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Milica Radisic - One of the best experts on this subject based on the ideXlab platform.
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hybrid carbon nanotube polymer scaffolds for Cardiac Tissue regeneration
Proceedings of SPIE, 2017Co-Authors: Samad Ahadian, Locke Davenporthuyer, Nathaniel P Smith, Milica RadisicAbstract:Due to insufficient supply of heart transplants and limited regenerative ability of heart Tissues, Cardiac Tissue engineering has emerged to restore or regenerate the structure and function of native Cardiac Tissues. Scaffolds play a major role in fabrication of functional Cardiac Tissues, providing structural support, biodegradation, and cell affinity. However, currently used scaffolds in Cardiac Tissue regeneration tend to lack adequate electrical conductivity and favorable mechanical properties. In response to these concerns, carbon nanotubes (CNTs) have been used to enhance electrical and mechanical properties of scaffolds in Cardiac Tissue engineering. Here, we review different hybrid CNT-biomaterial scaffolds, both natural and synthetic, in Cardiac Tissue regeneration and their fabrication methods. Furthermore, CNT toxicity is also discussed. We further outline future trends in this research area toward using CNTs as a functional nanomaterial in Cardiac Tissue engineering.
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Moldable elastomeric polyester-carbon nanotube scaffolds for Cardiac Tissue engineering.
Acta Biomaterialia, 2016Co-Authors: Samad Ahadian, Nathaniel P Smith, Locke Davenport Huyer, Mehdi Estili, Zhensong Xu, Milica RadisicAbstract:Abstract Polymer biomaterials are used to construct scaffolds in Tissue engineering applications to assist in mechanical support, organization, and maturation of Tissues. Given the flexibility, electrical conductance, and contractility of native Cardiac Tissues, it is desirable that polymeric scaffolds for Cardiac Tissue regeneration exhibit elasticity and high electrical conductivity. Herein, we developed a facile approach to introduce carbon nanotubes (CNTs) into poly(octamethylene maleate (anhydride) 1,2,4-butanetricarboxylate) (124 polymer), and developed an elastomeric scaffold for Cardiac Tissue engineering that provides electrical conductivity and structural integrity to 124 polymer. 124 polymer-CNT materials were developed by first dispersing CNTs in poly(ethylene glycol) dimethyl ether porogen and mixing with 124 prepolymer for molding into shapes and crosslinking under ultraviolet light. 124 polymers with 0.5% and 0.1% CNT content (wt) exhibited improved conductivity against pristine 124 polymer. With increasing the CNT content, surface moduli of hybrid polymers were increased, while their bulk moduli were decreased. Furthermore, increased swelling of hybrid 124 polymer-CNT materials was observed, suggesting their improved structural support in an aqueous environment. Finally, functional characterization of engineered Cardiac Tissues using the 124 polymer-CNT scaffolds demonstrated improved excitation threshold in materials with 0.5% CNT content (3.6 ± 0.8 V/cm) compared to materials with 0% (5.1 ± 0.8 V/cm) and 0.1% (5.0 ± 0.7 V/cm), suggesting greater Tissue maturity. 124 polymer-CNT materials build on the advantages of 124 polymer elastomer to give a versatile biomaterial for Cardiac Tissue engineering applications. Statement of Significance Achieving a high elasticity and a high conductivity in a single Cardiac Tissue engineering material remains a challenge. We report the use of CNTs in making electrically conductive and mechanically strong polymeric scaffolds in Cardiac Tissue regeneration. CNTs were incorporated in elastomeric polymers in a facile and reproducible approach. Polymer-CNT materials were able to construct complicated scaffold structures by injecting the prepolymer into a mold and crosslinking the prepolymer under ultraviolet light. CNTs enhanced electrical conductivity and structural support of elastomeric polymers. Hybrid polymeric scaffolds containing 0.5 wt% CNTs increased the maturation of Cardiac Tissues fabricated on them compared to pure polymeric scaffolds. The Cardiac Tissues on hybrid polymer-CNT scaffolds showed earlier beating than those on pure polymer scaffolds. In the future, fabricated polymer-CNT scaffolds could also be used to fabricate other electro-active Tissues, such neural and skeletal muscle Tissues. In the future, fabricated polymer-CNT scaffolds could also be used to fabricate other electro-active Tissues, such as neural and skeletal muscle Tissues.
