Dr. Nenad Bursac - Tissue Engineering for Remuscularization of The Failing Heart

Dr. Nenad Bursac - Tissue Engineering for Remuscularization of The Failing Heart Abstract: In this presentation, I will review our recent progress on engineering of functional heart muscle tissues for applications in disease modeling, drug development, and regenerative therapy. I will first describe a relatively simple, yet scalable methodology for engineering of human pluripotent stem cells (hPSCs) into highly functional cardiac tissues (named “cardiobundles” and “cardiopatches”) that possess levels of electrical and mechanical maturation approaching those of native adult myocardium. Through an optimized combination of cells, biomaterials, and dynamic culture conditions, this platform enables significant scale-up of cardiac tissue dimensions (from 5mm x 0.25mm to clinically relevant 40mm x 40mm) while preserving robust functional output and highly uniform structure. When implanted in dorsal window chambers in nude mice or onto the epicardium of nude rats, human cardiopatches exhibit robust survival, vascularization, and maintenance of electrophysiological properties. Incorporation of hPSC-derived endothelial or epicardial cells within cardiopatches leads to their rapid pre-vascularization in vitro without the loss of electrical or mechanical function. Pre-formed capillary cord structures in these tissue constructs develop into highly branched lumenized networks of blood vessels that successfully anastomose with host vasculature in vivo. Together, these studies provide a strong foundation for our ongoing tests of cardiopatch therapy in a large animal model of ischemic heart disease. Bio: Dr. Nenad Bursac is a Professor of Biomedical Engineering, Cell Biology, and Medicine at Duke University and one of the pioneers and leaders of the cardiac tissue engineering field. In 1999, as a member of Dr. Robert Langer’ group at MIT, he demonstrated the first engineering of functional heart tissues using mammalian cardiomyocytes. His postdoctoral research with Dr. Leslie Tung at Johns Hopkins University resulted in new methods to control architecture and function of 2- and 3-dimensional heart cell cultures. Currently, Dr. Bursac's research involves use of cell, tissue, and genetic engineering techniques and electrophysiological and biomechanical studies to advance fields of somatic and stem cell based therapies for heart and skeletal muscle disease. For the last 20 years, Dr. Bursac’s work has pushed the boundaries of the field by demonstrating a number of “firsts”, including: the first use of bioreactors for functional cardiac tissue engineering; the first studies of electrophysiology and arrhythmias in engineered heart tissues; the first engineering of anisotropic cardiac tissue patch and methods to control patch anisotropy; the most functionally advanced mouse cardiac tissue patch; the first engineering of highly functional, large (40mmx40mm) heart tissues from human pluripotent stem cells; first engineering of functional human skeletal muscle tissues from primary and pluripotent stem cells; and first engineering of biosynthetic excitable cells and tissues for studies and treatment of cardiac arrhythmias and heart failure. Dr. Bursac has authored more than 100 scientific manuscripts, presented over 120 invited talks, and has mentored more than 30 PhD students and postdoctoral and medical fellows. He codirects Regeneration Next Initiative at Duke University. He is a recipient of the Stansell Family Distinguished Research Award, Mendel Center Award, and Stem Cell Innovation Award. In 2014, Dr. Bursac was the president of the North Carolina Tissue Engineering and Regenerative Medicine Society. Since 2015, Dr. Bursac has been a Fellow of American Institute for Medical and Biological Engineering. He has served on various NIH grant review panels and is a member of editorial boards of Nature Scientific Reports and NPJ Regenerative Medicine.