Background: Conceptually, a tissue engineered heart valve would be especially appealing in the pediatric setting since small size and somatic growth constraints would be alleviated. In this study, we utilized porcine small intestinal submucosa (PSIS) for valve replacement. Of note, we evaluated the material responses of PSIS and subsequently its acute function and somatic growth potential in the mitral position. Methods and Results: Material and mechanical assessment demonstrated that both fatigued 2ply (∼65 μm) and 4ply (∼110 μm) PSIS specimens exhibited similar failure mechanisms, but at an accelerated rate in the former. Specifically, the fatigued 2ply PSIS samples underwent noticeable fiber pullout and recruitment on the bioscaffold surface, leading to higher yield strength (p < 0.05) and yield strain (p < 0.05) compared to its fatigued 4ply counterparts. Consequently, 2ply PSIS mitral valve constructs were subsequently implanted in juvenile baboons (n = 3). Valve function was longitudinally monitored for 90 days postvalve implantation and was found to be robust in all animals. Histology at 90 days in one of the animals revealed the presence of residual porcine cells, fibrin matrix, and host baboon immune cells but an absence of tissue regeneration. Conclusions: Our findings suggest that the altered structural responses of PSIS, postfatigue, rather than de novo tissue formation, are primarily responsible for the valve's ability to accommodate somatic growth during the acute phase (90 days) following mitral valve replacement. Impact Statement Tissue engineered heart valves (TEHVs) offer the potential of supporting somatic growth. In this study, we investigated a porcine small intestinal submucosa bioscaffold for pediatric mitral heart valve replacement. The novelty of the study lies in identifying material responses under mechanical loading conditions and its effectiveness in being able to function as a TEHV. In addition, the ability of the scaffold valve to support acute somatic growth was evaluated in the Baboon model. The current study contributes toward finding a solution for critical valve diseases in children, whose current prognosis for survival is poor.
Keywords: heart valve; porcine small intestinal submucosa (PSIS); somatic growth; tissue engineering; valve function.