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Biomaterials for Cardiac Tissue engineering
Biomedical materials (Bristol England), 2015Co-Authors: Milica RadisicAbstract:The heart is the first organ to start functioning in a human (at three weeks gestation), often before a mother knows she is expecting. It is also the last organ that remains functional, just before death. The first beats are relatively slow and irregular, peaking at 7 weeks gestation at around 3 Hz, more specifically 175 bpm, then decreasing gradually to 140–150 bpm before birth [1]. Subsequently, in the post-natal period, during childhood and into adulthood, the beating rate will further decrease gradually to reach the resting rate of 1 Hz, 60 bpm, on average, in an adult human. The heart will beat approximately 2.5–3.2 billion times and in a life-time [2] of an individual, pumping 175–224 millions of liters of blood throughout the body. This remarkable and truly unique function of the heart is afforded by a sub-set of unique cells in the heart muscle, termed cardiomyocytes, that have an ability to contract in response to electrical stimulation. Heart muscle, the myocardium, is a powerhouse that works to pump the blood throughout the body. The synchronous and integrated action of the myocardial cardiomyocytes is afforded by several structural characteristics: the cells are aligned in parallel with the orientation angle changing through the ventricular wall enabling the ventricle to twist as it contracts, in an attempt to push as much blood out as possible. Cardiomyocytes are intimately connected to one another, directly through gap junctions, enabling electrical impulses to travel around as well as through the cells contributing to the synchronous contractile response. Cardiomyocytes have limited ability to proliferate, as recent studies have conclusively shown that adult humans will replace at most of 50% of the cardiomyocytes they were born with during the average lifetime of 80 years, with an average proliferation rate less than 1% per year [3]. The vision of Cardiac Tissue engineering is to develop in the laboratory, high-fidelity mimics of native human Tissue for modelling of physiology and disease, or ultimately to repair the damaged or impaired heart muscle. For this effort to be successful, one needs to carefully select the source of cardiomyocytes, develop biomaterials that will support the function and assembly of these cells, and often to cultivate these constructs in bioreactors that are focused on providing appropriate electromechanical stimulation. This special section is focused on biomaterials for Cardiac Tissue engineering. In general, the appropriate biomaterial for Cardiac Tissue engineering should be as unique as the heart itself: it should be highly flexible, elastic and capable of enduring millions of contraction cycles, while supporting the seeded cell viability and differentiated phenotype both in vitro and in vivo. The special section combines original research papers and review articles that present recent progress in development of Cardiac Tissue engineering biomaterials. It discusses potential cell sources in original papers [4, 5] and reviews [6]. The use of various hydrogels for cardiovascular Tissue engineering is reviewed [7, 8] and original papers on development of brand new scaffold materials that incorporate architectural complexity of the native myocardium are presented [9, 10]. An approach to increase smooth muscle cell elastogenesis in vitro is presented, an important step towards increasing elasticity during matrix remodelling in engineered Tissues [11]. The featured reviews present recent progress in assembling cells and matrix into functional Tissues by 3D printing [12], and microfabrication for the purposes of personalization, disease modelling and drug discovery [6, 13]. Once the cells are injected or placed with a biomaterial matrix at the desired site in the heart, their fate needs to be tracked in vivo and this special section brings an original paper on in vivo tracking of angiogenic cells transplanted into rodent hearts [14]. Finally, the progress of in vivo pre-clinical studies with engineered Cardiac Tissues on biomaterial matrices are reviewed [15].
