title: Microfabricated perfusable cardiac biowire: a platform that mimics native cardiac bundle.
abstract: Tissue engineering enables the generation of three-dimensional (3D) functional cardiac tissue for pre-clinical testing in vitro, which is critical for new drug development. However, current tissue engineering methods poorly recapitulate the architecture of oriented cardiac bundles with supporting capillaries. In this study, we designed a microfabricated bioreactor to generate 3D micro-tissues, termed biowires, using both primary neonatal rat cardiomyocytes and human embryonic stem cell (hESC) derived cardiomyocytes. Perfusable cardiac biowires were generated with polytetrafluoroethylene (PTFE) tubing template, and were integrated with electrical field stimulation using carbon rod electrodes. To demonstrate the feasibility of this platform for pharmaceutical testing, nitric oxide (NO) was released from perfused sodium nitroprusside (SNP) solution and diffused through the tubing. The NO treatment slowed down the spontaneous beating of cardiac biowires based on hESC derived cardiomyocytes and degraded the myofibrillar cytoskeleton of the cardiomyocytes within the biowires. The biowires were also integrated with electrical stimulation using carbon rod electrodes to further improve phenotype of cardiomyocytes, as indicated by organized contractile apparatus, higher Young's modulus, and improved electrical properties. This microfabricated platform provides a unique opportunity to assess pharmacological effects on cardiac tissue in vitro by perfusion in a cardiac bundle model, which could provide improved physiological relevance.
authors.affiliation: Department of Chemical Engineering and Applied Chemistry, University of Toronto, 164 College St, Rm 407, Toronto, ON M5S 3G9, Canada. m.radisic@utoronto.ca.
authors.forename: Yun
authors.initials: Y
authors.lastname: Xiao
authors.forename: Boyang
authors.initials: B
authors.lastname: Zhang
authors.forename: Haijiao
authors.initials: H
authors.lastname: Liu
authors.forename: Jason W
authors.initials: JW
authors.lastname: Miklas
authors.forename: Mark
authors.initials: M
authors.lastname: Gagliardi
authors.forename: Aric
authors.initials: A
authors.lastname: Pahnke
authors.forename: Nimalan
authors.initials: N
authors.lastname: Thavandiran
authors.forename: Yu
authors.initials: Y
authors.lastname: Sun
authors.forename: Craig
authors.initials: C
authors.lastname: Simmons
authors.forename: Gordon
authors.initials: G
authors.lastname: Keller
authors.forename: Milica
authors.initials: M
authors.lastname: Radisic
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry / Q000378:metabolism*; D019149:Bioreactors; D002478:Cells, Cultured; D055119:Elastic Modulus; D004558:Electric Stimulation; D004566:Electrodes; D053595:Embryonic Stem Cells / Q000166:cytology; D005782:Gels / Q000737:chemistry; D006801:Humans; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation / Q000379:methods*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism; D009569:Nitric Oxide / Q000737:chemistry / Q000378:metabolism; D010477:Perfusion; D011138:Polytetrafluoroethylene / Q000737:chemistry; D051381:Rats; D023822:Tissue Engineering
chemical_list: D001672:Biocompatible Materials; D005782:Gels; D009569:Nitric Oxide; D011138:Polytetrafluoroethylene