title: 3D cardiac microtissues encapsulated with the co-culture of cardiomyocytes and cardiac fibroblasts.
abstract: Cardiac tissue engineering has major applications in regenerative medicine, disease modeling and biological studies. Despite the significance, numerous questions still need to be explored to enhance the functionalities of engineered tissue substitutes. In this study, 3D cardiac microtissues are developed through encapsulation of cardiomyocytes and cardiac fibroblasts, as the main cellular constituents of native myocardium. The geometries of the constructs are precisely controlled and assessed for their role on synchronous contraction of the cells. Cardiomyocytes exhibit a native-like phenotype when co-cultured with cardiac fibroblasts as compared to the monoculture condition. Particularly, elongated F-actin fibers with abundance of sarcomeric α-actinin and troponin-I are observed within all layers of the constructs. Higher expressions of connexin-43 and integrin-β1 indicate improved cell-cell and cell-matrix interactions. Amongst co-culture conditions, 2:1 (cardiomyocytes: cardiac fibroblasts) ratio exhibits enhanced functionalities, whereas decreasing the construct size adversely affects the synchronous contraction of the cells. Overall, the study here indicates that the cell-cell ratio and the construct geometry are crucial parameters, which need to be optimized to enhance the functionalities of the engineered tissue substitutes.
authors.affiliation: Harrington Department of Bioengineering, School of Biological and Health Systems Engineering (SBHSE), Arizona State University, Tempe, AZ, 85287, USA.
authors.forename: Harpinder
authors.initials: H
authors.lastname: Saini
authors.affiliation: Harrington Department of Bioengineering, School of Biological and Health Systems Engineering (SBHSE), Arizona State University, Tempe, AZ, 85287, USA.
authors.forename: Ali
authors.initials: A
authors.lastname: Navaei
authors.affiliation: Harrington Department of Bioengineering, School of Biological and Health Systems Engineering (SBHSE), Arizona State University, Tempe, AZ, 85287, USA.
authors.forename: Alison
authors.initials: A
authors.lastname: Van Putten
authors.affiliation: Harrington Department of Bioengineering, School of Biological and Health Systems Engineering (SBHSE), Arizona State University, Tempe, AZ, 85287, USA.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Nikkhah
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000185:Actinin / Q000378:metabolism; D000818:Animals; D018929:Cell Culture Techniques; D002470:Cell Survival; D018920:Coculture Techniques; D018031:Connexin 43 / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry; D019012:Integrin beta1 / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism; D051381:Rats; D023822:Tissue Engineering; D019210:Troponin I / Q000378:metabolism
chemical_list: D018031:Connexin 43; D019012:Integrin beta1; D019210:Troponin I; D000185:Actinin; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate
keywords: cardiac fibroblasts; cardiomyocytes; co-cultures; microtissues