Page 137 - Tailoring Electrospinning Techniques for Regenerative Medicine - Marc Simonet

50’000 cycles at 10% elongation. A er γ-sterilization the fatigue resistance was reduced to ~10’000 cycles. At a heart rate of 70 bpm this would correlate to a valve functionality of less than 2.5 hours. This behavior was confirmed in the pulse duplicator. The valves prepared from PCL started to disintegrate in the first hour when tested under elevated pulmonary conditions. This emphasized the role of in-vitro testing prior to in-vivo valve implantation.
In contrast, the PCL2kU4Un showed no signs of failure over 3 million cycles at 10% elongation and this functionality was maintained a er sterilization. The promising fatigue properties of PCL2kU4Un correlated with the in-vitro hemodynamic valve performance. All tested PCL2kU4Un valves endured elevated pulmonary condition for 20 hours without any signs of damage and stable read-outs. For future testing, the design of the pulse duplicator test setup should be adapted by e.g. suturing the valve into a sealed valve conduit to stop the leakage alongside the stent. This would allow to measure with pulmonary and aortic conditions rather than to compensate for the leakage with increasing the pressure regime.
One PCL2kU4Un valve was consecutively tested at increased pressure regimes, toward simulating aortic conditions for another 40 h. Remarkably, the valve was still fully functional a er these 60 h with no signs of prolapse or deterioration. Opening and closing behavior was excellent. Because of good in-
vivo performance the PCL2kU4Un valve was selected for further in-vivo evaluation.
Cell ingrowth is crucial for viability and, therewith,
long-term functionality of the valve in-vivo.
Electrospun sca olds o en do not allow su icient
cell ingrowth due to their too small pore sizes inside
the sca old, mostly corresponding to sca olds with sub-micrometer to small micrometer sized fibers.26,27
There are means to allow su icient cell ingrowth
even with sub-micrometer fibers, by e.g. including
pore templates or sacrificial fibers.11,28,29 However, all
these techniques reduce the mechanical integrity of
the sca old. Our approach was to increase the fiber
diameter to enable cell infiltration.27 Selecting the electrospinning parameters to obtain fibers with a
diameter of 5 μm, allowed cells to migrate into and
proliferate within the electrospun sca olds when
implanted as pulmonary valve into sheep. The
fibrous valvular sca olds provided su icient stability
to carry initial mechanical loading. Additionally, the 6 sca olds were fibrous and porous enough for cells
to adhere and migrate into the sca old. First neo- tissue formation was seen a er 2 weeks which is an important finding for in-situ tissue engineering. It is crucial that the degradation behavior of the material matches the rate of tissue formation. In this study, there was a misbalance between tissue formation and sca old degradation resulting in gra failure within 5 weeks a er implantation. SEM pictures (Figure 6.8) on the explants a er 4 and
FROM A POLYMER TOWARDS AN IN-SITU TISSUE ENGINEERED HEART VALVE
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