(G-246) Solid Mechanical Properties of Dehydrated, Engineered Allogeneic Elastin-Rich Valves for Somatic Growth Support Compared to the Core Bio-scaffold

Introduction:: Congenital heart defects are one of the most common types of birth defects in the United States. These defects encompass a variety of affected areas, such as atrioventricular, ventricular, or valvular defects. Infants born with critical congenital heart valve defects have limited treatment options due to unavailability of small prosthetic valves and the inability of these prosthetic valves to support somatic growth. A bio-scaffold valve, porcine small intestinal submucosa (PSIS) is used in the compassionate care of children with critical congenital heart valve defects which provides a temporary solution, but ultimately fails due to a hostile immune response. Therefore, our lab has seeded PSIS with human bone marrow-derived stem cells (hBMSCs), which produces an allogeneic elastin-rich layer onto the scaffold after dynamic oscillatory flow culture, that promotes accelerated de novo valve tissue growth by chemotaxis, which has the potential to avoid the hostile response. However, the necessary lengthy liquid culture to create these engineered valves causes the construct material to distend, increasing the risk of valve prolapse if implanted. Thus, we aim to correct its mechanical properties to those of core PSIS, which can support valve functionality for at least 3 months, which is the timeframe that we expect complete valve regeneration with our elastin-rich valve.


Materials and Methods:: Raw PSIS and our dehydrated elastin-rich valve underwent uniaxial tensile testing. A raw PSIS valve was cut into strips, rehydrated for about 5 minutes in DI water, and tested (n=4/orientation). To produce the dehydrated elastin-rich valve, hBMMSCs were cultured, statically seeded onto PSIS for 8 days and oscillatory flow dynamically cultured for 14 days. Next, the valves were decellularized using 1% Triton X-100, submerged in 57% glycerol–DI for dehydration, and finally cut into strips and tested (n=2/orientation).


Results, Conclusions, and Discussions:: The average axial stiffness and maximum stress of the raw PSIS valves were found to be 749.24 ± 80.06 MPa and 52.26 ± 6.59 MPa respectively. The axial stiffness and maximum stress of the dehydrated elastin-rich valves were found to be 239.99 ± 14.77 MPa and 26.88 ± 2.38 MPa respectively. In the circumferential orientation, raw PSIS had an average stiffness of 92.50 ± 28.07 MPa and max stress of 13.47 ± 1.03 MPa while the corresponding values for the dehydrated elastin-rich valve were 29.86 ± 4.55 and 6.38 ± 0.25. It was found that the groups were statistically significantly different (p < 0.05) in the following measurements: axial stiffness, axial max stress, and circumferential max stress (Table 1). Our immediate next steps will be focusing on performing hydrodynamic testing to assess the fluid mechanics-based functionality of the dehydrated elastin-rich valve. Future work will afterwards focus on optimizing the engineered valve’s hydrodynamic properties to be comparable to the raw PSIS valve to ensure that the elastin-rich valves can last for at least 3 months with strong valve hydrodynamic functionality. This will enable the valve to regenerate fully in the host by avoiding the hostile immune response and thus being able to support the subsequent somatic growth in the host.


Acknowledgements (Optional): : We hereby acknowledge the Miami Heart Research Institute for funding this project.

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