Hybrid Electrospun Transcatheter Aortic Heart Valves for Tissue Engineering Applications

Taylor, Jade

Hybrid Electrospun Transcatheter Aortic Heart Valves for Tissue Engineering Applications

Master Thesis

2022

Abstract

Bioprosthetic and mechanical heart valves are suboptimal due to both calcific degeneration and the need for lifelong anticoagulation treatment. Tissue engineering (TE) has the potential to overcome these and other shortcomings by providing viable valves capable of growth, remodelling, and repair. Electrospinning has gained popularity as one of the methods used to create porous, threedimensional TE scaffolds that mimic the extracellular matrix (ECM) and allow for cellular ingrowth into the construct. The aim of the current study was to investigate the feasibility of producing electrospun scaffolds with both degradable and reinforcing, non-degradable, fibres to improve mechanical properties and allow for improved control over degradation rates to avoid catastrophic valve failure due to premature valve degradation and inadequate tissue ingrowth. Degradable (DegraPol15®; DP15), non-degradable (Pellethane®), and hybrid (dual) scaffolds (± 1:1 mass ratio of DP15 and Pellethane®) were electrospun and characterised morphologically and mechanically before and after various periods of hydrolytic degradation. Transcatheter aortic heart valves (23 mm) with DegraPol®, Pellethane®, and hybrid leaflets respectively, were fabricated by means of bonding and suturing into balloon expandable transcatheter stents and tested in vitro at left heart conditions to determine hydrodynamic performance and durability. Ultimate tensile strength (UTS) decreased as electrospun scaffolds degraded, with DegraPol® exhibiting a more rapid decrease in UTS than hybrid scaffolds after six weeks of incubation (57 ± 5% vs 24 ± 10%). The same trend was seen in the distinct reduction of maximum elongation of the scaffolds (35 ± 5% and 18 ± 8 %) . Pellethane® exhibited a reduction in both UTS and % elongation close to that of hybrid scaffolds (27 ± 6% and 13 ± 6% respectively) with the Young's modulus of all scaffolds remaining nearly unaffected by the hydrolytic degradation. Hybrid scaffolds had suture retention strength similar to DegraPol®, however, hybrid scaffolds unexpectedly had the lowest tear strength (4.7 ± 0.29 N/mm) with Pellethane® scaffolds displaying superior strength in both tear strength (13.53 ± 0.35 N/mm) and suture retention strength (16.13 ± 0.8 N/mm longitudinally). In terms of valve hydrodynamic performance, all valves had an average effective orifice area (EOA) larger than 2 cm2 and pressure gradients lower than 8mmHg with no significant difference between the groups in either of these measurements. Pellethane® and hybrid valves both had lower regurgitation fractions than DegraPol® valves (30.3 ± 5.3% 28.6 ± 1.5% and 56.4 ± 4.4% for Pellethane®, hybrid and DegraPol® valves respectively), with high (>20%) values resulting from inherent material porosity shown by water permeability tests. With regards to valve durability, DegraPol® valve leaflets failed before adequate testing conditions could be reached while Pellethane® valves lasted for ±40 million cycles and were removed before failure. Hybrid valves lasted for an intermediate average of 7.0 ± 2.3 million cycles at 100 mmHg. The study shows that the polymers can be dual spun from degradable and non-degradable polymers to produce hybrid scaffolds which can potentially be used, with further development, in tissue engineering applications such as heart valves when the degradable component may lack sufficient physical strength.

Keywords

Biomedical Engineering

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