Instrumented cardiac microphysiological devices via multimaterial three-dimensional printing

• Published in: Nature materials 2017-03, Vol.16 (3), p.303-308
• Main Authors: Lind, Johan U., Busbee, Travis A., Valentine, Alexander D., Pasqualini, Francesco S., Yuan, Hongyan, Yadid, Moran, Park, Sung-Jin, Kotikian, Arda, Nesmith, Alexander P., Campbell, Patrick H., Vlassak, Joost J., Lewis, Jennifer A., Parker, Kevin K.
• Format: Article
• Language: English
• Subjects: 3-D printers; 631/1647/277; 631/61/2035; 639/166/985; 639/301/1005/1009; 639/301/54/994; Biomaterials; Biomedical engineering; Condensed Matter Physics; Devices; Drugs; Electronics; Fabrication; Heart; Human behavior; Laminar; letter; Materials Science; Medical equipment; Myocardium - cytology; Nanotechnology; Optical and Electronic Materials; Printing, Three-Dimensional - instrumentation; Self assembly; Sensors; Stem cells; Three dimensional printing; Tissue Array Analysis - instrumentation; Tissue engineering; Tissues
• ISSN: 1476-1122; 1476-4660
• DOI: 10.1038/nmat4782

Heart-on-a-chip devices with integrated strain gauges for direct readout of tissue contractile strength allow for multiplexed drug-dose experiments and studies of functional maturation of cardiac tissue. Biomedical research has relied on animal studies and conventional cell cultures for decades. Recently, microphysiological systems (MPS), also known as organs-on-chips, that recapitulate the structure and function of native tissues in vitro , have emerged as a promising alternative 1 . However, current MPS typically lack integrated sensors and their fabrication requires multi-step lithographic processes 2 . Here, we introduce a facile route for fabricating a new class of instrumented cardiac microphysiological devices via multimaterial three-dimensional (3D) printing. Specifically, we designed six functional inks, based on piezo-resistive, high-conductance, and biocompatible soft materials that enable integration of soft strain gauge sensors within micro-architectures that guide the self-assembly of physio-mimetic laminar cardiac tissues. We validated that these embedded sensors provide non-invasive, electronic readouts of tissue contractile stresses inside cell incubator environments. We further applied these devices to study drug responses, as well as the contractile development of human stem cell-derived laminar cardiac tissues over four weeks.