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Su Ryon Shin - One of the best experts on this subject based on the ideXlab platform.
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protein polysaccharide based scaffolds mimicking native extracellular matrix for Cardiac Tissue Engineering applications
Journal of Biomedical Materials Research Part A, 2018Co-Authors: Elisabetta Rosellini, Yu Shrike Zhang, Bianca Migliori, N Barbani, Luigi Lazzeri, Su Ryon Shin, Mehmet R DokmeciAbstract:Tissue Engineering has emerged as a viable approach to treat disease or repair damage in Tissues and organs. One of the key elements for the success of Tissue Engineering is the use of a scaffold serving as artificial extracellular matrix (ECM). The ECM hosts the cells and improves their survival, proliferation, and differentiation, enabling the formation of new Tissue. Here, we propose the development of a class of protein/polysaccharide-based porous scaffolds for use as ECM substitutes in Cardiac Tissue Engineering. Scaffolds based on blends of a protein component, collagen or gelatin, with a polysaccharide component, alginate, were produced by freeze-drying and subsequent ionic and chemical crosslinking. Their morphological, physicochemical, and mechanical properties were determined and compared with those of natural porcine myocardium. We demonstrated that our scaffolds possess highly porous and interconnected structures, and the chemical homogeneity of the natural ECM was well reproduced in both types of scaffolds. Furthermore, the alginate/gelatin scaffolds better mimicked native Tissue in terms of interactions between components and protein secondary structure, and in terms of swelling behavior. The alginate/gelatin scaffolds also show superior mechanical properties for the desired application and support better adhesion, growth, and differentiation of myoblasts under static conditions. The alginate/gelatin scaffolds were subsequently used for culturing neonatal rat cardiomyocytes, where high viability of the resulting Cardiac constructs was observed under dynamic flow culture in a microfluidic bioreactor. We therefore propose our protein/polysaccharide scaffolds as a viable ECM substitute for applications in Cardiac Tissue Engineering. This article is protected by copyright. All rights reserved.
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protein polysaccharide based scaffolds mimicking native extracellular matrix for Cardiac Tissue Engineering applications
Journal of Biomedical Materials Research Part A, 2018Co-Authors: Elisabetta Rosellini, Yu Shrike Zhang, Bianca Migliori, N Barbani, Luigi Lazzeri, Su Ryon Shin, Mehmet R DokmeciAbstract:Tissue Engineering has emerged as a viable approach to treat disease or repair damage in Tissues and organs. One of the key elements for the success of Tissue Engineering is the use of a scaffold serving as artificial extracellular matrix (ECM). The ECM hosts the cells and improves their survival, proliferation, and differentiation, enabling the formation of new Tissue. Here, we propose the development of a class of protein/polysaccharide-based porous scaffolds for use as ECM substitutes in Cardiac Tissue Engineering. Scaffolds based on blends of a protein component, collagen or gelatin, with a polysaccharide component, alginate, were produced by freeze-drying and subsequent ionic and chemical crosslinking. Their morphological, physicochemical, and mechanical properties were determined and compared with those of natural porcine myocardium. We demonstrated that our scaffolds possessed highly porous and interconnected structures, and the chemical homogeneity of the natural ECM was well reproduced in both types of scaffolds. Furthermore, the alginate/gelatin (AG) scaffolds better mimicked the native Tissue in terms of interactions between components and protein secondary structure, and in terms of swelling behavior. The AG scaffolds also showed superior mechanical properties for the desired application and supported better adhesion, growth, and differentiation of myoblasts under static conditions. The AG scaffolds were subsequently used for culturing neonatal rat cardiomyocytes, where high viability of the resulting Cardiac constructs was observed under dynamic flow culture in a microfluidic bioreactor. We therefore propose our protein/polysaccharide scaffolds as a viable ECM substitute for applications in Cardiac Tissue Engineering. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 769-781, 2018.
