Page 131 - Tailoring Electrospinning Techniques for Regenerative Medicine - Marc Simonet

original strength, whereas all PCL sca olds lost more than two-third of their original strength already a er 1000 cycles (Figure 6.2b). When compared to PCL sca olds, PCL2kU4Un sca olds not only maintained their mechanical properties over the tested cycles better, they also required ~5 times less force to be stretched to 10% elongation.
6.4.2 In-vitro hemodynamic behavior
Valves made from PCL could not withstand elevated pulmonary conditions and started to disintegrate already in the first hours. A er 2 hours, the cardiac output over the valve decreased from 3 to 2 l/min and the mean pressure dropped from 15 to 10 mmHg (Figure 6.4a and b). Along with the destruction of the leaflets a er 20 h, the PCL valve showed a significant decrease in cardiac output (60%) and mean pressure (62%) (p<0.01). With 1.7 cm2 at the beginning to 1.6 cm2 a er 20 hours, the calculated e ective orifice area (AEO) remained stable. Due to this fast failure, the PCL valves were not tested at aortic pressures. In contrast to PCL sca olds, the cardiac output at 50/25 and 120/80 mmHg of the valves electrospun from PCL2kU4Un showed no significant changes and maintained stable at 3 l/min. The mean pressure at both conditions had a significant, but not relevant decrease (8% for 50/25 and 6% for 120/80 mmHg). PCL2kU4Un valves showed no signs of failure, a complete opening and closure of the valve leaflets and no prolapse a er 20 h of testing (see Figure
6.4c and d). The AEO at 50/25 mmHg changed from 2.6 to 2.2 cm2, with 2.1 cm2 at the beginning to 2.2 cm2 a er 20 hours the AEO at 120/80 mmHg remained stable. Notably a value well above the minimum requirements for aortic valve prostheses according to ANSI/AAMI ISO 5840:2005 Cardiovascular Implants – Cardiac Valve Prostheses of 1.6 cm2.
7.4.3 In-situ valve performance
Valve preparation and implantation
The PCL2kU4Un valve was selected for implantation
in sheep, since this heart valve showed promising
in-vitro hemodynamic results. All implantations
were successful. The total bypass time was 51.2±8.1
minutes. At implantation the echocardiographic
evaluation of the valves showed an adequate
function of all implanted heart valves. All leaflets
moved properly without any signs of stenosis.
There was no regurgitation in one case and mild regurgitation (grade I) in 9 cases. 6
Valve explantation and characterization
One animal died 4 weeks post implantation due to gra failure. At 2 (n=2) and 3 weeks (n=2) follow-up, the function of all heart valve sca olds was adequate, showing regurgitation grade I without any sign of stenosis. A er 4 (n=4) and 5 weeks (n=2) follow-up an increase in regurgitation was seen to grade III-IV in all cases.
FROM A POLYMER TOWARDS AN IN-SITU TISSUE ENGINEERED HEART VALVE
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