Stem Cell-Secreted Allogeneic Elastin-Rich Matrix with Subsequent Decellularization for the Treatment of Critical Valve Diseases in the Young.

Critical valve diseases in infants have a very poor prognosis for survival. Particularly challenging is for the valve replacement to support somatic growth. From a valve regenerative standpoint, bio-scaffolds have been extensively investigated recently. While bio-scaffold valves facilitate acute valve functionality, their xenogeneic properties eventually induce a hostile immune response. Our goal was to investigate if a bio-scaffold valve could be deposited with tissues derived from allogeneic stem cells, with a specific dynamic culture protocol to enhance the extracellular matrix (ECM) constituents, with subsequent stem cell removal. Porcine small intestinal submucosa (PSIS) tubular-shaped bio-scaffold valves were seeded with human bone marrow-derived mesenchymal stem cells (hBMMSCs), cultured statically for 8 days, and then exposed to oscillatory fluid-induced shear stresses for two weeks. The valves were then safely decellularized to remove the hBMMSCs while retaining their secreted ECM. This de novo ECM was found to include significantly higher (p < 0.05) levels of elastin compared to the ECM produced by the hBMMSCs under standard rotisserie culture. The elastin-rich valves consisted of ~8% elastin compared to the ~10% elastin composition of native heart valves. Allogeneic elastin promotes chemotaxis thereby accelerating regeneration and can support somatic growth by rapidly integrating with the host following implantation. As a proof-of-concept of accelerated regeneration, we found that valve interstitial cells (VICs) secreted significantly more (p < 0.05) collagen on the elastin-rich matrix compared to the raw PSIS bio-scaffold.

Directional dependence on concomitant pressure and volume increases during left ventricular filling.

Myocardial infarction continues to be a leading cause of mortality and morbidity globally. A major challenge post-myocardial infarction is scar tissue growth, which eventually can lead to heart failure. Cardiovascular regenerative strategies to minimize scar tissue growth and promote cardiac tissue formation are currently being actively pursued via the development of cardiac patches. However, the patch must have viscoelastic properties that mimic healthy cardiac tissues to facilitate proper cardiac patch-to-cell communications. To this end, we investigated the tissue microstructure and the stress relaxation properties of the porcine left ventricle (LV) along its long and short axes using a nanoindentation technique. We found significantly higher collagen density along the long axis than the short axis (p < 0.05). We then identified a much more rapid stress relaxation along the porcine LV's short axis compared to its long axis during the diastolic filling timeframe. Therefore, these findings show that concomitant LV pressure and volume increases from blood filling during diastole are directional dependent, with its short axis responsible for increase in LV volume and the long axis responsible for increase in LV pressure. These directional-dependent stress relaxation properties are essential in the design of structurally, bio-mimetic cardiac patches to support cardiac function and regeneration.