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reduced graphene oxide gelma hybrid hydrogels as scaffolds for Cardiac Tissue Engineering
Small, 2016Co-Authors: Mohsen Akbari, Su Ryon Shin, Claudio Zihlmann, Pribpandao AssawesAbstract:Biomaterials currently used in Cardiac Tissue Engineering have certain limitations, such as lack of electrical conductivity and appropriate mechanical properties, which are two parameters playing a key role in regulating Cardiac cell behavior. Here, the myocardial Tissue constructs are engineered based on reduced graphene oxide (rGO)-incorporated gelatin methacryloyl (GelMA) hybrid hydrogels. The incorporation of rGO into the GelMA matrix significantly enhances the electrical conductivity and mechanical properties of the material. Moreover, cells cultured on composite rGO-GelMA scaffolds exhibit better biological activities such as cell viability, proliferation, and maturation compared to ones cultured on GelMA hydrogels. Cardiomyocytes show stronger contractility and faster spontaneous beating rate on rGO-GelMA hydrogel sheets compared to those on pristine GelMA hydrogels, as well as GO-GelMA hydrogel sheets with similar mechanical property and particle concentration. Our strategy of integrating rGO within a biocompatible hydrogel is expected to be broadly applicable for future biomaterial designs to improve Tissue Engineering outcomes. The engineered Cardiac Tissue constructs using rGO incorporated hybrid hydrogels can potentially provide high-fidelity Tissue models for drug studies and the investigations of Cardiac Tissue development and/or disease processes in vitro.
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from Cardiac Tissue Engineering to heart on a chip beating challenges
Biomedical Materials, 2015Co-Authors: Yu Shrike Zhang, Su Ryon Shin, Julio Aleman, Andrea Arneri, Simone Bersini, Francesco PirainoAbstract:The heart is one of the most vital organs in the human body, which actively pumps the blood through the vascular network to supply nutrients to as well as to extract wastes from all other organs, maintaining the homeostasis of the biological system. Over the past few decades, tremendous efforts have been exerted in Engineering functional Cardiac Tissues for heart regeneration via biomimetic approaches. More recently, progress has been made toward the transformation of knowledge obtained from Cardiac Tissue Engineering to building physiologically relevant microfluidic human heart models (i.e. heart-on-chips) for applications in drug discovery. The advancement in stem cell technologies further provides the opportunity to create personalized in vitro models from cells derived from patients. Here, starting from heart biology, we review recent advances in Engineering Cardiac Tissues and heart-on-a-chip platforms for their use in heart regeneration and cardiotoxic/cardiotherapeutic drug screening, and then briefly conclude with characterization techniques and personalization potential of the Cardiac models.
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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distilling complexity to advance Cardiac Tissue Engineering
Science Translational Medicine, 2016Co-Authors: Brenda M Ogle, Milica Radisic, Charles E. Murry, Ibrahim J. Domian, Nenad Bursac, Ngan F Huang, Philippe Menasche, Beth L Pruitt, Jianyi Zhang, Wolfram-hubertus ZimmermannAbstract:The promise of Cardiac Tissue Engineering is in the ability to recapitulate in vitro the functional aspects of a healthy heart and disease pathology as well as to design replacement muscle for clinical therapy. Parts of this promise have been realized; others have not. In a meeting of scientists in this field, five central challenges or “big questions” were articulated that, if addressed, could substantially advance the current state of the art in modeling heart disease and realizing heart repair.
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highly elastic and moldable polyester biomaterial for Cardiac Tissue Engineering applications
ACS Biomaterials Science & Engineering, 2016Co-Authors: Locke Davenport Huyer, Miles Montgomery, Yimu Zhao, Genevieve Conant, Anastasia Korolj, Lewis A. Reis, Boyang Zhang, Stasja Drecun, Milica RadisicAbstract:Polyester biomaterials are used in Tissue Engineering as scaffolds for implantation of Tissues developed in vitro. An ideal biodegradable elastomer for Cardiac Tissue Engineering exhibits a relatively low Young’s modulus, with high elongation and tensile strength. Here we describe a novel polyester biomaterial that exhibits improved elastic properties for Cardiac Tissue Engineering applications. We synthesized poly(octamethylene maleate (anhydride) 1,2,4-butanetricarboxylate) (124 polymer) prepolymer gel in a one-step polycondensation reaction. The prepolymer was then molded as desired and exposed to ultraviolet (UV) light to produce a cross-linked elastomer. 124 polymer exhibited highly elastic properties under aqueous conditions that were tunable according to the UV light exposure, monomer composition, and porosity of the cured elastomer. Its elastomeric properties fell within the range of adult heart myocardium, but they could also be optimized for higher elasticity for weaker immature constructs. The ...
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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.
Mehmet R Dokmeci - One of the best experts on this subject based on the ideXlab platform.
