title: Electrical and mechanical stimulation of cardiac cells and tissue constructs.
abstract: The field of cardiac tissue engineering has made significant strides over the last few decades, highlighted by the development of human cell derived constructs that have shown increasing functional maturity over time, particularly using bioreactor systems to stimulate the constructs. However, the functionality of these tissues is still unable to match that of native cardiac tissue and many of the stem-cell derived cardiomyocytes display an immature, fetal like phenotype. In this review, we seek to elucidate the biological underpinnings of both mechanical and electrical signaling, as identified via studies related to cardiac development and those related to an evaluation of cardiac disease progression. Next, we review the different types of bioreactors developed to individually deliver electrical and mechanical stimulation to cardiomyocytes in vitro in both two and three-dimensional tissue platforms. Reactors and culture conditions that promote functional cardiomyogenesis in vitro are also highlighted. We then cover the more recent work in the development of bioreactors that combine electrical and mechanical stimulation in order to mimic the complex signaling environment present in vivo. We conclude by offering our impressions on the important next steps for physiologically relevant mechanical and electrical stimulation of cardiac cells and engineered tissue in vitro.
authors.affiliation: Department of Biomedical Engineering, Tufts University, Medford, MA 02155, United States.
authors.forename: Whitney L
authors.initials: WL
authors.lastname: Stoppel
authors.affiliation: Department of Biomedical Engineering, Tufts University, Medford, MA 02155, United States.
authors.forename: David L
authors.initials: DL
authors.lastname: Kaplan
authors.affiliation: Department of Biomedical Engineering, Tufts University, Medford, MA 02155, United States; Cellular, Molecular and Developmental Biology Program, Sackler School of Graduate Biomedical Sciences, Tufts University School of Medicine, Boston, MA 02111, United States. Electronic address: lauren.black@tufts.edu.
authors.forename: Lauren D
authors.initials: LD
authors.lastname: Black
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D019149:Bioreactors; D002450:Cell Communication; D002478:Cells, Cultured; D004553:Electric Conductivity; D004558:Electric Stimulation; D006321:Heart / Q000502:physiology*; D006801:Humans; D008955:Models, Cardiovascular; D009200:Myocardial Contraction / Q000502:physiology*; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000502:physiology*; D023822:Tissue Engineering / Q000379:methods*
keywords: 3D cardiac tissues; Bioreactors; Cardiac tissue engineering; Electrical stimulation; Electromechanical stimulation; Mechanical stimulation