Thesis

Towards advanced manufacturing for personalised vascular grafts

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Awarding institution
  • University of Strathclyde
Date of award
  • 2024
Thesis identifier
  • T16961
Person Identifier (Local)
  • 201873344
Qualification Level
Qualification Name
Department, School or Faculty
Abstract
  • Surgical repair of aortic pathologies involves synthetic tubular grafts generally made of a polyester fabric. Despite being the gold-standard, such grafts do not readily endothelialise and are unable to mimic the mechanical behaviour and intricate anatomical geometry of the native aorta, contributing to suboptimal haemocompatibility, haemodynamic disruption, and long-term cardiovascular-related complications. Moreover, to date, vascular graft research has predominantly focussed on developing small diameter conduits (<6 mm) with little attention paid to larger grafts. Therefore, the primary aims of this thesis were to develop an aortic graft substitute that addresses the main limitations of the current graft technologies: (1) mechanically matches aortic tissue, (2) closely mimics the patient’s anatomy, and (3) promotes endothelialisation. To achieve this, hydrogels in combination with stereolithography (SLA) 3D-printing were investigated. Alginate, a natural monomer derived from seaweed, was first investigated due to its ease of gelling ability in the presence of divalent cations. However, single-networked, calcium-crosslinked alginate hydrogels exhibited poor elastic properties (strength: 0.02 ± 0.006 MPa, stiffness: 0.05±0.004 MPa, elongation at break: 51.60 ±11.66%) when compared to aortic tissue data reported in the literature. Therefore, to enhance the mechanical properties, a synthetic polyethylene glycol diacrylate (PEGDA) monomer was incorporated to create an interpenetrating polymer network (IPN). Moreover, PEGDA in the presence of a photoinitiator enables photopolymerisation, rendering the IPN suitable for SLA 3D-printing. The alginate:PEGDA IPN hydrogels both moulded and 3D-printed demonstrated strength (moulded: 0.39 ±0.05 MPa; 3D-printed: 0.34 ±0.05 MPa) and stiffness (moulded: 1.61 ±0.19 MPa; 3D-printed: 1.79 ±0.19 MPa) within range of the human aorta. Tubular conduits of similar dimensions to the human aorta were also fabricated via moulding and SLA 3D-printing, with the latter facilitating the fabrication of more complex, patient-specific structures. Finally, given the poor cell adhesion of both alginate and PEGDA monomers, an arginine-glycine-aspartic acid (RGD)-based peptide was synthesised and incorporated within each individual monomer, to biofunctionalise the IPN for endothelialisation. Alginate:RGD showed successful endothelial cell adhesion and coverage on the hydrogel’s surface. However, this was not the case with the PEGDA:RGD hydrogel. Furthermore, incorporating the RGD peptide to the alginate:PEGDA IPN proved to be challenging due to significant phase separation during hydrogel synthesis, and further work is required to optimise this. Nonetheless, this work shows great promise towards the development of more compliant, patient-specific aortic grafts.
Advisor / supervisor
  • McCormick, Christopher
  • Shu, Will
Resource Type
Note
  • This thesis was previously held under moratorium from 5th June 2024 until 5th June 2026.
DOI
Date Created
  • 2023
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