Optimization of electrical stimulation parameters for cardiac tissue engineering

Tandon, Nina; Marsano, Anna; Maidhof, Robert; Wan, Leo Q.; Park, Hyoungshin; Vunjak-Novakovic, Gordana

doi:10.1002/term.377

Cited by 139 publications

(148 citation statements)

References 31 publications

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“…16 Indeed, our results indicate that biphasic electrical stimulation increased Cx43 and troponin T expression levels when compared with the static conditions. 54 While the degree to which our constructs functionally improved following physical stimulation (38% increase in twitch force) is less than in previously published literature, the magnitude of all of our forces, including the static condition, is significantly higher than what has been reported in those studies. Our results indicate that electrical and mechanical stimulation alone resulted in similar twitch forces, though they affect the construct development in different manners.…”

Section: Fig 8 Growth Signaling Proteins (A)contrasting

confidence: 66%

Mimicking Isovolumic Contraction with Combined Electromechanical Stimulation Improves the Development of Engineered Cardiac Constructs

Morgan

Black²

2014

Tissue Engineering Part A

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Electrical and mechanical stimulation have both been used extensively to improve the function of cardiac engineered tissue as each of these stimuli is present in the physical environment during normal development in vivo. However, to date, there has been no direct comparison between electrical and mechanical stimulation and current published data are difficult to compare due to the different systems used to create the engineered cardiac tissue and the different measures of functionality studied as outcomes. The goals of this study were twofold. First, we sought to directly compare the effects of mechanical and electrical stimulation on engineered cardiac tissue. Second, we aimed to determine the importance of the timing of the two stimuli in relation to each other in combined electromechanical stimulation. We hypothesized that delaying electrical stimulation after the beginning of mechanical stimulation to mimic the biophysical environment present during isovolumic contraction would improve construct function by improving proteins responsible for cell-cell communication and contractility. To test this hypothesis, we created a bioreactor system that would allow us to electromechanically stimulate engineered tissue created from neonatal rat cardiac cells entrapped in fibrin gel during 2 weeks in culture. Contraction force was higher for all stimulation groups as compared with the static controls, with the delayed combined stimulation constructs having the highest forces. Mechanical stimulation alone displayed increased final cell numbers but there were no other differences between electrical and mechanical stimulation alone. Delayed combined stimulation resulted in an increase in SERCA2a and troponin T expression levels, which did not happen with synchronous combined stimulation, indicating that the timing of combined stimulation is important to maximize the beneficial effect. Increases in Akt protein expression levels suggest that the improvements are at least in part induced by hypertrophic growth. In summary, combined electromechanical stimulation can create engineered cardiac tissue with improved functional properties over electrical or mechanical stimulation alone, and the timing of the combined stimulation greatly influences its effects on engineered cardiac tissue.

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Section: Fig 8 Growth Signaling Proteins (A)contrasting

confidence: 66%

Mimicking Isovolumic Contraction with Combined Electromechanical Stimulation Improves the Development of Engineered Cardiac Constructs

Morgan

Black²

2014

Tissue Engineering Part A

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“…One potential explanation was that by offsetting the electrical and mechanical stimulation in the manner that we did, we increased the effective rate of stimulation from 1 Hz to 2 Hz. Increases in the frequency of both mechanical 3 and electrical 35 stimulation have been shown to lead to increased force development. To assess what effect this was having in our system, we added a half offset condition in which the stimulation occurred at half of the frequency of the other groups (total stimulation frequency of 1 Hz, individual stimulation was at 0.5 Hz) to determine if the offset electromechanical stimulation or the increased frequency was the cause of the observed functionality.…”

Section: Offsetting Electrical and Mechanical Stimulationmentioning

confidence: 99%

It's all in the timing: Modeling isovolumic contraction through development and disease with a dynamic dual electromechanical bioreactor system

Morgan

Black

2014

Organogenesis

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This commentary discusses the rationale behind our recently reported work entitled "Mimicking isovolumic contraction with combined electromechanical stimulation improves the development of engineered cardiac constructs," introduces new data supporting our hypothesis, and discusses future applications of our bioreactor system. The ability to stimulate engineered cardiac tissue in a bioreactor system that combines both electrical and mechanical stimulation offers a unique opportunity to simulate the appropriate dynamics between stretch and contraction and model isovolumic contraction in vitro. Our previous study demonstrated that combined electromechanical stimulation that simulated the timing of isovolumic contraction in healthy tissue improved force generation via increased contractile and calcium handling protein expression and improved hypertrophic pathway activation. In new data presented here, we further demonstrate that modification of the timing between electrical and mechanical stimulation to mimic a non-physiological process negatively impacts the functionality of the engineered constructs. We close by exploring the various disease states that have altered timing between the electrical and mechanical stimulation signals as potential future directions for the use of this system.

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“…EIS is an excellent tool for analyzing electrode performance in an electrolyte and can be used to determine presence or absence of irreversible reactions [24][25][26][27]. Impedance Spectroscopy, as the name suggests is the measurement of impedance of an electrical circuit over a range or spectrum of frequencies [70][71][72].…”

Section: Electrochemical Impedance Spectroscopy (Eis)mentioning

confidence: 99%

Development of a thin-film porous-microelectrode array (p-mea) for electrical stimulation of engineered cardiac tissue.

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Optimization of electrical stimulation parameters for cardiac tissue engineering

Cited by 139 publications

References 31 publications

Mimicking Isovolumic Contraction with Combined Electromechanical Stimulation Improves the Development of Engineered Cardiac Constructs

Mimicking Isovolumic Contraction with Combined Electromechanical Stimulation Improves the Development of Engineered Cardiac Constructs

It's all in the timing: Modeling isovolumic contraction through development and disease with a dynamic dual electromechanical bioreactor system

Development of a thin-film porous-microelectrode array (p-mea) for electrical stimulation of engineered cardiac tissue.

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