Electric Field Stimulation Integrated into Perfusion Bioreactor for Cardiac Tissue Engineering

Most cardiac diseases are associated with fibrosis. Calcineurin (CaN) is regulated by Ca2+/calmodulin (CaM). The CaN–NFAT (nuclear factor of activated T cell) pathway is involved in the process of cardiac diseases, such as cardiac hypertrophy, but its effect on myocardial fibrosis remains unclear. The present study investigates whether the CaN–NFAT pathway is involved in cardiac fibroblast (CF) proliferation induced by electrical field stimulation (EFS), which recently became a popular treatment for heart failure and cardiac tissue engineering. CF proliferation was evaluated by a cell survival assay (MTT) and cell counts. Myocardial fibrosis was assessed by collagen I and collagen III protein expression. Green fluorescent protein (GFP)-tagged NFAT was used to detect NFAT nuclear translocation. CF proliferation, myocardial fibrosis, CaN activity, and NFAT nuclear translocation were enhanced by EFS. More importantly, these effects were abolished by CaN inhibitors, dominant negative CaN (DN-CaN), and CaN gene silenced with siRNA. Furthermore, buffering intracellular Ca2+ with BAPTA-AM and blocking Ca2+ influx with nifedipine suppressed EFS-induced increase in intracellular Ca2+ and CF proliferation. These results suggested that the CaN–NFAT pathway mediates CF proliferation, and that the CaN–NFAT pathway might be a possible therapeutic target for EFS-induced myocardial fibrosis and cardiac tissue engineering.

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Electric field stimulation for tissue engineering applications

BMC Biomedical Engineering ◽

10.1186/s42490-020-00046-0 ◽

2021 ◽

Vol 3 (1) ◽

Author(s):

Christina N. M. Ryan ◽

Meletios N. Doulgkeroglou ◽

Dimitrios I. Zeugolis

Keyword(s):

Tissue Engineering ◽

Wound Healing ◽

Electric Field ◽

Electric Fields ◽

Cell Types ◽

Field Stimulation ◽

Electric Field Stimulation ◽

Physiological Processes ◽

Different Cell Types

AbstractElectric fields are involved in numerous physiological processes, including directional embryonic development and wound healing following injury. To study these processes in vitro and/or to harness electric field stimulation as a biophysical environmental cue for organised tissue engineering strategies various electric field stimulation systems have been developed. These systems are overall similar in design and have been shown to influence morphology, orientation, migration and phenotype of several different cell types. This review discusses different electric field stimulation setups and their effect on cell response.

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Hysteresis in calcium rhythm patterns during electric field stimulation of cardiac tissue

10.1101/2020.02.29.970780 ◽

2020 ◽

Author(s):

Harold Bien ◽

Salmon Kalkhoran ◽

Emilia Entcheva

Keyword(s):

Electric Field ◽

Cardiac Tissue ◽

Field Stimulation ◽

Electric Field Stimulation ◽

Instability Development ◽

Starting Point ◽

Spatially Extended ◽

Rate Deceleration ◽

Rhythm Pattern ◽

Insight Into

AbstractCardiac tissue subjected to fast pacing via electric field stimulation revealed hysteresis in calcium instability patterns (stimulus:response patterns) beyond departure and return to 1:1 response. The pacing frequency at which the first appearance of instabilities occurred (Fa) was higher than the frequency of ultimate disappearance (Fd) upon rate deceleration. Furthermore, hysteresis was observed in multiple pattern transitions. In the spatially extended system studied here, 2:2 alternans were the preferred starting point (Fa) in calcium instability development, while 2:1 blocks were more common in the return to Fa from higher pacing rates. Recovery of 1:1 patterns was preceded mostly by 2:2 alternans at Fd. In addition to previously reported hysteresis in action potential duration during 1:1 rhythm and alternans magnitude hysteresis (in 2:2 rhythm), our data reveal hysteresis in rhythm pattern transitions not just away from and return to 1:1, but also between different instability patterns, and thus provide insight into the rules of such transitions in electrically stimulated cardiac tissue.