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protein polysaccharide based scaffolds mimicking native extracellular matrix for Cardiac Tissue Engineering applications
Journal of Biomedical Materials Research Part A, 2018Co-Authors: Elisabetta Rosellini, Yu Shrike Zhang, Bianca Migliori, N Barbani, Luigi Lazzeri, Su Ryon Shin, Mehmet R DokmeciAbstract:Tissue Engineering has emerged as a viable approach to treat disease or repair damage in Tissues and organs. One of the key elements for the success of Tissue Engineering is the use of a scaffold serving as artificial extracellular matrix (ECM). The ECM hosts the cells and improves their survival, proliferation, and differentiation, enabling the formation of new Tissue. Here, we propose the development of a class of protein/polysaccharide-based porous scaffolds for use as ECM substitutes in Cardiac Tissue Engineering. Scaffolds based on blends of a protein component, collagen or gelatin, with a polysaccharide component, alginate, were produced by freeze-drying and subsequent ionic and chemical crosslinking. Their morphological, physicochemical, and mechanical properties were determined and compared with those of natural porcine myocardium. We demonstrated that our scaffolds possess highly porous and interconnected structures, and the chemical homogeneity of the natural ECM was well reproduced in both types of scaffolds. Furthermore, the alginate/gelatin scaffolds better mimicked native Tissue in terms of interactions between components and protein secondary structure, and in terms of swelling behavior. The alginate/gelatin scaffolds also show superior mechanical properties for the desired application and support better adhesion, growth, and differentiation of myoblasts under static conditions. The alginate/gelatin scaffolds were subsequently used for culturing neonatal rat cardiomyocytes, where high viability of the resulting Cardiac constructs was observed under dynamic flow culture in a microfluidic bioreactor. We therefore propose our protein/polysaccharide scaffolds as a viable ECM substitute for applications in Cardiac Tissue Engineering. This article is protected by copyright. All rights reserved.
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protein polysaccharide based scaffolds mimicking native extracellular matrix for Cardiac Tissue Engineering applications
Journal of Biomedical Materials Research Part A, 2018Co-Authors: Elisabetta Rosellini, Yu Shrike Zhang, Bianca Migliori, N Barbani, Luigi Lazzeri, Su Ryon Shin, Mehmet R DokmeciAbstract:Tissue Engineering has emerged as a viable approach to treat disease or repair damage in Tissues and organs. One of the key elements for the success of Tissue Engineering is the use of a scaffold serving as artificial extracellular matrix (ECM). The ECM hosts the cells and improves their survival, proliferation, and differentiation, enabling the formation of new Tissue. Here, we propose the development of a class of protein/polysaccharide-based porous scaffolds for use as ECM substitutes in Cardiac Tissue Engineering. Scaffolds based on blends of a protein component, collagen or gelatin, with a polysaccharide component, alginate, were produced by freeze-drying and subsequent ionic and chemical crosslinking. Their morphological, physicochemical, and mechanical properties were determined and compared with those of natural porcine myocardium. We demonstrated that our scaffolds possessed highly porous and interconnected structures, and the chemical homogeneity of the natural ECM was well reproduced in both types of scaffolds. Furthermore, the alginate/gelatin (AG) scaffolds better mimicked the native Tissue in terms of interactions between components and protein secondary structure, and in terms of swelling behavior. The AG scaffolds also showed superior mechanical properties for the desired application and supported better adhesion, growth, and differentiation of myoblasts under static conditions. The AG scaffolds were subsequently used for culturing neonatal rat cardiomyocytes, where high viability of the resulting Cardiac constructs was observed under dynamic flow culture in a microfluidic bioreactor. We therefore propose our protein/polysaccharide scaffolds as a viable ECM substitute for applications in Cardiac Tissue Engineering. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 769-781, 2018.
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hydrogels for Cardiac Tissue Engineering
Npg Asia Materials, 2014Co-Authors: Gulden Camciunal, Mehmet R Dokmeci, Nasim Annabi, Ronglih Liao, Ali KhademhosseiniAbstract:Hydrogel-based scaffolds are promising biomaterials to deliver cells and small biomolecules to regenerate the Cardiac muscle. It is anticipated that cell-loaded hydrogels will potentially be able to mend the broken heart.
Gordana Vunjaknovakovic - One of the best experts on this subject based on the ideXlab platform.
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electrically conductive chitosan carbon scaffolds for Cardiac Tissue Engineering
Biomacromolecules, 2014Co-Authors: Ana M Martins, George Eng, Sofia G Caridade, Joao F Mano, Rui L Reis, Gordana VunjaknovakovicAbstract:In this work, carbon nanofibers were used as doping material to develop a highly conductive chitosan-based composite. Scaffolds based on chitosan only and chitosan/carbon composites were prepared by precipitation. Carbon nanofibers were homogeneously dispersed throughout the chitosan matrix, and the composite scaffold was highly porous with fully interconnected pores. Chitosan/carbon scaffolds had an elastic modulus of 28.1 ± 3.3 KPa, similar to that measured for rat myocardium, and excellent electrical properties, with a conductivity of 0.25 ± 0.09 S/m. The scaffolds were seeded with neonatal rat heart cells and cultured for up to 14 days, without electrical stimulation. After 14 days of culture, the scaffold pores throughout the construct volume were filled with cells. The metabolic activity of cells in chitosan/carbon constructs was significantly higher as compared to cells in chitosan scaffolds. The incorporation of carbon nanofibers also led to increased expression of Cardiac-specific genes involved ...