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Biomaterial based Cardiac Tissue engineering and its applications
Biomedical materials (Bristol England), 2015Co-Authors: Locke Davenport Huyer, Miles Montgomery, Yimu Zhao, Yun Xiao, Genevieve Conant, Anastasia Korolj, Milica RadisicAbstract:Cardiovascular disease is a leading cause of death worldwide, necessitating the development of effective treatment strategies. A myocardial infarction involves the blockage of a coronary artery leading to depletion of nutrient and oxygen supply to cardiomyocytes and massive cell death in a region of the myocardium. Cardiac Tissue engineering is the growth of functional Cardiac Tissue in vitro on biomaterial scaffolds for regenerative medicine application. This strategy relies on the optimization of the complex relationship between cell networks and biomaterial properties. In this review, we discuss important biomaterial properties for Cardiac Tissue engineering applications, such as elasticity, degradation, and induced host response, and their relationship to engineered Cardiac cell environments. With these properties in mind, we also emphasize in vitro use of Cardiac Tissues for high-throughput drug screening and disease modelling.
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Cardiac Tissue Vascularization: From Angiogenesis to Microfluidic Blood Vessels.
Journal of cardiovascular pharmacology and therapeutics, 2014Co-Authors: Miles Montgomery, Boyang Zhang, Milica RadisicAbstract:Myocardial infarction results from a blockage of a major coronary artery that shuts the delivery of oxygen and nutrients to a region of the myocardium, leading to massive cardiomyocytes death and regression of microvasculature. Growth factor and cell delivery methods have been attempted to revascularize the ischemic myocardium and prevent further cell death. Implantable Cardiac Tissue patches were engineered to directly revascularize as well as remuscularize the affected muscle. However, inadequate vascularization in vitro and in vivo limits the efficacy of these new treatment options. Breakthroughs in Cardiac Tissue vascularization will profoundly impact ischemic heart therapies. In this review, we discuss the full spectrum of vascularization approaches ranging from biological angiogenesis to microfluidic blood vessels as related to Cardiac Tissue engineering.
Paj Peter Hilbers - One of the best experts on this subject based on the ideXlab platform.
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Computer simulations of successful defibrillation in decoupled and non-uniform Cardiac Tissue
Europace, 2005Co-Authors: Nico H.l. Kuijpers, R. H. Keldermann, Theo Arts, Paj Peter HilbersAbstract:Aim The aim of the present study is to investigate the origin and effect of virtual electrode polarization in uniform, decoupled and non-uniform Cardiac Tissue during field stimulation. Methods A discrete bidomain model with active membrane behaviour was used to simulate normal Cardiac Tissue as well as Cardiac Tissue that is decoupled due to fibrosis and gap junction remodelling. Various uniform and non-uniform electric fields were applied to the external domain of uniform, decoupled and non-uniform resting Cardiac Tissue as well as Cardiac Tissue in which spiral waves were induced. Results Field stimulation applied on non-uniform Tissue results in more virtual electrodes compared with uniform Tissue. The spiral waves were terminated in decoupled Tissue, but not in uniform, homogeneous Tissue. By gradually increasing local differences in intracellular conductivities, the amount and spread of virtual electrodes increased and the spiral waves were terminated. Conclusion Fast depolarization of the Tissue after field stimulation may be explained by intracellular decoupling and spatial heterogeneity present in normal and pathological Cardiac Tissue. We demonstrated that termination of spiral waves by means of field stimulation can be achieved when the Tissue is modelled as a non-
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Computer simulations of successful defibrillation in decoupled and non-uniform Cardiac Tissue.
