Tissue-Engineered Heart Valves: A Call for Mechanistic Studies

Abstract

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.

Impact of modified gelatin on valvular microtissues

“…One of the most prevalent heart valve disease in Western countries is calcific aortic valve disease. Valve repair or replacement remains the only available clinical treatment option to date (Blum, Drews, & Breuer, ). Next generation therapies are needed to improve patient outcome and quality of life and limit the need for valvuloplasty and replacement therapy.…”

Polyisobutylene-Based Thermoplastic Elastomers for Manufacturing Polymeric Heart Valve Leaflets: In Vitro and In Vivo Results

“…Tissue-engineered heart valves strive to overcome the limitations of mechanical and bioprosthetic valves, because they are living tissues capable of active remodeling and self-repair [16]. However, more studies are required to determine the optimal composition, manufacturing technique, and biofunctionalization of the selected scaffolds [17]. Functional properties of mechanical heart valves may be addressed by additional coatings able to change the roughness and wettability of the product and control the resultant hemocompatibility and biocompatibility [18,19].…”

Sheep-Specific Immunohistochemical Panel for the Evaluation of Regenerative and Inflammatory Processes in Tissue-Engineered Heart Valves

“…Heart valve TE research has predominantly focused on optimizing valvular graft design and in vitro culture protocols ( 6 – 11 , 33 ), and relatively little mechanistic data is available regarding the in vivo biological events that drive remodeling and integration of TE valves after implantation ( 34 ). In vivo testing of heart valves is typically performed in sheep, as this is the FDA-approved animal model for preclinical evaluation of heart valves.…”