The Experts below are selected from a list of 1881 Experts worldwide ranked by ideXlab platform
Gordana Vunjaknovakovic - One of the best experts on this subject based on the ideXlab platform.
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optimization of electrical stimulation parameters for cardiac tissue engineering
Journal of Tissue Engineering and Regenerative Medicine, 2011Co-Authors: N. Tandon, Hyoungshin Park, A. Marsano, Robert Maidhof, Gordana VunjaknovakovicAbstract:In vitro application of pulsatile electrical stimulation to neonatal rat cardiomyocytes cultured on polymer scaffolds has been shown to improve the Functional Assembly of cells into contractile engineered cardiac tissues. However, to date, the conditions of electrical stimulation have not been optimized. We have systematically varied the electrode material, amplitude and frequency of stimulation to determine the conditions that are optimal for cardiac tissue engineering. Carbon electrodes, exhibiting the highest charge-injection capacity and producing cardiac tissues with the best structural and contractile properties, were thus used in tissue engineering studies. Engineered cardiac tissues stimulated at 3 V/cm amplitude and 3 Hz frequency had the highest tissue density, the highest concentrations of cardiac troponin-I and connexin-43 and the best-developed contractile behaviour. These findings contribute to defining bioreactor design specifications and electrical stimulation regime for cardiac tissue engineering. Copyright © 2011 John Wiley & Sons, Ltd.
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Functional Assembly of engineered myocardium by electrical stimulation of cardiac myocytes cultured on scaffolds
Proceedings of the National Academy of Sciences of the United States of America, 2004Co-Authors: Milica Radisic, Hyoungshin Park, Lisa E Freed, Helen Shing, Thomas Consi, Frederick J Schoen, Robert Langer, Gordana VunjaknovakovicAbstract:The major challenge of tissue engineering is directing the cells to establish the physiological structure and function of the tissue being replaced across different hierarchical scales. To engineer myocardium, biophysical regulation of the cells needs to recapitulate multiple signals present in the native heart. We hypothesized that excitation–contraction coupling, critical for the development and function of a normal heart, determines the development and function of engineered myocardium. To induce synchronous contractions of cultured cardiac constructs, we applied electrical signals designed to mimic those in the native heart. Over only 8 days in vitro, electrical field stimulation induced cell alignment and coupling, increased the amplitude of synchronous construct contractions by a factor of 7, and resulted in a remarkable level of ultrastructural organization. Development of conductive and contractile properties of cardiac constructs was concurrent, with strong dependence on the initiation and duration of electrical stimulation.
Hyoungshin Park - One of the best experts on this subject based on the ideXlab platform.
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Biomimetic scaffold combined with electrical stimulation and growth factor promotes tissue engineered cardiac development
Experimental Cell Research, 2014Co-Authors: Hyoungshin Park, Benjamin L. Larson, Martin E. Kolewe, Gordana Vunjak-novakovic, Lisa E FreedAbstract:Toward developing biologically sound models for the study of heart regeneration and disease, we cultured heart cells on a biodegradable, microfabricated poly(glycerol sebacate) (PGS) scaffold designed with micro-structural features and anisotropic mechanical properties to promote cardiac-like tissue architecture. Using this biomimetic system, we studied individual and combined effects of supplemental insulin-like growth factor-1 (IGF-1) and electrical stimulation (ES). On culture day 8, all tissue constructs could be paced and expressed the cardiac protein troponin-T. IGF-1 reduced apoptosis, promoted cell-to-cell connectivity, and lowered excitation threshold, an index of electrophysiological activity. ES promoted formation of tissue-like bundles oriented in parallel to the electrical field and a more than ten-fold increase in matrix metalloprotease-2 (MMP-2) gene expression. The combination of IGF-1 and ES increased 2D projection length, an index of overall contraction strength, and enhanced expression of the gap junction protein connexin-43 and sarcomere development. This culture environment, designed to combine cardiac-like scaffold architecture and biomechanics with molecular and biophysical signals, enabled Functional Assembly of engineered heart muscle from dissociated cells and could serve as a template for future studies on the hierarchy of various signaling domains relative to cardiac tissue development. © 2013 Elsevier Inc.
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optimization of electrical stimulation parameters for cardiac tissue engineering
Journal of Tissue Engineering and Regenerative Medicine, 2011Co-Authors: N. Tandon, Hyoungshin Park, A. Marsano, Robert Maidhof, Gordana VunjaknovakovicAbstract:In vitro application of pulsatile electrical stimulation to neonatal rat cardiomyocytes cultured on polymer scaffolds has been shown to improve the Functional Assembly of cells into contractile engineered cardiac tissues. However, to date, the conditions of electrical stimulation have not been optimized. We have systematically varied the electrode material, amplitude and frequency of stimulation to determine the conditions that are optimal for cardiac tissue engineering. Carbon electrodes, exhibiting the highest charge-injection capacity and producing cardiac tissues with the best structural and contractile properties, were thus used in tissue engineering studies. Engineered cardiac tissues stimulated at 3 V/cm amplitude and 3 Hz frequency had the highest tissue density, the highest concentrations of cardiac troponin-I and connexin-43 and the best-developed contractile behaviour. These findings contribute to defining bioreactor design specifications and electrical stimulation regime for cardiac tissue engineering. Copyright © 2011 John Wiley & Sons, Ltd.
