title: Silicon nanowire-induced maturation of cardiomyocytes derived from human induced pluripotent stem cells.
abstract: The current inability to derive mature cardiomyocytes from human pluripotent stem cells has been the limiting step for transitioning this powerful technology into clinical therapies. To address this, scaffold-based tissue engineering approaches have been utilized to mimic heart development in vitro and promote maturation of cardiomyocytes derived from human pluripotent stem cells. While scaffolds can provide 3D microenvironments, current scaffolds lack the matched physical/chemical/biological properties of native extracellular environments. On the other hand, scaffold-free, 3D cardiac spheroids (i.e., spherical-shaped microtissues) prepared by seeding cardiomyocytes into agarose microwells were shown to improve cardiac functions. However, cardiomyocytes within the spheroids could not assemble in a controlled manner and led to compromised, unsynchronized contractions. Here, we show, for the first time, that incorporation of a trace amount (i.e., ∼0.004% w/v) of electrically conductive silicon nanowires (e-SiNWs) in otherwise scaffold-free cardiac spheroids can form an electrically conductive network, leading to synchronized and significantly enhanced contraction (i.e., >55% increase in average contraction amplitude), resulting in significantly more advanced cellular structural and contractile maturation.
authors.affiliation: †Bioengineering Department, Clemson University, Clemson, South Carolina 29634, United States.
authors.forename: Yu
authors.initials: Y
authors.lastname: Tan
authors.affiliation: †Bioengineering Department, Clemson University, Clemson, South Carolina 29634, United States.
authors.forename: Dylan
authors.initials: D
authors.lastname: Richards
authors.affiliation: ‡Department of Chemistry, the James Franck Institute and the Institute for Biophysical Dynamics, University of Chicago, Chicago, Illinois 60637, United States.
authors.forename: Ruoyu
authors.initials: R
authors.lastname: Xu
authors.affiliation: †Bioengineering Department, Clemson University, Clemson, South Carolina 29634, United States.
authors.forename: Skylar
authors.initials: S
authors.lastname: Stewart-Clark
authors.affiliation: §Division of Cardiology, Department of Medicine, Gazes Cardiac Research Institute, Medical University of South Carolina, Charleston, South Carolina 29425, United States.
authors.forename: Santhosh Kumar
authors.initials: SK
authors.lastname: Mani
authors.affiliation: †Bioengineering Department, Clemson University, Clemson, South Carolina 29634, United States.|∥Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, South Carolina 29425, United States.
authors.forename: Thomas Keith
authors.initials: TK
authors.lastname: Borg
authors.affiliation: §Division of Cardiology, Department of Medicine, Gazes Cardiac Research Institute, Medical University of South Carolina, Charleston, South Carolina 29425, United States.
authors.forename: Donald R
authors.initials: DR
authors.lastname: Menick
authors.affiliation: ‡Department of Chemistry, the James Franck Institute and the Institute for Biophysical Dynamics, University of Chicago, Chicago, Illinois 60637, United States.
authors.forename: Bozhi
authors.initials: B
authors.lastname: Tian
authors.affiliation: †Bioengineering Department, Clemson University, Clemson, South Carolina 29634, United States.|∥Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, South Carolina 29425, United States.
authors.forename: Ying
authors.initials: Y
authors.lastname: Mei
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects*; D006321:Heart / Q000254:growth & development*; D006801:Humans; D066298:In Vitro Techniques; D057026:Induced Pluripotent Stem Cells / Q000187:drug effects*; D032383:Myocytes, Cardiac / Q000187:drug effects*; D053770:Nanowires / Q000008:administration & dosage; D012825:Silicon / Q000008:administration & dosage; D023822:Tissue Engineering / Q000379:methods; D054457:Tissue Scaffolds / Q000737:chemistry
chemical_list: D012825:Silicon
keywords: cardiac spheroids; cardiomyocytes; human induced pluripotent stem cells; maturation; silicon nanowires
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