A combined experimental and computational framework to optimise processing and design of poly(L-lactic acid) bioresorbable stents

Abstract

Coronary heart disease, caused by inflammatory hardening and narrowing of arteries (atherosclerosis) is the largest cause of death in the world. Coronary stents, used to treat atherosclerosis, are typically manufactured from high strength metallic alloys; however such devices remain in the body permanently and can trigger undesirable immunological responses. Bioresorbable polymer stents offer an attractive solution, providing a temporary scaffold that resorbs once the artery heals. However, polymeric stents are mechanically inferior to their metallic counterparts, requiring thicker struts to provide equivalent radial support, which has been shown to cause elevated rates of thrombosis. This thesis aims to address the challenge of designing mechanically effective but sufficiently thin bioresorbable polymer stents through multi-objective optimisation of material parameters and stent geometry.

Initially, the processing history of a polymeric coronary stent was replicated using a custom-built biaxial tensile test machine in order to assess the improvement in short-term (pre-degradation) mechanical properties of extruded poly(L-lactic acid) (PLLA). Results of an extensive experimental programme to characterise the post­ processing material properties of PLLA indicated that biaxial deformation has the potential to enhance the elastic modulus and yield strength of extruded PLLA sheet by approximately 80% and 70%, through selection of optimal processing conditions. Both elastic modulus and yield strength were highly dependent on the aspect ratio of the biaxial deformation. Response surface methodology was used to provide empirical correlations between aspect ratio and these mechanical properties. Using these empirical correlations, a rate-independent, transversely isotropic, temperature­ dependent, elastic-plastic PLLA constitutive model was calibrated for finite element implementation.

Finally, an optimisation framework was developed that considered the combined effect of the biaxial stretching processing history and the geometric configuration when optimising the mechanical performance of a PLLA coronary stent. Forty parametric stent designs were generated by varying the aspect ratio of the biaxial deformation, along with the strut width, the strut thickness and the strut length. Each stent design was evaluated computationally, using finite element analysis, across a series of performance metrics: the cross-sectional area post-dilation, foreshortening, stent-to-artery ratio and radial collapse pressure. Pareto fronts highlighted that a change in one design parameter that improves one metric often leads to a compromise in at least one of the other metrics. Based on the results of these simulations, a set of statistical surrogate models were established that related each performance metric to the design parameters. An objective function was constructed that sought to minimise foreshortening and stent-to-artery ratio whilst maximising cross-sectional area post-dilation and radial collapse pressure. Multi­ objective optimisation was conducted using the surrogate models to produce an optimal poly(L-lactic acid) stent design that offered improved performance relative to a baseline design for the same strut thickness.

In summary, this thesis addresses key limitations in polymeric stent design and the results may be used to aid in the development of high stiffness, thin strut polymeric stents.

Date of Award	Dec 2019
Original language	English
Awarding Institution	Queen's University Belfast
Supervisor	Gary Menary (Supervisor), Alex Lennon (Supervisor) & Nicholas Dunne (Supervisor)