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optimization of electrical stimulation parameters for Cardiac Tissue Engineering
Journal of Tissue Engineering and Regenerative Medicine, 2011Co-Authors: N Tandon, Robert Maidhof, Hyoungshin Park, Anna Marsano, 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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optimization of electrical stimulation parameters for Cardiac Tissue Engineering
Journal of Tissue Engineering and Regenerative Medicine, 2011Co-Authors: N Tandon, Robert Maidhof, Hyoungshin Park, Anna Marsano, 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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electrical stimulation systems for Cardiac Tissue Engineering
Nature Protocols, 2009Co-Authors: N Tandon, Robert Maidhof, Milica Radisic, Anna Marsano, Christopher Cannizzaro, Penhsiu Grace Chao, Gordana VunjaknovakovicAbstract:We describe a protocol for Tissue Engineering of synchronously contractile Cardiac constructs by culturing Cardiac cells with the application of pulsatile electrical fields designed to mimic those present in the native heart. Tissue culture is conducted in a customized chamber built to allow for cultivation of (i) engineered three-dimensional (3D) Cardiac Tissue constructs, (ii) cell monolayers on flat substrates or (iii) cells on patterned substrates. This also allows for analysis of the individual and interactive effects of pulsatile electrical field stimulation and substrate topography on cell differentiation and assembly. The protocol is designed to allow for delivery of predictable electrical field stimuli to cells, monitoring environmental parameters, and assessment of cell and Tissue responses. The duration of the protocol is 5 d for two-dimensional cultures and 10 d for 3D cultures.
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Cardiac Tissue Engineering using perfusion bioreactor systems
Nature Protocols, 2008Co-Authors: Milica Radisic, Robert Maidhof, Anna Marsano, Yadong Wang, Gordana VunjaknovakovicAbstract:This protocol describes Tissue Engineering of synchronously contractile Cardiac constructs by culturing Cardiac cell populations on porous scaffolds (in some cases with an array of channels) and bioreactors with perfusion of culture medium (in some cases supplemented with an oxygen carrier). The overall approach is 'biomimetic' in nature as it tends to provide in vivo-like oxygen supply to cultured cells and thereby overcome inherent limitations of diffusional transport in conventional culture systems. In order to mimic the capillary network, cells are cultured on channeled elastomer scaffolds that are perfused with culture medium that can contain oxygen carriers. The overall protocol takes 2–4 weeks, including assembly of the perfusion systems, preparation of scaffolds, cell seeding and cultivation, and on-line and end-point assessment methods. This model is well suited for a wide range of Cardiac Tissue Engineering applications, including the use of human stem cells, and high-fidelity models for biological research.
Yu Shrike Zhang - One of the best experts on this subject based on the ideXlab platform.
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Bioreactors for Cardiac Tissue Engineering
Advanced healthcare materials, 2018Co-Authors: Jesus Paez-mayorga, Gustavo Hernandez-vargas, Guillermo U. Ruiz-esparza, Hafiz M.n. Iqbal, Xichi Wang, Yu Shrike Zhang, Roberto Parra-saldivar, Ali KhademhosseiniAbstract:The advances in biotechnology, biomechanics, and biomaterials can be used to develop organ models that aim to accurately emulate their natural counterparts. Heart disease, one of the leading causes of death in modern society, has attracted particular attention in the field of Tissue Engineering. To avoid incorrect prognosis of patients suffering from heart disease, or from adverse consequences of classical therapeutic approaches, as well as to address the shortage of heart donors, new solutions are urgently needed. Biotechnological advances in Cardiac Tissue Engineering from a bioreactor perspective, in which recapitulation of functional, biochemical, and physiological characteristics of the Cardiac Tissue can be used to recreate its natural microenvironment, are reviewed. Detailed examples of functional and preclinical applications of engineered Cardiac constructs and the state-of-the-art systems from a bioreactor perspective are provided. Finally, the current trends and future directions of the field for its translation to clinical settings are discussed.
