture. Lay Summary viIn order to produce vascular substitutes with non-linear elasticity, bi-layered dip-coated tubes of a soft inner lining and a stiffer outer layer were fabricated.None of these tubes showed arterial-like elastic properties.However, in principle the approach of a composite structure of a soft and stiff material to mimic the elastic properties of arteries was found to be favorable, but not by fabricating a bi-layered tube.Therefore, a different structure had to be considered and hence the winding of melt-spun fibers around a soft dip-coated tube was considered.Different parameters were tested, such as tube and fiber material combination, spinning speed and circumferential or helical fiber winding.The winding of stiffer material fibers around dip-coated tubes reduced the compliance, as did increased spinning speeds.The latter was due to stress-induced crystallization, which occurs with faster fiber winding.Slow spun PLC 70:30 fibers (at 100 rotations per minute) around a PLC 70:30 tube produced non-linear elastic prostheses.It is assumed the slow spinning may have led to fiber shrinkage and coiling of the polymer chains that first require unfolding, before they get stretched.Another approach using a more deliberate composite structure of a 3D-bioprinted pliable stiffer outer mesh was considered, in order to obtain a non-linear elastic prosthesis.Single fiber tensile tests were carried out to verify, whether such pliable fibers could produce such a behavior.Four spring types, zig-zag (ZZ), semi-hexagonal (HEX), stair (ST) and sine-wave (S) were considered, and all provided easy fiber unfolding at low strains.Upon complete fiber straightening, the fiber material itself got stretched, which created a transition from low to high stiffness.This could be seen from a J-shaped Curve (J-Curve) in the stress-strain diagrams.Several geometrical designs were tested before meshes comprising such spring-like fibers, J-Curve Meshes (J-Meshes), were printed.Afterwards, composites of a soft dip-coated tube with an outer J-Mesh (JM-Tubes) were fabricated and evaluated on their mechanical properties during dynamic compliance tests.Combining a thin (~55µm WT) PLC 70:30 tube and dense HEX-mesh with two hoops (springs) per round, made of PCL or PLC 95:5, produced JM-Tubes with non-linear elastic properties.A clear transition from high to low compliance was observed for such JM-Tubes.This proves the viability of the JM-Tubes, but yet requires optimization in further work, in order to better match the compliance profile of native arteries.
Год издания: 2018
Авторы: Jean‐Marc Behr
Ключевые слова: Electrospun Nanofibers in Biomedical Applications, Cardiac and Coronary Surgery Techniques, Tissue Engineering and Regenerative Medicine
Открытый доступ: hybrid