ABSTRACT

Heart disease is the number one cause of death in the US and a leading cause worldwide, but current medicine cannot regenerate and or repair diseased human heart tissue. Today, there is no cure for a heart attack. The vision of Directed Multiscale Assembly of Cellular Metamaterials with Nanoscale Precision (CELL-MET) Nanosystems Engineering Research Center is to change this. CELL-MET will develop tissue-engineering principles to create scalable, low-cost technologies for growing clinically significant cardiac tissues from cell-level building blocks. The research approach is to adapt and advance novel nanomanufacturing techniques to integrate a variety of functional biological structures and elements into flexible polymer scaffolds that support and guide heart cells. The goal of this project is to create cardiac patches that will someday allow for the repair of hearts damaged by a heart attack or other diseases. In addition to their potential for repairing damaged hearts, artificial cardiac tissues will be used to test the effects of heart drugs or other drugs more realistically and efficiently than is currently possible. Broader impacts will include kindergarten to post-doctoral education and training programs that will produce a robust, well-trained, world aware workforce to support the new billion dollar industries enabled by CELL-MET research. Industrial partners will work with CELL-MET to create these new industries, developing the business opportunities generated by the research breakthroughs.

CELL-MET aims to create functional, clinically significant heart tissue in the laboratory by controlling the cardiac structure across different length scales. At sizes smaller than a micron and up to the ten micron scale of cells, CELL-MET will align heart muscle cells (cardiomyocytes) and connect them to one another via special cellular structures, enabling them to contract and relax in synchrony. At the multicellular scale, it will monitor and control chemical signaling both among these cells and between them and supporting cells. At the scale of tissue constructs, CELL-MET will create highly structured networks of blood vessels lined with epithelial cells, which are needed for any thick tissue. The ten-year vision encompasses the incorporation of endocardial cells that help define the large-scale structure and electrophysiological function of the heart, as well as the valves that ensure unidirectional blood flow.
CELL-MET brings together a diverse, world-class team from Boston University, the University of Michigan, Florida International University, Harvard, Columbia, Argonne National Lab, EPFL (Switzerland), and Centro Atomico-Bariloche (Argentina). The team has expertice in semiconductors, photonics, nanotechnology, optical systems, organic molecules, cardiac biology, and cellular assembly. CELL-MET is uniquely positioned to harness the capabilities and synergies among these disciplines. CELL-MET plans to combine novel techniques for patterning molecules on the scale of 50 nm or less with nanometer resolution 3D-printed scaffolds. 3D nanoprinting technologies will produce scaffolds that Atomic Calligraphy and Organic Vapor Jet Printing will write upon to create the focal adhesion points, the places that attach the cells. Advanced tissue engineering techniques will populate these nanostructures with cardiomyocytes and other cardiac cell types to produce the living tissues.
As CELL-MET advances the technology, it will work with commercial members of its Innovation Ecosystem to create entirely new industries. Through its Education and Workforce Development programs, CELL-MET will recruit and train a robust, world aware workforce to support the industries that it creates.

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