Europace : European pacing arrhythmias and cardiac electrophysiology : journal of the working groups on cardiac pacing arrhythmias and cardiac cellula, 2005Co-Authors: Nico H.l. Kuijpers, R. H. Keldermann, Theo Arts, Paj Peter HilbersAbstract:The aim of the present study is to investigate the origin and effect of virtual electrode polarization in uniform, decoupled and non-uniform Cardiac Tissue during field stimulation. A discrete bidomain model with active membrane behaviour was used to simulate normal Cardiac Tissue as well as Cardiac Tissue that is decoupled due to fibrosis and gap junction remodelling. Various uniform and non-uniform electric fields were applied to the external domain of uniform, decoupled and non-uniform resting Cardiac Tissue as well as Cardiac Tissue in which spiral waves were induced. Field stimulation applied on non-uniform Tissue results in more virtual electrodes compared with uniform Tissue. The spiral waves were terminated in decoupled Tissue, but not in uniform, homogeneous Tissue. By gradually increasing local differences in intracellular conductivities, the amount and spread of virtual electrodes increased and the spiral waves were terminated. Fast depolarization of the Tissue after field stimulation may be explained by intracellular decoupling and spatial heterogeneity present in normal and pathological Cardiac Tissue. We demonstrated that termination of spiral waves by means of field stimulation can be achieved when the Tissue is modelled as a non-uniform, anisotropic bidomain with active membrane behaviour.
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Computer simulations of successful defibrillation in decoupled and non-uniform Cardiac Tissue
EP Europace, 2005Co-Authors: Nico H.l. Kuijpers, R. H. Keldermann, Theo Arts, Paj Peter HilbersAbstract:Abstract Aim The aim of the present study is to investigate the origin and effect of virtual electrode polarization in uniform, decoupled and non-uniform Cardiac Tissue during field stimulation. Methods A discrete bidomain model with active membrane behaviour was used to simulate normal Cardiac Tissue as well as Cardiac Tissue that is decoupled due to fibrosis and gap junction remodelling. Various uniform and non-uniform electric fields were applied to the external domain of uniform, decoupled and non-uniform resting Cardiac Tissue as well as Cardiac Tissue in which spiral waves were induced. Results Field stimulation applied on non-uniform Tissue results in more virtual electrodes compared with uniform Tissue. The spiral waves were terminated in decoupled Tissue, but not in uniform, homogeneous Tissue. By gradually increasing local differences in intracellular conductivities, the amount and spread of virtual electrodes increased and the spiral waves were terminated. Conclusion Fast depolarization of the Tissue after field stimulation may be explained by intracellular decoupling and spatial heterogeneity present in normal and pathological Cardiac Tissue. We demonstrated that termination of spiral waves by means of field stimulation can be achieved when the Tissue is modelled as a non-uniform, anisotropic bidomain with active membrane behaviour.
Nico H.l. Kuijpers - One of the best experts on this subject based on the ideXlab platform.
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Computer simulations of successful defibrillation in decoupled and non-uniform Cardiac Tissue
Europace, 2005Co-Authors: Nico H.l. Kuijpers, R. H. Keldermann, Theo Arts, Paj Peter HilbersAbstract:Aim The aim of the present study is to investigate the origin and effect of virtual electrode polarization in uniform, decoupled and non-uniform Cardiac Tissue during field stimulation. Methods A discrete bidomain model with active membrane behaviour was used to simulate normal Cardiac Tissue as well as Cardiac Tissue that is decoupled due to fibrosis and gap junction remodelling. Various uniform and non-uniform electric fields were applied to the external domain of uniform, decoupled and non-uniform resting Cardiac Tissue as well as Cardiac Tissue in which spiral waves were induced. Results Field stimulation applied on non-uniform Tissue results in more virtual electrodes compared with uniform Tissue. The spiral waves were terminated in decoupled Tissue, but not in uniform, homogeneous Tissue. By gradually increasing local differences in intracellular conductivities, the amount and spread of virtual electrodes increased and the spiral waves were terminated. Conclusion Fast depolarization of the Tissue after field stimulation may be explained by intracellular decoupling and spatial heterogeneity present in normal and pathological Cardiac Tissue. We demonstrated that termination of spiral waves by means of field stimulation can be achieved when the Tissue is modelled as a non-
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Computer simulations of successful defibrillation in decoupled and non-uniform Cardiac Tissue.