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protein polysaccharide based scaffolds mimicking native extracellular matrix for Cardiac Tissue Engineering applications
Journal of Biomedical Materials Research Part A, 2018Co-Authors: Elisabetta Rosellini, Yu Shrike Zhang, Bianca Migliori, N Barbani, Luigi Lazzeri, Su Ryon Shin, Mehmet R DokmeciAbstract:Tissue Engineering has emerged as a viable approach to treat disease or repair damage in Tissues and organs. One of the key elements for the success of Tissue Engineering is the use of a scaffold serving as artificial extracellular matrix (ECM). The ECM hosts the cells and improves their survival, proliferation, and differentiation, enabling the formation of new Tissue. Here, we propose the development of a class of protein/polysaccharide-based porous scaffolds for use as ECM substitutes in Cardiac Tissue Engineering. Scaffolds based on blends of a protein component, collagen or gelatin, with a polysaccharide component, alginate, were produced by freeze-drying and subsequent ionic and chemical crosslinking. Their morphological, physicochemical, and mechanical properties were determined and compared with those of natural porcine myocardium. We demonstrated that our scaffolds possess highly porous and interconnected structures, and the chemical homogeneity of the natural ECM was well reproduced in both types of scaffolds. Furthermore, the alginate/gelatin scaffolds better mimicked native Tissue in terms of interactions between components and protein secondary structure, and in terms of swelling behavior. The alginate/gelatin scaffolds also show superior mechanical properties for the desired application and support better adhesion, growth, and differentiation of myoblasts under static conditions. The alginate/gelatin scaffolds were subsequently used for culturing neonatal rat cardiomyocytes, where high viability of the resulting Cardiac constructs was observed under dynamic flow culture in a microfluidic bioreactor. We therefore propose our protein/polysaccharide scaffolds as a viable ECM substitute for applications in Cardiac Tissue Engineering. This article is protected by copyright. All rights reserved.
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protein polysaccharide based scaffolds mimicking native extracellular matrix for Cardiac Tissue Engineering applications
Journal of Biomedical Materials Research Part A, 2018Co-Authors: Elisabetta Rosellini, Yu Shrike Zhang, Bianca Migliori, N Barbani, Luigi Lazzeri, Su Ryon Shin, Mehmet R DokmeciAbstract:Tissue Engineering has emerged as a viable approach to treat disease or repair damage in Tissues and organs. One of the key elements for the success of Tissue Engineering is the use of a scaffold serving as artificial extracellular matrix (ECM). The ECM hosts the cells and improves their survival, proliferation, and differentiation, enabling the formation of new Tissue. Here, we propose the development of a class of protein/polysaccharide-based porous scaffolds for use as ECM substitutes in Cardiac Tissue Engineering. Scaffolds based on blends of a protein component, collagen or gelatin, with a polysaccharide component, alginate, were produced by freeze-drying and subsequent ionic and chemical crosslinking. Their morphological, physicochemical, and mechanical properties were determined and compared with those of natural porcine myocardium. We demonstrated that our scaffolds possessed highly porous and interconnected structures, and the chemical homogeneity of the natural ECM was well reproduced in both types of scaffolds. Furthermore, the alginate/gelatin (AG) scaffolds better mimicked the native Tissue in terms of interactions between components and protein secondary structure, and in terms of swelling behavior. The AG scaffolds also showed superior mechanical properties for the desired application and supported better adhesion, growth, and differentiation of myoblasts under static conditions. The AG scaffolds were subsequently used for culturing neonatal rat cardiomyocytes, where high viability of the resulting Cardiac constructs was observed under dynamic flow culture in a microfluidic bioreactor. We therefore propose our protein/polysaccharide scaffolds as a viable ECM substitute for applications in Cardiac Tissue Engineering. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 769-781, 2018.
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from Cardiac Tissue Engineering to heart on a chip beating challenges
Biomedical Materials, 2015Co-Authors: Yu Shrike Zhang, Su Ryon Shin, Julio Aleman, Andrea Arneri, Simone Bersini, Francesco PirainoAbstract:The heart is one of the most vital organs in the human body, which actively pumps the blood through the vascular network to supply nutrients to as well as to extract wastes from all other organs, maintaining the homeostasis of the biological system. Over the past few decades, tremendous efforts have been exerted in Engineering functional Cardiac Tissues for heart regeneration via biomimetic approaches. More recently, progress has been made toward the transformation of knowledge obtained from Cardiac Tissue Engineering to building physiologically relevant microfluidic human heart models (i.e. heart-on-chips) for applications in drug discovery. The advancement in stem cell technologies further provides the opportunity to create personalized in vitro models from cells derived from patients. Here, starting from heart biology, we review recent advances in Engineering Cardiac Tissues and heart-on-a-chip platforms for their use in heart regeneration and cardiotoxic/cardiotherapeutic drug screening, and then briefly conclude with characterization techniques and personalization potential of the Cardiac models.