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Functional Assembly of engineered myocardium by electrical stimulation of cardiac myocytes cultured on scaffolds
Proceedings of the National Academy of Sciences of the United States of America, 2004Co-Authors: Milica Radisic, Hyoungshin Park, Lisa E Freed, Helen Shing, Thomas Consi, Frederick J Schoen, Robert Langer, Gordana VunjaknovakovicAbstract:The major challenge of tissue engineering is directing the cells to establish the physiological structure and function of the tissue being replaced across different hierarchical scales. To engineer myocardium, biophysical regulation of the cells needs to recapitulate multiple signals present in the native heart. We hypothesized that excitation–contraction coupling, critical for the development and function of a normal heart, determines the development and function of engineered myocardium. To induce synchronous contractions of cultured cardiac constructs, we applied electrical signals designed to mimic those in the native heart. Over only 8 days in vitro, electrical field stimulation induced cell alignment and coupling, increased the amplitude of synchronous construct contractions by a factor of 7, and resulted in a remarkable level of ultrastructural organization. Development of conductive and contractile properties of cardiac constructs was concurrent, with strong dependence on the initiation and duration of electrical stimulation.
Albert J. R. Heck - One of the best experts on this subject based on the ideXlab platform.
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Chaperonin CCT checkpoint function in basal transcription factor TFIID Assembly
Nature Structural & Molecular Biology, 2018Co-Authors: Simona V. Antonova, Laszlo Tora, Elisabeth Scheer, Matthias Haffke, Eleonora Corradini, Mykolas Mikuciunas, Luca Signor, Robert M. Es, Kapil Gupta, Albert J. R. HeckAbstract:A combination of proteomics and structural analyses reveals the Assembly mechanism of transcription factor TFIID in human cells and identifies the chaperonin CCT as a checkpoint in the process. TFIID is a cornerstone of eukaryotic gene regulation. Distinct TFIID complexes with unique subunit compositions exist and several TFIID subunits are shared with other complexes, thereby conveying precise cellular control of subunit allocation and Functional Assembly of this essential transcription factor. However, the molecular mechanisms that underlie the regulation of TFIID remain poorly understood. Here we use quantitative proteomics to examine TFIID submodules and Assembly mechanisms in human cells. Structural and mutational analysis of the cytoplasmic TAF5–TAF6–TAF9 submodule identified novel interactions that are crucial for TFIID integrity and for allocation of TAF9 to TFIID or the Spt-Ada-Gcn5 acetyltransferase (SAGA) co-activator complex. We discover a key checkpoint function for the chaperonin CCT, which specifically associates with nascent TAF5 for subsequent handover to TAF6–TAF9 and ultimate holo-TFIID formation. Our findings illustrate at the molecular level how multisubunit complexes are generated within the cell via mechanisms that involve checkpoint decisions facilitated by a chaperone.
Gordana Vunjak-novakovic - One of the best experts on this subject based on the ideXlab platform.
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Biomimetic scaffold combined with electrical stimulation and growth factor promotes tissue engineered cardiac development
Experimental Cell Research, 2014Co-Authors: Hyoungshin Park, Benjamin L. Larson, Martin E. Kolewe, Gordana Vunjak-novakovic, Lisa E FreedAbstract:Toward developing biologically sound models for the study of heart regeneration and disease, we cultured heart cells on a biodegradable, microfabricated poly(glycerol sebacate) (PGS) scaffold designed with micro-structural features and anisotropic mechanical properties to promote cardiac-like tissue architecture. Using this biomimetic system, we studied individual and combined effects of supplemental insulin-like growth factor-1 (IGF-1) and electrical stimulation (ES). On culture day 8, all tissue constructs could be paced and expressed the cardiac protein troponin-T. IGF-1 reduced apoptosis, promoted cell-to-cell connectivity, and lowered excitation threshold, an index of electrophysiological activity. ES promoted formation of tissue-like bundles oriented in parallel to the electrical field and a more than ten-fold increase in matrix metalloprotease-2 (MMP-2) gene expression. The combination of IGF-1 and ES increased 2D projection length, an index of overall contraction strength, and enhanced expression of the gap junction protein connexin-43 and sarcomere development. This culture environment, designed to combine cardiac-like scaffold architecture and biomechanics with molecular and biophysical signals, enabled Functional Assembly of engineered heart muscle from dissociated cells and could serve as a template for future studies on the hierarchy of various signaling domains relative to cardiac tissue development. © 2013 Elsevier Inc.
