Exploring the structure-processing-property relationships of Poly(l-lactic acid) in bioresorbable vascular scaffolds using high resolution characterisation

Abstract

Coronary heart disease (CHD) is the leading cause of death globally, caused by plaque build-up in the coronary arteries. It is typically treated with metallic drug-eluting stents to clear blockages and restore blood flow. However, long-term issues with stents have led to the development of bioresorbable vascular scaffolds (BVS). BVS are designed to temporarily support the artery and then dissolve, leaving behind a healthy vessel.

Poly(l-lactic acid) (PLLA) is biodegradable and biocompatible and is the structural polymer used in the first clinically approved BVS. However, PLLA-based BVS need to be thicker than metallic stents to provide similar support, which can complicate their implantation and increase the risk of further blockages. Research is ongoing to optimise the manufacturing and performance of BVS, focusing on improving their mechanical properties and reducing thickness. Medical-grade PLLA material, produced under stringent quality control measures to ensure no impurities and characterised by a high molecular weight, is associated with a significant cost. Consequently, research groups may consider using more economical packaging-grade PLLA as an alternative. However, the validity of this substitution has not been thoroughly tested. The first study in this thesis employs characterisation techniques to demonstrate that packaging-grade PLLA is a viable and cost-effective alternative to medical-grade for early-stage research applications, particularly due to its comparable mechanical properties following biaxial stretching.

Digital image correlation (DIC) is an optical method used to measure full-field displacements and strains on material surfaces during mechanical testing. This work used microscopic DIC to specifically examine the "U-bends" --- the small regions of a scaffold where the curvature is highest and stress is maximised during crimping, potentially leading to device failure with dramatic consequences on patient life. A custom-made crimping rig, specifically designed to test idealised U-bend samples, allows the acquisition of strain and deformation characteristics during the crimping and expansion processes with a known thermal and strain history. By visualising strain in-situ, DIC provides detailed insights, essential for optimising the design and ensuring the mechanical integrity of BVS. This study demonstrates that DIC can offer high-resolution data on the strain evolution of these small samples, aiding in the development of accurate material models and improving BVS performance. The DIC analysis showed consistently higher strain at the inner bend relative to the outer bend during both crimping and expansion, identifying critical regions for failure risk and providing valuable input for computational modelling.
Crystal structure and morphology dictate the mechanical, thermal, and degradation properties of PLLA. In the final study, experimental methods were developed to reveal the underlying mechanisms governing structure formation during the crimping step of the BVS manufacturing process and the expansion step of the clinical deployment process. Modifications to the crimping rig, to operate at a synchrotron, enabled the collection of wide- and small-angle X-ray scattering to probe local variations of the morphology as a function of position in the crest of the U-bends. Spatially-resolved measurements at 5 µm resolution showed that variations in crystalline morphology are strongly influenced by the initial biaxial stretch and processing history. Additionally, polarised light microscopy (PLM) images supported these findings, highlighting stress distributions across the deformed U-bends linked to earlier stretch conditions. The integrated X-ray scattering-microscopy approach offered a comprehensive workflow for uncovering the intricate relationship between processing conditions and the corresponding spatially-resolved semicrystalline morphology of a BVS.

Each study within this work adds key insights to the physical and mechanical behaviour of PLLA and its potential for use as a bioresorbable vascular scaffold material. The findings on packaging vs medical-grade PLLA highlight potential cost reductions and accelerated development for research. Offering higher resolution and deeper insights into strain and deformation characteristics than existing methods, the DIC study provides insights into strain evolution during crimping and expansion that can aid in the validation of computational models. The X-ray work represents the first opportunity to investigate microstructure changes immediately after crimping, providing enhanced control over each processing step. These advancements can significantly improve designing scaffolds that better withstand deployment and physiological conditions.

Thesis is embargoed until 31 July 2027.

Date of Award	Jul 2025
Original language	English
Awarding Institution	Queen's University Belfast
Supervisor	Alex Lennon (Supervisor) & Gary Menary (Supervisor)