Biological Equivalence of GGTA-1 Glycosyltransferase Knockout and Standard Porcine Pericardial Tissue Using 90-Day Mitral Valve Implantation in Adolescent Sheep

Objective There is growing interest in the application of genetically engineered reduced antigenicity animal tissue for manufacture of bioprosthetic heart valves (BHVs) to reduce antibody induced tissue calcification and accelerated structural valve degeneration (SVD). This study tested biological equivalence of valves made from Gal-knockout (GalKO) and standard porcine pericardium after 90-day mitral valve implantation in sheep. Methods GalKO (n = 5) and standard (n = 5) porcine pericardial BHVs were implanted in a randomized and blind fashion into sheep for 90-days. Valve haemodynamic function was measured at 30-day intervals. After explantation, valves were examined for pannus, vegetation, inflammation, thrombus, and tissue calcification. Results Nine of 10 recipients completed the study. There was no difference between study groups for haemodynamic performance and no adverse valve-related events. Explanted BHVs showed mild pannus integration and minimal thrombus, with no difference between the groups. Limited focal mineral deposits were detected by x-ray. Atomic spectroscopy analysis detected tissue calcium levels of 1.0 µg/mg ± 0.2 for GalKO BHVs and 1.9 µg/mg ± 0.9 for standard tissue BHVs (p = 0.4), considered to be both low and equivalent. Conclusions This is the first demonstration of biological equivalence between GalKO and standard pig pericardium. The GalKO mutation causes neither intrinsic detrimental biological nor functional impact on BHV performance. Commercial adaptation of GalKO tissue for surgical or transcatheter BHVs would remove the clinical disparity between patients producing anti-Gal antibody and BHVs containing the Gal antigen. GalKO BHVs may reduce accelerated tissue calcification and SVD, enhancing patient choices, especially for younger patients

Validation and Extension of a Fluid–Structure Interaction Model of the Healthy Aortic Valve

PURPOSE: The understanding of the optimum function of the healthy aortic valve is essential in interpreting the effect of pathologies in the region, and in devising effective treatments to restore the physiological functions. Still, there is no consensus on the operating mechanism that regulates the valve opening and closing dynamics. The aim of this study is to develop a numerical model that can support a better comprehension of the valve function and serve as a reference to identify the changes produced by specific pathologies and treatments. METHODS: A numerical model was developed and adapted to accurately replicate the conditions of a previous in vitro investigation into aortic valve dynamics, performed by means of particle image velocimetry (PIV). The resulting velocity fields of the two analyses were qualitatively and quantitatively compared to validate the numerical model. In order to simulate more physiological operating conditions, this was then modified to overcome the main limitations of the experimental setup, such as the presence of a supporting stent and the non-physiological properties of the fluid and vessels. RESULTS: The velocity fields of the initial model resulted in good agreement with those obtained from the PIV, with similar flow structures and about 90% of the computed velocities after valve opening within the standard deviation of the equivalent velocity measurements of the in vitro model. Once the experimental limitations were removed from the model, the valve opening dynamics changed substantially, with the leaflets opening into the sinuses to a much greater extent, enlarging the effective orifice area by 11%, and reducing greatly the vortical structures previously observed in proximity of the Valsalva sinuses wall. CONCLUSIONS: The study suggests a new operating mechanism for the healthy aortic valve leaflets considerably different from what reported in the literature to date and largely more efficient in terms of hydrodynamic performance. This work also confirms the crucial role that numerical approaches, complemented with experimental findings, can play in overcoming some of the limitations inherent in experimental techniques, supporting the full understanding of complex physiological phenomena

Valvulogenesis of a living, innervated pulmonary root induced by an acellular scaffold

Heart valve disease is a major cause of mortality and morbidity worldwide with no effective medical therapy and no ideal valve substitute emulating the extremely sophisticated functions of a living heart valve. These functions influence survival and quality of life. This has stimulated extensive attempts at tissue engineering "living" heart valves. These attempts utilised combinations of allogeneic/ autologous cells and biological scaffolds with practical, regulatory, and ethical issues. In situ regeneration depends on scaffolds that attract, house and instruct cells and promote connective tissue formation. We describe a surgical, tissue-engineered, anatomically precise, novel off-the-shelf, acellular, synthetic scaffold inducing a rapid process of morphogenesis involving relevant cell types, extracellular matrix, regulatory elements including nerves and humoral components. This process relies on specific material characteristics, design and "morphodynamism"