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Design of electrical stimulation bioreactors for cardiac tissue engineering
2008 30th Annual International Conference of the IEEE Engineering in Medicine and Biology Society, 2008Co-Authors: N. Tandon, A. Marsano, C. Cannizzaro, J. Voldman, Gordana Vunjak-novakovicAbstract:Electrical stimulation has been shown to improve Functional Assembly of cardiomyocytes in vitro for cardiac tissue engineering. Carbon electrodes were found in past studies to have the best current injection characteristics. The goal of this study was to develop rational experimental design principles for the electrodes and stimulation regime, in particular electrode configuration, electrode ageing, and stimulation amplitude. Carbon rod electrodes were compared via electrochemical impedance spectroscopy (EIS) and we identified a safety range of 0 to 8 V/cm by comparing excitation thresholds and maximum capture rates for neonatal rat cardiomyocytes cultured with electrical stimulation. We conclude with recommendations for studies involving carbon electrodes for cardiac tissue engineering.
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Characterization of Electrical Stimulation Electrodes for Cardiac Tissue Engineering
2006 International Conference of the IEEE Engineering in Medicine and Biology Society, 2006Co-Authors: N. Tandon, C. Cannizzaro, J. Voldman, Elisa Figallo, Gordana Vunjak-novakovicAbstract:Electrical stimulation has been shown to improve Functional Assembly of cardiomyocytes in vitro for cardiac tissue engineering. The goal of this study was to assess the conditions of electrical stimulation with respect to the electrode geometry, material properties and charge-transfer characteristics at the electrode-electrolyte interface. We compared various biocompatible materials, including nanoporous carbon, stainless steel, titanium and titanium nitride, for use in cardiac tissue engineering bioreactors. The faradaic and non-faradaic charge transfer mechanisms were assessed by electrochemical impedance spectroscopy (EIS), studying current injection characteristics, and examining surface properties of electrodes with scanning electron microscopy. Carbon electrodes were found to have the best current injection characteristics. However, these electrodes require careful handling because of their limited mechanical strength. The efficacy of various electrodes for use in 2-D and 3-D cardiac tissue engineering systems with neonatal rat cardiomyocytes is being determined by assessing cell viability, amplitude of contractions, excitation thresholds, maximum capture rate, and tissue morphology
Swarup Bhunia - One of the best experts on this subject based on the ideXlab platform.
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EMBC - Implantable ultrasonic dual Functional Assembly for detection and treatment of anomalous growth
Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and, 2012Co-Authors: Abhishek Basak, Vaishnavi Ranganathan, Seetharam Narasimhan, Swarup BhuniaAbstract:High Intensity Focused Ultrasound (HIFU) is emerging as an accurate, noninvasive method for ablation of certain primary and metastatic tumors. Typically, ablation is performed with an external therapeutic transducer. However, external HIFU treatment suffers from limitations of low therapeutic efficiency for ablation of tumors, deep in internal organs such as liver, kidney and brain. Interstitial HIFU through an internal transducer, implanted locally near the organ of interest, could alleviate some of these limitations. Furthermore, it can be attractive for point-of-care (POC) treatment. In this paper, we propose the design of a dual-Functional implantable Assembly for image-guided HIFU treatment of anomalous growth. It is realized by effective integration of a central HIFU array with two ultrasonic imaging arrays for high-resolution online monitoring and efficient treatment. We explore the design space for the implant and identify the major design parameters including the power requirement. Using a widely used simulation platform, we show that the proposed implant, besides providing a potential POC solution, achieves a better therapeutic performance for certain tumor positions in internal organs, than the extracorporeal HIFU treatment.
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Implantable ultrasonic dual Functional Assembly for detection and treatment of anomalous growth
2012 Annual International Conference of the IEEE Engineering in Medicine and Biology Society, 2012Co-Authors: Abhishek Basak, Vaishnavi Ranganathan, Seetharam Narasimhan, Swarup BhuniaAbstract:High Intensity Focused Ultrasound (HIFU) is emerging as an accurate, noninvasive method for ablation of certain primary and metastatic tumors. Typically, ablation is performed with an external therapeutic transducer. However, external HIFU treatment suffers from limitations of low therapeutic efficiency for ablation of tumors, deep in internal organs such as liver, kidney and brain. Interstitial HIFU through an internal transducer, implanted locally near the organ of interest, could alleviate some of these limitations. Furthermore, it can be attractive for point-of-care (POC) treatment. In this paper, we propose the design of a dual-Functional implantable Assembly for image-guided HIFU treatment of anomalous growth. It is realized by effective integration of a central HIFU array with two ultrasonic imaging arrays for high-resolution online monitoring and efficient treatment. We explore the design space for the implant and identify the major design parameters including the power requirement. Using a widely used simulation platform, we show that the proposed implant, besides providing a potential POC solution, achieves a better therapeutic performance for certain tumor positions in internal organs, than the extracorporeal HIFU treatment.
