Development and Evaluation of a Novel Combined Perfusion Decellularization Heart-Lung Model for Tissue Engineering of Bioartificial Heart-Lung Scaffolds

Abstract

<h3>Purpose</h3> Tissue engineering provides a new concept for organ and tissue replacement, and may represent a new approach to generate native-like substitutes for extensive cardiothoracic disorders. Bioengineered transplantable heart-lung scaffolds could be potentially lifesaving in a large number of congenital and acquired cardiothoracic disorders including terminal heart-lung disease. The aim of this project was to evaluate mechanical and biochemical properties of the native heart and lung, to optimize a decellularization protocol to obtain a suitable heart-lung acellular grafts that can be re-seeded with cells and implanted without need of immunosuppression, and potentially to be able to create an artificial heart-lung scaffold made up by decellularization of native heart-lung blocks seeded with an appropriate source of mononuclear or stromal cells to accurately mimic the structure and function of a native heart-lung substitute. <h3>Methods</h3> We decellularized rat hearts (n = 5) and heart-lung organ-blocs (n = 5) by coronary and tracheal perfusion with ionic detergents in a modified Langendorff circuit. We confirmed decellularization by histology, transmission electron microscopy and fluorescence microscopy. <h3>Results</h3> In the present project we were able to achieve 100% decellularization of the heart and heart-lung organ-bloc <i>(Figure 1)</i>. Decellularized heart-lung organ-blocs lacked intracellular components but retained specific collagen fibers and mechanical integrity. <h3>Conclusion</h3> We present a novel model of a combined perfusion and decellularization of the heart and heart-lung organ-blocs. This model is a first step in the direction of creating bioengineered transplantable heart-lung scaffolds. We believe that further developing of this technology could provide a life-saving conduit, significantly reducing the risks of heart-lung failure surgery, and improve post-operative quality of life.