Europace : European pacing arrhythmias and cardiac electrophysiology : journal of the working groups on cardiac pacing arrhythmias and cardiac cellula, 2005Co-Authors: Nico H.l. Kuijpers, R. H. Keldermann, Theo Arts, Paj Peter HilbersAbstract:The aim of the present study is to investigate the origin and effect of virtual electrode polarization in uniform, decoupled and non-uniform Cardiac Tissue during field stimulation. A discrete bidomain model with active membrane behaviour was used to simulate normal Cardiac Tissue as well as Cardiac Tissue that is decoupled due to fibrosis and gap junction remodelling. Various uniform and non-uniform electric fields were applied to the external domain of uniform, decoupled and non-uniform resting Cardiac Tissue as well as Cardiac Tissue in which spiral waves were induced. Field stimulation applied on non-uniform Tissue results in more virtual electrodes compared with uniform Tissue. The spiral waves were terminated in decoupled Tissue, but not in uniform, homogeneous Tissue. By gradually increasing local differences in intracellular conductivities, the amount and spread of virtual electrodes increased and the spiral waves were terminated. Fast depolarization of the Tissue after field stimulation may be explained by intracellular decoupling and spatial heterogeneity present in normal and pathological Cardiac Tissue. We demonstrated that termination of spiral waves by means of field stimulation can be achieved when the Tissue is modelled as a non-uniform, anisotropic bidomain with active membrane behaviour.
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Computer simulations of successful defibrillation in decoupled and non-uniform Cardiac Tissue
EP Europace, 2005Co-Authors: Nico H.l. Kuijpers, R. H. Keldermann, Theo Arts, Paj Peter HilbersAbstract:Abstract Aim The aim of the present study is to investigate the origin and effect of virtual electrode polarization in uniform, decoupled and non-uniform Cardiac Tissue during field stimulation. Methods A discrete bidomain model with active membrane behaviour was used to simulate normal Cardiac Tissue as well as Cardiac Tissue that is decoupled due to fibrosis and gap junction remodelling. Various uniform and non-uniform electric fields were applied to the external domain of uniform, decoupled and non-uniform resting Cardiac Tissue as well as Cardiac Tissue in which spiral waves were induced. Results Field stimulation applied on non-uniform Tissue results in more virtual electrodes compared with uniform Tissue. The spiral waves were terminated in decoupled Tissue, but not in uniform, homogeneous Tissue. By gradually increasing local differences in intracellular conductivities, the amount and spread of virtual electrodes increased and the spiral waves were terminated. Conclusion Fast depolarization of the Tissue after field stimulation may be explained by intracellular decoupling and spatial heterogeneity present in normal and pathological Cardiac Tissue. We demonstrated that termination of spiral waves by means of field stimulation can be achieved when the Tissue is modelled as a non-uniform, anisotropic bidomain with active membrane behaviour.
Thomas Eschenhagen - One of the best experts on this subject based on the ideXlab platform.
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Cardiac Tissue engineering: state of the art.
Circulation research, 2014Co-Authors: Marc N. Hirt, Arne Hansen, Thomas EschenhagenAbstract:The engineering of 3-dimensional (3D) heart muscles has undergone exciting progress for the past decade. Profound advances in human stem cell biology and technology, Tissue engineering and material sciences, as well as prevascularization and in vitro assay technologies make the first clinical application of engineered Cardiac Tissues a realistic option and predict that Cardiac Tissue engineering techniques will find widespread use in the preclinical research and drug development in the near future. Tasks that need to be solved for this purpose include standardization of human myocyte production protocols, establishment of simple methods for the in vitro vascularization of 3D constructs and better maturation of myocytes, and, finally, thorough definition of the predictive value of these methods for preclinical safety pharmacology. The present article gives an overview of the present state of the art, bottlenecks, and perspectives of Cardiac Tissue engineering for Cardiac repair and in vitro testing.
