Kensah g, roa lara a, dahlmann j, et al murine and human pluripotent stem cellderived cardiac bodies form contractile myocardial tissue in vitro. The engineering of 3dimensional 3d heart muscles has undergone exciting progress for the past decade. The american heart association has projected that by 2030, 40% of us adults will be having cardiovascularrelated problems lloydjones et al. Tissue engineering techniques typically make use of constructs, which generally involve 3d polymeric scaffolds in combination with one or more cells types, to form implantable tissue like devices. Cells remain viable even in the depth of the tissue.
In this manner, medium is delivered throughout each cultured scaffold fig. Bioreactor for tissue engineering gene and cell technologies. Multiflow channel bioreactor enables realtime monitoring of. As cardiac tissue is highly specialized and, in contrast to striated muscles such as biceps and quadriceps, not capable of repairing itself, valve replacement is often the only. Bone transplants are widely used in orthopedic, plastic and reconstructive surgery. Bioreactors for cardiac tissue engineering combine novel approaches from biology, engineering, biotechnology, biomechanics, and biomaterials to produce optimized tissue constructs that biomimic. Pdf cardiac tissue engineering using perfusion bioreactor. Effects of mechanical stimulation induced by compression.
Cardiac tissue engineering aims to engineer a contractile patch of physiological thickness to use in surgical repair of diseased heart tissue. Bioreactor systems for tissue engineering cornelia kasper. Review article engineering parameters in bioreactor s design. Electric field stimulation integrated into perfusion bioreactor for cardiac tissue engineering. Development of a novel bioreactor for the mechanical loading. Cardiovascular disease, a set of pathologies that include myocardial infarction mi and heart failure, is the leading cause of death around the. Bioreactor design considerations for extended culture of primary human vascular smooth muscle cells peter s. Since the ultimate aim of a bioreactor is to create a biological product, the engineering parameters, for example, internal and external mass transfer, fluid velocity, shear stress, electrical current distribution, and so forth, are worth to be. A bioreactor refers to any manufactured device or system that supports a biologically active environment. Hydrodynamics and bioprocess considerations in designing bioreactors for cardiac tissue engineering. Ailing teo, athanasios mantalaris and mayasari lim, hydrodynamics and bioprocess considerations in designing bioreactors for cardiac tissue engineering, journal of regenerative medicine and tissue engineering, 10. Cardiac tissue engineering aims at repairing damaged heart muscle and producing human cardiac tissues for application in drug toxicity studies.
Introduction a biomimetic approach to cardiac tissue engineering may be designed to recapitulate any number of aspects of the in vivo environment, including 3dimensional structure andor biochemical cues 1, physical forces. Bioreactors as engineering support to treat cardiac muscle and. This chapter will focus on different perfusion bioreactors that aim at cultivating highly vascularized and functional engineered heart tissues by, e. In a flow perfusion bioreactor, medium is pumped through each scaffold continuously. Download pdf info publication number us20080311650a1. Abstract the limited ability of cardiac muscle to regenerate after. Scars left on the heart vessels following myocardial. Cells, scaffolds, and molecules for myocardial tissue. Current technologies like autologous and allogenic transplantation have several disadvantages making them relatively unsatisfactory, like donor site morbidity, chronic pain, and immunogenicity and risk hazard from infectious disease. Bioreactors in tissue engineering university of oulu. Heart disease, one of the leading causes of death in modern society, has attracted particular attention in the field of tissue engineering. The inability of fully differentiated, loadbearing cardiovascular tissues to in vivo regenerate and the limitations of the current treatment therapies greatly motivate the efforts of cardiovascular tissue engineering to become an effective clinical strategy for injured heart and vessels. Major obstacles to the generation of functional tissues and their widespread clinical use are related to a limited understanding of the regulatory role of specific physicochemical culture parameters on tissue development, and the high. Ex vivo engineering of living tissues is a rapidly developing area with the potential to impact significantly on a widerange of biomedical applications.
The state of the art for creating a completely cellderived vascular graft requires manipulation of the tissue and is very time consuming. Electric field stimulation integrated into perfusion. Tissue engineering offers an attractive alternative involving the development of biological or hybrid substitutes for implantation into the body with the purpose of fostering remodelling and regeneration of diseased tissue. In order to provide a functional cardiac patch, tissue engineering approaches must accurately mimic the structure of native myocardium over several different length scales. Biotechnological advances in cardiac tissue engineering from a bioreactor perspective, in which recapitulation of functional, biochemical, and physiological characteristics of the cardiac tissue. Over time, bioreactors used in tissue engineering have advanced in sophistication to overcome many of the limitations associated with conventional cell and tissue culture methods andor to direct cell function figure 12. In one case, a bioreactor is a vessel in which a chemical process is carried out which involves organisms or biochemically active substances derived from such organisms. Pdf advanced bioreactor with controlled application of. Our overall approach includes physiologic density of cell subpopulations in a 3d setting to enable cell communication and. So far, we have signed with a publicly traded food company not yet to be named, to explore the utility of this bioreactor to grow vegan meat replacement products.