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Pulsatile perfusion bioreactor for cardiac tissue engineering

Biotechnology Progress ◽

10.1002/btpr.11 ◽

2008 ◽

Vol 24 (4) ◽

pp. 907-920 ◽

Cited By ~ 77

Author(s):

Melissa A. Brown ◽

Rohin K. Iyer ◽

Milica Radisic

Keyword(s):

Tissue Engineering ◽

Cardiac Tissue ◽

Cardiac Tissue Engineering ◽

Perfusion Bioreactor ◽

Pulsatile Perfusion

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Micro and Nano-mediated 3D Cardiac Tissue Engineering

10.21236/ada604913 ◽

2010 ◽

Author(s):

Rashid Bashir

Keyword(s):

Tissue Engineering ◽

Cardiac Tissue ◽

Cardiac Tissue Engineering

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Extrinsically Conductive Nanomaterials for Cardiac Tissue Engineering Applications

Micromachines ◽

10.3390/mi12080914 ◽

2021 ◽

Vol 12 (8) ◽

pp. 914

Author(s):

Arsalan Ul Haq ◽

Felicia Carotenuto ◽

Paolo Di Nardo ◽

Roberto Francini ◽

Paolo Prosposito ◽

...

Keyword(s):

Tissue Engineering ◽

Cardiac Tissue ◽

Scar Tissue ◽

Cardiac Tissue Engineering ◽

Assistive Device ◽

Long Run ◽

Fibrotic Scar ◽

Regeneration Capability ◽

Conductive Nanomaterials

Myocardial infarction (MI) is the consequence of coronary artery thrombosis resulting in ischemia and necrosis of the myocardium. As a result, billions of contractile cardiomyocytes are lost with poor innate regeneration capability. This degenerated tissue is replaced by collagen-rich fibrotic scar tissue as the usual body response to quickly repair the injury. The non-conductive nature of this tissue results in arrhythmias and asynchronous beating leading to total heart failure in the long run due to ventricular remodelling. Traditional pharmacological and assistive device approaches have failed to meet the utmost need for tissue regeneration to repair MI injuries. Engineered heart tissues (EHTs) seem promising alternatives, but their non-conductive nature could not resolve problems such as arrhythmias and asynchronous beating for long term in-vivo applications. The ability of nanotechnology to mimic the nano-bioarchitecture of the extracellular matrix and the potential of cardiac tissue engineering to engineer heart-like tissues makes it a unique combination to develop conductive constructs. Biomaterials blended with conductive nanomaterials could yield conductive constructs (referred to as extrinsically conductive). These cell-laden conductive constructs can alleviate cardiac functions when implanted in-vivo. A succinct review of the most promising applications of nanomaterials in cardiac tissue engineering to repair MI injuries is presented with a focus on extrinsically conductive nanomaterials.

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Designing of spider silk proteins for hiPSC-based cardiac tissue engineering

Materials Today Bio ◽

10.1016/j.mtbio.2021.100114 ◽

2021 ◽

pp. 100114

Author(s):

Tilman U. Esser ◽

Vanessa T. Trossmann ◽

Sarah Lentz ◽

Felix B. Engel ◽

Thomas Scheibel

Keyword(s):

Tissue Engineering ◽

Spider Silk ◽

Cardiac Tissue ◽

Cardiac Tissue Engineering ◽

Silk Proteins

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Cardiac Organoids to Model and Heal Heart Failure and Cardiomyopathies

Biomedicines ◽

10.3390/biomedicines9050563 ◽

2021 ◽

Vol 9 (5) ◽

pp. 563

Author(s):

Magali Seguret ◽

Eva Vermersch ◽

Charlène Jouve ◽

Jean-Sébastien Hulot

Keyword(s):

Tissue Engineering ◽

Drug Testing ◽

Cardiac Tissue ◽

Cardiac Tissue Engineering ◽

Cardiac Cells ◽

Cardiac Functions ◽

Different Types ◽

Recent Developments ◽

Human Cardiac Tissue ◽

Key Aspects

Cardiac tissue engineering aims at creating contractile structures that can optimally reproduce the features of human cardiac tissue. These constructs are becoming valuable tools to model some of the cardiac functions, to set preclinical platforms for drug testing, or to alternatively be used as therapies for cardiac repair approaches. Most of the recent developments in cardiac tissue engineering have been made possible by important advances regarding the efficient generation of cardiac cells from pluripotent stem cells and the use of novel biomaterials and microfabrication methods. Different combinations of cells, biomaterials, scaffolds, and geometries are however possible, which results in different types of structures with gradual complexities and abilities to mimic the native cardiac tissue. Here, we intend to cover key aspects of tissue engineering applied to cardiology and the consequent development of cardiac organoids. This review presents various facets of the construction of human cardiac 3D constructs, from the choice of the components to their patterning, the final geometry of generated tissues, and the subsequent readouts and applications to model and treat cardiac diseases.

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