Engineering the biomechanics of PVA/gelatin cryogels for coronary artery tissue replacements

Fegan, Katie L (2023). Engineering the biomechanics of PVA/gelatin cryogels for coronary artery tissue replacements. University of Birmingham. Ph.D.

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Abstract

With coronary artery disease remaining the leading cause of death worldwide, the design and manufacture of clinically-viable synthetic coronary artery grafts remains a fundamental healthcare challenge. It is widely accepted that vascular mimicking materials (VMMs) should emulate the heterogeneous biomechanical and biological functions of the multi-layered artery wall to ensure long-term patency post-implantation. However, few VMMs can adequately meet these complex design requirements. Poly(vinyl alcohol) (PVA)/gelatin cryogels are prospective VMMs owing to their combined mechanical (PVA) and biointegrative (gelatin) features, but their development thus far has been limited to homogenous constructs. This thesis aimed to combine the mechanical characterisation of PVA/gelatin cryogel with the finite element modelling of heterogeneous coronary artery grafts to inform the design of biomimetic synthetic grafts – an approach that is critically underused in the field of cardiovascular tissue engineering.

In addition to exhibiting a hyperelastic stiffening response when loaded up to 50% strain, the linear elastic (E = 144.4–334.4 kPa at 15–20% strain) and dynamic viscoelastic (E′ = 182.9–444.4 kPa and E′′ = 24.8–39.5 kPa between 0–10 Hz) parameters of PVA/gelatin cryogel fell within the ranges reported for coronary arteries. These findings not only extend current understanding of PVA/gelatin mechanics, but further perpetuate its use as a mechanically-relevant VMM.

The biomechanics of four multi-layered, laminated PVA/gelatin cryogel graft designs were explored at systolic pressure using a hyperelastic finite element (FE) framework. FE analysis was used to match the transmural stress and strain distributions of PVA/gelatin grafts to the coronary intima, media and adventitia through layer-specific variation of cryogel. While the magnitudes of stress, strain and absolute compliance of all PVA/gelatin grafts exceeded that of the coronary artery, this thesis demonstrated for the first time the potential of FE analysis to design stress- and compliance-matched coronary artery grafts; this work not only supports the development of PVA/gelatin grafts, but supports the development of all hyperelastic VMMs intended for use as coronary artery grafts.

Finally, this thesis investigated a previously unexplored research theme in cardiovascular tissue engineering: the role of interface design on achieving bioinspired, functionally-graded coronary artery grafts. The FE framework was extended to assess the impact of interface radius, amplitude and frequency of an elastic lamellae-inspired sinusoidal interface on stress distribution and graft compliance. While the radius had the largest influence on compliance, larger amplitudes also increased the mean compliance by increasing the extent of non-uniform radial deformation around the lumen. Critically, transmural stress patterns were continuously graded (’phased’) as a function of interface amplitude and frequency, illustrating a novel approach to designing biomimetic, functionally graded synthetic grafts. By qualitatively assessing the impact that interface-induced stress may have on endothelialisation, this thesis has taken a novel and important step towards bridging the gap between the mechanical and biological characterisation of heterogeneous PVA/gelatin grafts.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):