Design of bioreactors for cardiovascular applications. The central hypothesis was that using a tissue engineering system consisting of isolated cardiac cells, polymer scaffolds, and tissue culture bioreactors, we could engineer cardiac muscle mimicking native tissue in structure and function in the presence of appropriate biochemical and physical signals. A pulsatile bioreactor for conditioning of tissueengineered cardiovascular constructs under endoscopic visualization fabian konig 1, trixi hollweck 2, stefan pfeifer 1, bruno reichart 2, erich wintermantel 1, christian hagl 2 and bassil akra 2, 1 chair of medical engineering, technical university munich, boltzmannstrasse 15. Bioreactors are defined as a device used to develop biological processes by closely monitoring controlled environments. A biomimetic approach to cardiac tissue engineering may be designed to recapitulate any number of aspects of the in vivo environment, including 3dimensional structure andor biochemical cues, physical forces electrical andor mechanical. We previously reported that perfusion of engineered cardiac constructs resulted in improved tissue assembly. Design of electrical stimulation bioreactors for cardiac.
Cell seeding, cultivation parameters, and tissue construct characterization rebecca l. The advances in biotechnology, biomechanics, and biomaterials can be used to develop organ models that aim to accurately emulate their natural counterparts. Our primary objective was to evaluate the effect of mechanical stretch on the contractile properties of threedimensional cardiac constructs in vitro. Bioreactorbased bone tissue engineering intechopen.
Cardiac tissue engineering using perfusion bioreactor system article pdf available in nature protocol 34. Abstract electrical stimulation has been shown to improve functional assembly of cardiomyocytes in vitro for cardiac tissue engineering. Bioreactors for tissue engineering by varun chalupadi. Introduction for the use of tissue engineered constructs in vivo, it is essential to examine their functionality and.
Abstract the advances in biotechnology, biomechanics, and biomaterials can be used to develop organ models that aim to accurately emulate. Bioreactors as engineering support to treat cardiac muscle. Cardiac tissue engineering using perfusion bioreactor systems milica radisic, 1 anna marsano, 2 robert maidhof, 2 yadong wang, 3 and gordana vunjaknovakovic 2 1 department of chemical engineering and applied chemistry, institute of biomaterials and biomedical engineering, university of toronto, toronto, ontario, canada. Perfusion bioreactors for prevascularization strategies in. Tissue engineering techniques typically make use of constructs, which generally involve 3d polymeric scaffolds in combination with one or more cells types, to. It is an interdisciplinary field in which the principles of engineering and life science meet each other to generate biological substitutes for creation, preservation or restoration of lost organ functions. Strategies of tissue engineering can be classified as in vitro and in vivo approaches fig. Unlike organ transplantation, tissue engineering offers offtheshelf tissue and organ substitutes. Cardiovascular disease is the leading cause of morbidity and mortality in the western world. In this study, we describe a novel bioreactor system to deliver controlled stretch protocols to bioengineered heart muscle behm constructs. Design of a flow perfusion bioreactor system for bone. In heart valve fabrication, the development of bioreactors for tissue formation under dynamic culture conditions was demonstrated several times 1,8,9. Behms were formed by culturing primary neonatal cardiac myocytes in a fibrin gel.
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. As engineering approaches get ever more sophisticated and bioreactors increasingly complex, cardiac tissue engineering evolves and quality control becomes more prominent. Cardiac tissue engineering by nina tandon submitted to the department of electrical engineering and computer science on august 11, 2006 in partial fulfillment of the requirements for the degree of master of science in electrical engineering abstract a major challenge of tissue engineering is directing cells to establish the. These seeding and culturing bioreactors have been designed for engineering vascular grafts 22 and have recently been used in engineering cartilage 23 and cardiac 24 tissues, and in maintaining. It is generally understood as a process of taking human or animal tissues, isolating cells from the tissues, culturing the isolated cells in a supporting material, i. A novel pulsatile bioreactor for mechanical stimulation of. A flow perfusion bioreactor offers several advantages for culturing scaffolds for tissue engineering. We are in discussion with two other groups for applications in cultured vegan apparel i.
