Abstract
Introduction: To investigate enhanced treatment options for critical mitral valve disease in children, we implanted a bio-scaffold mitral valve comprising of porcine small intestinal submucosa (PSIS) in a juvenile baboon model. Hypothesis: New tissue formation would be accelerated at physical connections between the replacement bio-scaffold valve and native cardiac tissues, due to direct extracellular matrix (ECM) communications. Methods: Juvenile baboons (n=2) were implanted with a hand-made bicuspid PSIS (Cormatrix, Roswell, GA) mitral valve. The PSIS valves were excised at 11- and 20-months post-implantation. Images of histological stains (Movat’s Pentachrome; Alizée Pathology, Inc., Thurmont, MD) were subsequently spatially mapped for ECM quantification (MATLAB; Mathworks, Natick, MA). Results: PSIS bio-scaffold mitral valves (11- and 20-months post-implantation) facilitated complete regeneration of neochordae. The neochordae seamlessly integrated into the papillary muscles and left ventricular insertion sites ( Figure 1A, E ). We also found that with an increase in implantation duration of ~ 9 months, the collagen, proteoglycan and elastin content (per mm 2 ; Figure 1B-D, F-H ) had a fold-change of 6.96, 18.42 and 4.94, respectively. Conclusions: Our findings suggest that the PSIS bio-scaffold mitral valve apparatus can regenerate neochordae without the need for any biochemical or biomechanical treatment. Nonetheless, other valve spatial areas of importance (e.g. leaflets) will require additional strategies. As a next step, we will produce oscillatory flow-conditioned, stem cell-derived ECM, to accelerate tissue regeneration. The mechanical parameters that we computed to permit physiological oscillatory flow conditions are an oscillatory shear index (OSI) of 0.23 and time averaged bio-scaffold shear stress (TAB-SSS) of 4.6 dynes/cm 2 . Acknowledgements: AHA Award ID: 16GRNT31090009; The Miami Research Heart Institute; FIU-UGS DYF.
Published Version
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