Scaffold-Free Tissue-engineered Cardiac Patch Processed with a novel 3D Bio-Printer for Myocardial Restoration

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ABSTRACT The ultimate goal of this project is to develop a tissue-engineered heart to treat patients of end-stage heart failure by replacing the diseased heart. As the initial step, we are developing a tissue-engineered cardiac patch to promote in-situ myocardial regeneration and functional restoration. Heart failure is a major health problem with increasing prevalence, caused in part by increased survivors from acute myocardial infarction, increased life expectancy, and lifestyle choices. There are 53,000 deaths per year related to heart failure. While heart transplantation is currently a gold standard therapy for the treatment of severe heart failure, it only serves for about 2,000 patients per year in the United States due to a shortage of donors. Mechanical support technologies such as left ventricular assist device (LVAD) have been developed for treatment of advanced heart failure as an alternative to heart transplant. A major issue for LVAD therapy is that LVADs are designed to support the left-side heart only but not for right-side heart and that currently there is no durable long-term right ventricular assist device available. Another surgical technique called Surgical Ventricular Restoration (SVR) is also an important strategy for heart failure treatment. Most SVR techniques utilize a large synthetic cardiac patch to restore the geometry of the heart. However, the large inert patches are rapidly encapsulated by the host and do not restore myocardial function, which limit recovery of heart functions. In order to improve the outcomes of surgical treatments and the quality of life of advanced heart failure patients, it is critical to develop a new biomaterial that contributes restoring the heart function. Recently, a novel three dimensional (3D) bio-printer has been invented. The 3D bio-printer is a robotic system that facilitates the fabrication of 3D cellular structures by placing cell spheroids in needle arrays based on pre- designed 3D data. This system allows to create any shape of 3D structure using any desired cells/biomaterials in any coordinate location. No study has been done using this system in the field of cardiac surgery while several applications in other organs (e.g. blood vessel, liver) have started showing promising results. In this proof-of-concept study, we will create a scaffold-free 3D tissue-engineered cardiac patch. The patch will consist of 3 layers: endothelial cells, cardiomyocytes, and adventitial fibroblasts. The patches will be tested in a porcine right ventricular patch replacement model and assessed with Electromechanical mapping, Cardiac Magnetic Resonance Imaging, as well as histological examinations. The goal of this preliminary study is to demonstrate that the new tissue-engineered patch 1) provides the decent durability and strength in a porcine preparation, 2) provides enhanced site-specific host cell repopulation, and 3) restores functional myocardium. At the conclusion of the proposed study and future studies of the project, we could provide a promising material for in-situ myocardial regeneration, which could eventually save over 50,000 patients dying every year from advanced heart failure.