Thesis-2018-Naseem.pdf (12.89 MB)
Download file

Experimental study of mechanical properties and in vitro degradation of bioresorbable polymers for cardiovascular applications

Download (12.89 MB)
thesis
posted on 30.09.2021, 11:15 by Raasti Naseem
Cardiovascular disease is a prevalent group of conditions which affect a multitude of lives worldwide on a daily basis. For those individuals who require medical interventions for an occluded artery, stents are typically implanted to maintain vessel patency. Stents have developed with time from initial bare metal stents to recent drug eluting stents. The next generation of bioresorbable stents are undergoing continual research and development, particularly to battle the increased occurance of late stent thrombosis and in stent restenosis. The predominant aim of this PhD project is to assess the mechanical performance experimentally, in-vitro, of a well established, FDA approved scaffold, Absorb (Abbott Vascular, USA) composed of poly-L-lactic acid (PLLA), at a benchtop level. The work was also extended to assess the properties of novel polymers for vascular scaffold applications.

Indentation, using atomic force microscopy (AFM) and a nanoindenter with a Berkovich tip, was the predominant means adopted to assess the properties of Absorb scaffold in virgin state. This was complemented with chemical analysis of the scaffold, including gel permeation chromatography (GPC) to assess the molecular weight and differential scanning calorimetry (DSC) for crystallinity measurements, to ascertain a conclusive perspective of the material in a virgin state. Additionally optical imaging and surface profilometry measurements were taken to reveal surface properties of the scaffold. To investigate the effect of in-vitro degradation, scaffold sections were subjected to benchtop in-vitro degradation, with properties assessed using the same methodology as for the virgin samples. The effect of accelerated degradation, together with the influence of nanoindenter tip geometry (pyramidal versus spherical), was evaluated on Absorb tubing samples. To review the feasibility of a novel co-polymer for scaffold applicaiton, the unique tubing material was comparatively assessed against Absorb, using the same testing parameters established on 4 Absorb. Finally, method of polymer synthesis and manufacture was evaluated using the same experimental technique; where both natural and synthetic polymers were tested, with results compared against those for stainless steel stents.

It was discovered that AFM was possible to quantify the very local mechanical property, Young’s modulus, of the scaffold. Nanoindentation provided a wide range of Young’s modulus data for the virgin material, depending on the load level as well as additional factors such as ageing and the polymeric structure. For degradation, it was seen, with both AFM and nanoindentation, that there was no dramatic decline in the material stiffness over the two-year period; however a decline in the material was captured with chemical analyses (GPC and DSC). For accelerated degradation, it was possible to speed up the degradation process sufficiently at an elevated temperature; however, again, there was no definite observation of decline in Young’s modulus even when the material reached a breakage state (i.e. extremely brittle). Instead, the material degradation was captured by the local stress-strain response obtained with spherical indentation, and further confirmed with chemical analyses. The novel co-polymer (PLA-PCL-PEG) did not perform adequately in comparison to Absorb, and hence requires further composition improvement. In contrast, the natural polymer (PHA) appeared to be a potential candidate for vascular scaffold application, with degradation behaviour subjected to further investigatations.
In summary, it was seen that pyramidal indentation could not accurately capture the response of PLLA; spherical indentation can be used alternatively. The stress-strain response obtained with spherical indentaiton is able to capture the material weakening with degradation at a benchtop level, in both normal and accelerated conditions. For novel polymers, it is possible to assess their credibility as a scaffolding material at an early development stage, using the techniques and the benchmark data (i.e., FDA approved Absorb material) delivered in this thesis.

Funding

British Heart Foundation (BHF).

History

School

  • Mechanical, Electrical and Manufacturing Engineering

Publisher

© Raasti Naseem

Publisher statement

This work is made available according to the conditions of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) licence. Full details of this licence are available at: https://creativecommons.org/licenses/by-nc-nd/4.0/

Publication date

2018

Notes

A Doctoral Thesis. Submitted in partial fulfilment of the requirements for the award of Doctor of Philosophy of Loughborough University.

Language

en

Usage metrics

Keywords

Exports