Electrical coupling of isolated cardiomyocyte clusters grown on aligned conductive nanofibrous meshes for their synchronized beating

Hsiao, Chun-Wen; Bai, Meng–Yi; Chang, Yen; Chung, Min‐Fan; Lee, Ting‐Yin; Wu, Cheng‐Tse; Maiti, B. R.; Liao, Zi-Xian; Li, Ren‐Ke; Sung, Hsing‐Wen

doi:10.1016/j.biomaterials.2012.10.065

Cited by 241 publications

(185 citation statements)

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“…12 We have recently reported that isolated cardiomyocytes could grow on aligned composite conductive nanofibers of polyaniline and show synchronized beating. 33 In this study, optical mapping showed that chitosan-PPy-treated hearts had faster transverse conduction velocities along the border zone epicardial surface. This enhanced conduction velocity and repolarization in the peri-infarct regions could facilitate synchronous contraction thereby improving cardiac function.…”

Section: Discussionmentioning

confidence: 54%

A Conductive Polymer Hydrogel Supports Cell Electrical Signaling and Improves Cardiac Function After Implantation into Myocardial Infarct

et al. 2015

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C oronary heart disease is the leading cause of the rising incidence of heart failure worldwide.1 Following myocardial infarction (MI), the limited regenerative potential of the heart causes scar formation in and around the infarction, leading to abnormal electric signal propagation and desynchronized cardiac activation and contraction.2 The lack of electric connection between healthy myocardium and the scar with its islands of intact cardiomyocytes contributes to progressive functional decompensation. Injectable biomaterial has shown promise as an alternative biological treatment option after MI to reduce adverse remodeling and preserve cardiac function.3,4 Among their many advantages, injectable materials can be delivered alone or as a vehicle carrying combination therapies, including cells or growth factors, and may provide mechanical and functional support to the injured heart. Over the past decade, several injectable biomaterials such as collagen, 5,6 alginate, 7 and fibrin 8 have been extensively studied. Organic polymers that conduct electricity (conductive polymers) were first described in 1977, and this discovery was awarded the Nobel prize in 2000.9,10 Conductive polymers are particularly appealing because they exhibit electric properties similar to metals and semiconductors while retaining flexibility, ease of processing, and modifiable conductivity. The electric properties of these materials can be fine-tuned by altering their synthetic processes, including the addition of specific chemical agents.11 Biological applications of conductive polymersBackground-Efficient cardiac function requires synchronous ventricular contraction. After myocardial infarction, the nonconductive nature of scar tissue contributes to ventricular dysfunction by electrically uncoupling viable cardiomyocytes in the infarct region. Injection of a conductive biomaterial polymer that restores impulse propagation could synchronize contraction and restore ventricular function by electrically connecting isolated cardiomyocytes to intact tissue, allowing them to contribute to global heart function. Methods and Results-We created a conductive polymer by grafting pyrrole to the clinically tested biomaterial chitosan to create a polypyrrole (PPy)-chitosan hydrogel. Cyclic voltammetry showed that PPy-chitosan had semiconductive properties lacking in chitosan alone. PPy-chitosan did not reduce cell attachment, metabolism, or proliferation in vitro. Neonatal rat cardiomyocytes plated on PPy-chitosan showed enhanced Ca 2+ signal conduction in comparison with chitosan alone. PPy-chitosan plating also improved electric coupling between skeletal muscles placed 25 mm apart in comparison with chitosan alone, demonstrating that PPy-chitosan can electrically connect contracting cells at a distance. In rats, injection of PPy-chitosan 1 week after myocardial infarction decreased the QRS interval and increased the transverse activation velocity in comparison with saline or chitosan, suggesting improved electric conduction. Optical mapping showed incr...

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Section: Discussionmentioning

confidence: 54%

A Conductive Polymer Hydrogel Supports Cell Electrical Signaling and Improves Cardiac Function After Implantation into Myocardial Infarct

et al. 2015

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“…19 Because of the improvements observed in construct development, electrical stimulation has been used in a number of other studies as a method of developing functional engineered cardiac constructs. [20][21][22] Though both electrical and mechanical stimulation are standard methods of physical stimulation in cardiac construct development, to date, there have been no direct comparisons of the differences between electrical and mechanical stimulation. Attempting to compare published data is also difficult as these studies have been done in different systems with different measures of improvement.…”

Section: Introductionmentioning

confidence: 99%

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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“…One also common method to improve conductivity is the incorporation of conductive biocompatible polymers in the same way as described previously (co-electrospinning). Polyaniline (PANi) and polypyrrole (PPy) are the two most used conductive polymers for coelectrospinning [140][141][142][143] [144]. By using this approach, an electrically active scaffold can be created, which will coordinate the synchronous beating of cultured CMs in the scaffold.…”

Section: Co-electrospinning With Conductive Materialsmentioning

confidence: 99%

“…These materials (PANi and PPy) are compatible and amenable to the electrospinning technology, while their conductivity can be manipulated by the change of the percentage of the conductive polymer in the initial mixture. For example Hsiao et al fabricated nanofibers by coelectrospinning of PANI with PLGA ( figure 7) [140]. The main difficulty here lays in the fact that their chemical composition can be affected by this process, which may change their biological and mechanical properties.…”

Section: Co-electrospinning With Conductive Materialsmentioning

confidence: 99%

Fibers for hearts: A critical review on electrospinning for cardiac tissue engineering

et al. 2017

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Please cite this article as: Kitsara, M., Agbulut, O., Kontziampasis, D., Chen, Y., Menasché, P., Fibers for hearts: A critical review on electrospinning for cardiac tissue engineering, Acta Biomaterialia (2016), doi: http://dx.doi.org/ 10. 1016/j.actbio.2016.11.014 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. AbstractCardiac cell therapy holds a real promise for improving heart function and especially of the chronically failing myocardium. Embedding cells into 3D biodegradable scaffolds may better preserve cell survival and enhance cell engraftment after transplantation, consequently improving cardiac cell therapy compared with direct intramyocardial injection of isolated cells.The primary objective of a scaffold used in tissue engineering is the recreation of the natural 3D environment most suitable for an adequate tissue growth. An important aspect of this commitment is to mimic the fibrillar structure of the extracellular matrix, which provides essential guidance for cell organization, survival, and function. Recent advances in nanotechnology have significantly improved our capacities to mimic the extracellular matrix. Among them, electrospinning is well known for being easy to process and cost effective. Consequently, it is becoming increasingly popular for biomedical applications and it is most definitely the cutting edge technique to make scaffolds that mimic the extracellular matrix for industrial applications.Here, the desirable physico-chemical properties of the electrospun scaffolds for cardiac therapy are described, and polymers are categorized to natural and synthetic. Moreover, the methods used for improving functionalities by providing cells with the necessary chemical cues and a more in vivo-like environment are reported.

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Electrical coupling of isolated cardiomyocyte clusters grown on aligned conductive nanofibrous meshes for their synchronized beating

Cited by 241 publications

References 52 publications

A Conductive Polymer Hydrogel Supports Cell Electrical Signaling and Improves Cardiac Function After Implantation into Myocardial Infarct

A Conductive Polymer Hydrogel Supports Cell Electrical Signaling and Improves Cardiac Function After Implantation into Myocardial Infarct

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

Fibers for hearts: A critical review on electrospinning for cardiac tissue engineering

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