Multiflow channel bioreactor enables realtime monitoring. To engineer bone tissue successfully it may be bene. Engineering skeletal muscle tissue in bioreactor systems. Barash y, dvir t, tandeitnik p, ruvinov e, guterman h, cohen s. Freed,2 gordana vunjaknovakovic2 1department of chemical engineering, massachusetts institute of technology, cambridge.
For this purpose, different kinds of dynamic bioreactorbased cultivation systems have been proposed. This book offers a comprehensive overview of the cardiac tissue engineering strategies, including presenting and discussing the various concepts in use, research directions and applications. Freed,2 gordana vunjaknovakovic2 1department of chemical engineering, massachusetts institute of technology, cambridge, massachusettes. Tissue engineering has emerged as a thriving new field in medical science. Lovati 1 1cell and tissue engineering laboratory, irccs istituto ortopedico galeazzi, via riccardo galeazzi 4, 20161 milan, italy. Bioreactor technology in cardiovascular tissue engineering. Tissue engineering represents one of the major emerging fields in modern b technology. Bioreactor for modulation of cardiac microtissue phenotype by. This chapter outlines the requirements and current designs of bioreactors for the tissue engineering of cardiovascular constructs, such as heart valve and vascular grafts.
In the context of tissue engineering, the term bioreactor was initially used to describe little more than simple mixing of a petri dish. Us11568,727 20040506 20050504 bioreactor for tissue engineering abandoned. A pulsatile bioreactor for conditioning of tissueengineered. Tissue engineering follows the principles of cell transplantation, materials science, and. Vunjaknovakovic nt, am, and gvn are with columbia university, dept. Pdf bioreactors as engineering support to treat cardiac muscle.
Bioreactor for modulation of cardiac microtissue phenotype. Bioreactors are important inevitable part of any tissue engineering te strategy as they aid the construction of threedimensional functional tissues. Pulsatile perfusion bioreactor for cardiac tissue engineering. Cardiac tissue engineering using perfusion bioreactor. A cardiac patch is a functioning piece of laboratorygrown heart tissue that can be used in replacing the patients damaged one before the entire organ has been affected zandonella, 2003. Cardiac tissue engineering by nina tandon submitted to the department of electrical engineering and computer science on august 11, 2006 in partial fulfillment of the requirements for the degree of master of science in electrical engineering abstract a major challenge of tissue engineering is. Development of a novel bioreactor for the mechanical. This approach has been investigated for repairing ligaments and tendons 1, heart valves, bladder 2, small diameter vascular grafts 3, 4 and surgical patches. Cardiac tissue engineering using perfusion bioreactor system. Either the whole valve can be engineered from human cells or a. Design of electrical stimulation bioreactors for cardiac tissue engineering n.
Bioreactors for cardiac tissue engineering request pdf. Cardiac tissue engineering using perfusion bioreactor systems. Bioreactor cultivation for only 4 days under perfusion and continuous electrical stimulus 74. We conclude with recommendations for studies involving carbon electrodes for cardiac tissue engineering. At the centimeter scale, tissue engineering should yield a mechanically stable construct of clinically relevant thickness, comparable to the thickness of the human. Currently, the laboratory is using a bioreactor designed in 2011 that does not currently meet these objectives. Pdf hydrodynamics and bioprocess considerations in designing. Pdf bioreactors as engineering support to treat cardiac. Cardiovascular disease is the number one cause of mortality in north america. Review article engineering parameters in bioreactor s. Advanced bioreactor with controlled application of multidimensional strain for tissue engineering.
It is also already known, that bioreactors support tissue formation of heart muscle in vitro 10,11. We investigated the effects of compression 1 hz, 15% strain combined with fluid shear stress 10. This invention relates to a bioreactor for tissue engineering and a method of operating such a bioreactor. Bioreactors for cardiac tissue engineering harvard university. Independent, controllable stretchperfusion bioreactor. Carrier,1 maria papadaki,2 maria rupnick,3 frederick j. Tissue engineering is a multidisciplinary field that applies basic concepts and techniques of life science and engineering. Cardiac tissue engineering presents a challenge due to the complexity of the muscle tissue and the need for multiple signals to induce tissue regeneration in vitro. These bioreactors are commonly cylindrical, ranging in size from litres. 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. The aim of this chapter is to describe the main issues of bone tissue engineering. The current methods also use the traditional method of growing cells on a flat plate, where they grow and divide naturally with ease.
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