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Physiological aspects of Cardiac Tissue engineering
American journal of physiology. Heart and circulatory physiology, 2012Co-Authors: Thomas Eschenhagen, Alexandra Eder, Ingra Vollert, Arne HansenAbstract:Cardiac Tissue engineering aims at repairing the diseased heart and developing Cardiac Tissues for basic research and predictive toxicology applications. Since the first description of engineered heart Tissue 15 years ago, major development steps were directed toward these three goals. Technical innovations led to improved three-dimensional Cardiac Tissue structure and near physiological contractile force development. Automation and standardization allow medium throughput screening. Larger constructs composed of many small engineered heart Tissues or stacked cell sheet Tissues were tested for Cardiac repair and were associated with functional improvements in rats. Whether these approaches can be simply transferred to larger animals or the human patients remains to be tested. The availability of an unrestricted human Cardiac myocyte cell source from human embryonic stem cells or human-induced pluripotent stem cells is a major breakthrough. This review summarizes current Tissue engineering techniques with their strengths and limitations and possible future applications.
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Cardiac Tissue engineering for replacement therapy.
Heart failure reviews, 2003Co-Authors: Wolfram-hubertus Zimmermann, Thomas EschenhagenAbstract:Cell therapy is a new concept to repair diseased organs. For patients with myocardial infarction, heart failure, and congenital heart diseases cell based therapies might represent a potential cure. The field can be subdivided into two principally different approaches: (1) Implantation of isolated cells and (2) implantation of in vitro engineered Tissue constructs. This review will focus on the latter approach. Cardiac Tissue engineering comprises the fields of material sciences and cell biology. In general, scaffold materials such as gelatin, collagen, alginate, or synthetic polymers and Cardiac cells are utilized to reconstitute Tissue-like constructs in vitro. Ideally, these constructs display properties of native myocardium such as coherent contractions, low diastolic tension, and syncytial propagation of action potentials. To be applicable for surgical repair of diseased myocardium engineered Tissue constructs should have the propensity to integrate and remain contractile in vivo. Size and mechanical properties of engineered constructs are critical for surgical repair of large Tissue defects. Successful application of Tissue engineering in men will depend on the utilization of an autologous or non-immunogeneic cell source and scaffold material to avoid life long immunosuppression. This review will give an overview of recent approaches in Cardiac Tissue engineering and its first applications in vivo. We will discuss materials and cell sources for Cardiac Tissue engineering. Further, principle obstacles will be addressed. Cardiac Tissue engineering for replacement therapy has an intriguing perspective, but is in its early days. Its true value remains to be thoroughly evaluated.
James P. Keener - One of the best experts on this subject based on the ideXlab platform.
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Elimination of spiral waves in Cardiac Tissue by multiple electrical shocks.
Physical Review E, 2000Co-Authors: Alexandre V. Panfilov, Stefan C. Müller, Vladimir S. Zykov, James P. KeenerAbstract:We study numerically the elimination of a spiral wave in Cardiac Tissue by application of multiple shocks of external current. To account for the effect of shocks we apply a recently developed theory for the interaction of the external current with Cardiac Tissue. We compare two possible feedback algorithms for timing of the shocks: a "local" feedback algorithm 11 (using an external electrode placed directly on the Tissue) and a "global" feedback algorithm 22 (using the electrocardiogram). Our main results are: application of the external current causes a parametric resonant drift similar to that reported in previous model computations; the ratio of the threshold of elimination of the spiral wave by multiple shocks to the threshold of conventional single shock defibrillation in our model for Cardiac Tissue is about 0.5, while earlier, less realistic models predicted the value about 0.2; we show that an important factor for successful defibrillation is the location of the feedback electrode and the best results are achieved if the feedback electrode or the ECG lead is located at the boundary (or edge) of the Cardiac Tissue; the "local" and the "global" feedback algorithms show similar efficiency.
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A biophysical model for defibrillation of Cardiac Tissue
Biophysical journal, 1996Co-Authors: James P. Keener, Alexander V. PanfilovAbstract:We propose a new model for electrical activity of Cardiac Tissue that incorporates the effects of cellular microstructure. As such, this model provides insight into the mechanism of direct stimulation and defibrillation of Cardiac Tissue after injection of large currents. To illustrate the usefulness of the model, numerical stimulations are used to show the difference between successful and unsuccessful defibrillation of large pieces of Tissue.