title: Scaffold Free Bio-orthogonal Assembly of 3-Dimensional Cardiac Tissue via Cell Surface Engineering.
abstract: There has been tremendous interest in constructing in vitro cardiac tissue for a range of fundamental studies of cardiac development and disease and as a commercial system to evaluate therapeutic drug discovery prioritization and toxicity. Although there has been progress towards studying 2-dimensional cardiac function in vitro, there remain challenging obstacles to generate rapid and efficient scaffold-free 3-dimensional multiple cell type co-culture cardiac tissue models. Herein, we develop a programmed rapid self-assembly strategy to induce specific and stable cell-cell contacts among multiple cell types found in heart tissue to generate 3D tissues through cell-surface engineering based on liposome delivery and fusion to display bio-orthogonal functional groups from cell membranes. We generate, for the first time, a scaffold free and stable self assembled 3 cell line co-culture 3D cardiac tissue model by assembling cardiomyocytes, endothelial cells and cardiac fibroblast cells via a rapid inter-cell click ligation process. We compare and analyze the function of the 3D cardiac tissue chips with 2D co-culture monolayers by assessing cardiac specific markers, electromechanical cell coupling, beating rates and evaluating drug toxicity.
authors.affiliation: Department of Chemistry and Biology, York University, Toronto, M3J 1P3, Canada.
authors.forename: Dmitry
authors.initials: D
authors.lastname: Rogozhnikov
authors.affiliation: Department of Chemistry and Biology, York University, Toronto, M3J 1P3, Canada.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: O'Brien
authors.affiliation: Department of Chemistry and Biology, York University, Toronto, M3J 1P3, Canada.
authors.forename: Sina
authors.initials: S
authors.lastname: Elahipanah
authors.affiliation: Department of Chemistry and Biology, York University, Toronto, M3J 1P3, Canada.|OrganoLinX Inc. Toronto, Canada.
authors.forename: Muhammad N
authors.initials: MN
authors.lastname: Yousaf
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D023822:Tissue Engineering