Creation of a Bioreactor for the Application of Variable Amplitude Mechanical Stimulation of Fibrin Gel-Based Engineered Cardiac Tissue

Morgan, Kathy Ye; Black, Lauren D.

doi:10.1007/978-1-4939-1047-2_16

Cited by 9 publications

(3 citation statements)

References 14 publications

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“…The design of the reactor control system enables the development of electrical and mechanical stimulation regimes that can mimic both healthy function (isovolumic contraction) as well as characteristic changes in disease. Control of stimulation regimes also enables the integration of construct “exercise” to replicate changes in heart rate [33,34,313,383]. …”

Section: Figmentioning

confidence: 99%

Electrical and mechanical stimulation of cardiac cells and tissue constructs

Stoppel

Kaplan

Black

2016

Advanced Drug Delivery Reviews

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225

190

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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.

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Section: Figmentioning

confidence: 99%

Electrical and mechanical stimulation of cardiac cells and tissue constructs

Stoppel

Kaplan

Black

2016

Advanced Drug Delivery Reviews

Self Cite

225

190

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“…Further studies are required to assess any functional consequences of the altered expression profile. In another study using a novel bioreactor, VS (25% variability) was used in cardiac tissue engineering with a small but significant increase in twitch force compared with static stretch (76). There is only one study that tested the effects of varying the frequency alone (77).…”

Section: Fdm In Other Systemsmentioning

confidence: 99%

Regulatory Roles of Fluctuation-Driven Mechanotransduction in Cell Function

et al. 2016

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Cells in the body are exposed to irregular mechanical stimuli. Here, we review the so-called fluctuation-driven mechanotransduction in which stresses stretching cells vary on a cycle-by-cycle basis. We argue that such mechanotransduction is an emergent network phenomenon and offer several potential mechanisms of how it regulates cell function. Several examples from the vasculature, the lung, and tissue engineering are discussed. We conclude with a list of important open questions.

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“…Annular silicone molds (external diameter = 16 mm, internal diameter = 10 mm, height = 3 mm, with a volume of approximately 400 μL) were manufactured for ECT casting. In each mold, a solution of 10 μL of thrombin (2.5 U/mL final, or 0.1 U/mL thrombin solution per mg fibrinogen, Sigma-Aldrich, United States) ( Hansen et al, 2010 ; Morgan and Black, 2014 ), 23 μL of aprotinin (3000 KIU/mL, Sigma-Aldrich, United States) ( Centola et al, 2013 ), and 116 μL of CaCl 2 (40 mM, Sigma-Aldrich, United States) ( Cholewinski et al, 2009 ) was injected. In parallel, freshly isolated neonatal rat cardiac cells (circa 80% CMs and 20% FBs) were isolated as previously described from 2–3-day-old Sprague Dawley rat hearts ( Radisic et al, 2008 ), according to the Swiss Federal guidelines for animal welfare, and all procedures were approved by the Veterinary Office of the Canton Basel (Basel, Switzerland).…”

Section: Methodsmentioning

confidence: 99%

Bioreactor Platform for Biomimetic Culture and in situ Monitoring of the Mechanical Response of in vitro Engineered Models of Cardiac Tissue

Massai

Pisani

Isu

et al. 2020

Front. Bioeng. Biotechnol.

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In the past two decades, relevant advances have been made in the generation of engineered cardiac constructs to be used as functional in vitro models for cardiac research or drug testing, and with the ultimate but still challenging goal of repairing the damaged myocardium. To support cardiac tissue generation and maturation in vitro , the application of biomimetic physical stimuli within dedicated bioreactors is crucial. In particular, cardiac-like mechanical stimulation has been demonstrated to promote development and maturation of cardiac tissue models. Here, we developed an automated bioreactor platform for tunable cyclic stretch and in situ monitoring of the mechanical response of in vitro engineered cardiac tissues. To demonstrate the bioreactor platform performance and to investigate the effects of cyclic stretch on construct maturation and contractility, we developed 3D annular cardiac tissue models based on neonatal rat cardiac cells embedded in fibrin hydrogel. The constructs were statically pre-cultured for 5 days and then exposed to 4 days of uniaxial cyclic stretch (sinusoidal waveform, 10% strain, 1 Hz) within the bioreactor. Explanatory biological tests showed that cyclic stretch promoted cardiomyocyte alignment, maintenance, and maturation, with enhanced expression of typical mature cardiac markers compared to static controls. Moreover, in situ monitoring showed increasing passive force of the constructs along the dynamic culture. Finally, only the stretched constructs were responsive to external electrical pacing with synchronous and regular contractile activity, further confirming that cyclic stretching was instrumental for their functional maturation. This study shows that the proposed bioreactor platform is a reliable device for cyclic stretch culture and in situ monitoring of the passive mechanical response of the cultured constructs. The innovative feature of acquiring passive force measurements in situ and along the culture allows monitoring the construct maturation trend without interrupting the culture, making the proposed device a powerful tool for in vitro investigation and ultimately production of functional engineered cardiac constructs.

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Creation of a Bioreactor for the Application of Variable Amplitude Mechanical Stimulation of Fibrin Gel-Based Engineered Cardiac Tissue

Cited by 9 publications

References 14 publications

Electrical and mechanical stimulation of cardiac cells and tissue constructs

Electrical and mechanical stimulation of cardiac cells and tissue constructs

Regulatory Roles of Fluctuation-Driven Mechanotransduction in Cell Function

Bioreactor Platform for Biomimetic Culture and in situ Monitoring of the Mechanical Response of in vitro Engineered Models of Cardiac Tissue

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