Investigation of the effect of nanoparticle addition and processing history on Poly(l-lactide) stent properties

Abstract

Cardiovascular diseases (CVDs) present one of the biggest healthcare challenges in our society and remain the leading cause of death globally. Additionally, in the context of the ageing of the global population, case numbers and costs associated with CVD are expected to rise. When an artery gets blocked by plaque buildup, the common treatment is to deploy a stent to re-open the vessel and restore normal blood flow. Poly(l-lactide) bioresorbable stents (BRSs) represent a thrilling device innovation that could replace permanent metal stents currently used, leaving “nothing behind” after treatment. Despite the attractive advantage of BRS resorption, further work is needed to improve the pre-clinical stent performance.

With that aim in mind, this thesis investigates two main strategies to improve BRS mechanical properties: (i) the addition of nanoparticles (NPs) to PLLA and (ii) the refinement of the link between processing history and the PLLA microstructure and mechanical properties.

After the literature review, main criteria such as strength, compatibility with PLLA, biocompatibility and radiopacity led to the selection of tungsten disulphide inorganic nanotubes (WS₂NTs) as NPs to reinforce PLLA. The initial study corresponded to the first step of a BRS manufacturing process: the extrusion of tubes. The influence of the NPs loading and the effect of processing parameters were investigated to select the most promising tube for the next processing step. Computed tomography scans revealed that a good dispersion could be obtained at low NPs loading and under high-shear extrusion conditions. A strong nucleation effect of the WS₂NTs was evidenced but no mechanical improvements were observed at this stage, possibly due to their dramatic shortening induced during processing.

The rest of the work focused on the tube expansion process. This crucial BRS manufacturing step creates an oriented microstructure and highly improves the material strength and ductility. First, a unique setup was implemented to observe, with in-situ X-ray scattering, the interaction between WS2NTs and the PLLA microstructure forming during a radial expansion process. Results showed a poor reorientation of the nanotubes initially aligned along the extruded tube axial direction. WS₂NTs acted as nucleating agents but did not observably perturb the orientation of PLLA crystals. Second, an industrial expander was used to study the effect of expansion parameters on the scaffold microstructure and mechanical properties. Unaffected by temperature above a minimum threshold, the microstructure was, in contrast, highly sensitive to the stretch ratio applied in the axial and hoop directions during processing. The complex microstructural orientations and gradient induced were characterised and linked to the tube’s mechanical properties. Finally, PLLA/WS₂NT tubes were expanded with the industrial equipment and compared with the experimental rig. The nucleation effect of WS₂NTs, visible at low processing stretch, led to tubes with improved mechanical properties compared to neat PLLA (increase of 11 % of Young’s modulus and yield strength). However, at higher stretch ratios, the crystallisation was dominated by strain-induced crystals causing minor differences between neat and nanocomposite tubes.

In summary, this thesis uses cutting-edge characterisation techniques to investigate new material and study the effect of processing history to contribute to the development of the next generation of BRS.

Thesis is embargoed until 31 December 2024.

Date of Award	Dec 2023
Original language	English
Awarding Institution	Queen's University Belfast
Sponsors	EC/Horizon 2020 Marie Skłodowska-Curie actions
Supervisor	Alex Lennon (Supervisor), Gary Menary (Supervisor) & Brian Dillon (Supervisor)