Key result
Improved geometry of decellularized tissue engineered heart valves using a bioreactor insert resulted in competent hydrodynamic functionality, fatigue resistance up to 12 million cycles, and decreased radial tissue compression.
Modifying the geometry of decellularized tissue engineered heart valves using a bioreactor insert reduces radial tissue compression and maintains valve competence in vitro, offering a potential solution to leaflet retraction.
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May mitigate leaflet retraction in engineered valves in vitro; leaves open in vivo efficacy and clinical translation.
Recent studies on decellularized tissue engineered heart valves (DTEHVs) showed rapid host cell repopulation and increased valvular insufficiency developing over time, associated with leaflet shortening. A possible explanation for this result was found using computational simulations, which revealed radial leaflet compression in the original valvular geometry when subjected to physiological pressure conditions. Therefore, an improved geometry was suggested to enable radial leaflet extension to counteract for host cell mediated retraction. In this study, we propose a solution to impose this new geometry by using a constraining bioreactor insert during culture. Human cell based DTEHVs (n = 5) were produced as such, resulting in an enlarged coaptation area and profound belly curvature. Extracellular matrix was homogeneously distributed, with circumferential collagen alignment in the coaptation region and global tissue anisotropy. Based on in vitro functionality experiments, these DTEHVs showed competent hydrodynamic functionality under physiological pulmonary conditions and were fatigue resistant, with stable functionality up to 16 weeks in vivo simulation. Based on implemented mechanical data, our computational models revealed a considerable decrease in radial tissue compression with the obtained geometrical adjustments. Therefore, these improved DTEHV are expected to be less prone to host cell mediated leaflet retraction and will remain competent after implantation.
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Sanders et al. (2015) studied Heart valve replacement (in vitro model) (n=5). Improved geometry using a constraining bioreactor insert vs. Original valve geometry was evaluated on Hydrodynamic functionality and radial tissue compression. Improved geometry of decellularized tissue engineered heart valves using a bioreactor insert resulted in competent hydrodynamic functionality, fatigue resistance up to 12 million cycles, and decreased radial tissue compression.
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