Tissue-Engineered Heart Valves: A Call for Mechanistic Studies

Heart valve disease carries a substantial risk of morbidity and mortality. Outcomes are significantly improved by valve replacement, but currently available mechanical and biological replacement valves are associated with complications of their own. Mechanical valves have a high rate of thromboembolism and require lifelong anticoagulation. Biological prosthetic valves have a much shorter lifespan, and they are prone to tearing and degradation. Both types of valves lack the capacity for growth, making them particularly problematic in pediatric patients. Tissue engineering has the potential to overcome these challenges by creating a neovalve composed of native tissue that is capable of growth and remodeling. The first tissue-engineered heart valve (TEHV) was created more than 20 years ago in an ovine model, and the technology has been advanced to clinical trials in the intervening decades. Some TEHVs have had clinical success, whereas others have failed, with structural degeneration resulting in patient deaths. The etiologies of these complications are poorly understood because much of the research in this field has been performed in large animals and humans, and, therefore, there are few studies of the mechanisms of neotissue formation. This review examines the need for a TEHV to treat pediatric patients with valve disease, the history of TEHVs, and a future that would benefit from extension of the reverse translational trend in this field to include small animal studies.