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2011 | Buch

Myocardial Tissue Engineering

herausgegeben von: Aldo R. Boccaccini, Sian E. Harding

Verlag: Springer Berlin Heidelberg

Buchreihe : Studies in Mechanobiology, Tissue Engineering and Biomaterials

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Über dieses Buch

Myocardial tissue engineering (MTE), a concept that intends to prolong patients’ life after cardiac damage by supporting or restoring heart function, is continuously improving. Common MTE strategies include an engineered ‘vehicle’, which may be a porous scaffold or a dense substrate or patch, made of either natural or synthetic polymeric materials. The function of the substrate is to aid transportation of cells into the diseased region of the heart and support their integration. This book, which contains chapters written by leading experts in MTE, gives a complete analysis of the area and presents the latest advances in the field. The chapters cover all relevant aspects of MTE strategies, including cell sources, specific TE techniques and biomaterials used. Many different cell types have been suggested for cell therapy in the framework of MTE, including autologous bone marrow-derived or cardiac progenitors, as well as embryonic or induced pluripotent stem cells, each having their particular advantages and disadvantages. The book covers a complete range of biomaterials, examining different aspects of their application in MTE, such as biocompatibility with cardiac cells, mechanical capability and compatibility with the mechanical properties of the native myocardium as well as degradation behaviour in vivo and in vitro. Although a great deal of research is being carried out in the field, this book also addresses many questions that still remain unanswered and highlights those areas in which further research efforts are required. The book will also give an insight into clinical trials and possible novel cell sources for cell therapy in MTE.

Inhaltsverzeichnis

Frontmatter
Tissue Engineering for Cardiac Regeneration
Abstract
Tissue engineering is an interdisciplinary field that involves engineering, chemistry, biology and medicine and is emerging in the last decade as a possible approach to regenerate an injured organ by using cells, matrix, biological active molecules and physiologic stimuli. In the cardiovascular field, cardiac tissue engineering (CTE) is suggested as an alternative approach for direct cell transplantation and aims to regenerate an injured myocardial ventricular wall or to repair congenital defects. This chapter will focus on the strategies developed for CTE and in particular on materials and cells used and the advantages that CTE could offers compared to conventional cell therapy.
Roberto Gaetani, Pieter A. F. Doevendans, Elisa Messina, Joost P. G. Sluijter
Inherently Bio-Active Scaffolds: Intelligent Constructs to Model the Stem Cell Niche
Abstract
The oft-abused phrase “genes load the gun, environment pulls the trigger” can be applied to stem cells and stem cell niches as well as to cell–material interfaces. Much is known about cell–material interaction in general, perhaps a little less about how these interactions condition cell phenotype. With the increasing interest in stem cells and, in particular, their applications in tissue regeneration, the regulation of the stem cell microenvironment through modulation of intuitive or smart materials and structures, or what we term IBAS (Inherently Bio-Active Scaffolds) is poised to become a major field of research. Here, we discuss how cardiac regeneration strategies have undergone a gradual shift from the emphasis on biochemical signals and basic biology to one in which the material or scaffold plays a major role in establishing an equilibrium state. From being a constant battle or tug-of-war between the cells and synthetic environments, we conceive IBAS as intuitively responding to the cell’s requirements to instate a sort of equilibrium in the system.
Paolo Di Nardo, Marilena Minieri, Annalisa Tirella, Giancarlo Forte, Arti Ahluwalia
Strategies for Myocardial Tissue Engineering: The Beat Goes On
Abstract
The striving for the ability to build a piece of tissue that resembles the functional features of the heart muscle has been part of the scientific work for almost a century. More than any other organ, the constantly beating pump that drives the blood circulation, has been the focus of spectacular experimental breakthrough reports and subject to significant public interest. Beside the culture-related and religious reasons for the especial public attention that lies upon most medical and scientific work related to the heart, there are numerous matter-of-fact motivations to pay attention to the causes and the cure of heart disease. This work reviews the current strategies for the in vitro or in vivo reconstitution of myocardial tissue, including current concepts or the generation and implementation of extracellular matrix components, discussion of promising sources and culture techniques for the generation of cardiomyocytes or other cell populations necessary for the assembly of a functional myocardium, and finally limitations and perspectives of established myocardial tissue engineering models.
Payam Akhyari, Mareike Barth, Hug Aubin, Artur Lichtenberg
Creating Unique Cell Microenvironments for the Engineering of a Functional Cardiac Patch
Abstract
Tissue engineering is an approach used to create a functional cardiac patch for the purpose of scar support after a myocardial infarct (MI). Cardiac cells, or cells of other sources, are seeded into scaffolds, which provide an artificial biomechanical support until the cells secrete extracellular matrix and regenerate into a functional tissue. In this chapter we describe the creative design of various cell microenvironments, which promote the development of a thick vascularized cardiac patch, ready to face the harsh conditions of the infarcted heart. Among these microenvironments are unique bioreactor systems that increase mass transfer through the developing cardiac tissue at the in vitro engineering stage and the use of various vascularization techniques, including the use of the body as a bioreactor to induce rapid vascularization prior to transplantation on the infarcted heart.
Tal Dvir, Jonathan Leor, Smadar Cohen
Intramyocardial Stem Cell Transplantation Without Tissue Engineered Constructs: The Current Clinical Situation
Abstract
After promising preclinical results, the surgical treatment of chronic ischemic heart disease patients with bone marrow stem cells has been successfully introduced within the last decade in the context of clinical studies and therapy trials. Combining intramyocardial bone marrow stem cell injection with established revascularisation procedures such as bypass surgery seems to offer additional functional benefits compared to standard therapy strategies alone. However, although the safety of intramyocardial stem cell therapy could be demonstrated, the clinical evidence obtained so far is heterogeneous and completion of ongoing Phase III trails is mandatory for conclusive evaluation regarding functional advantages offered by this new therapeutic tool in the cardiac surgeon’s hand. Besides ischemic heart disease also other pathologies—e.g. non-ischemic cardiomyopathy—might form indications for cardiac stem cell therapy, yet further clinical as well as preclinical evidence need to be obtained before adequate therapy strategies might be designed. Delivery and retention of adult stem cells remain limiting factors for treatment.
Peter Donndorf, Gustav Steinhoff
Tissue Engineered Myocardium
Abstract
Myocardial tissue engineering is equally attractive for basic and translational cardiovascular research as it may ultimately provide “realistic” in vitro heart muscle models and therapeutic myocardial substitutes. A prerequisite for successful cardiac muscle engineering is simulation of natural cardiomyogenesis in vitro to yield true myocardial structures with appropriate macro- and micro-morphology as well as function. This requires an assembly of the various cellular and extracellular components of the living heart under so called biomimetic culture conditions. This chapter will give an introduction into different tissue engineering modalities and discuss essential cellular and extracellular components as well as other biomimetic factors, controlling myocardial assembly in vitro. Finally, potential in vitro and in vivo applications such as modeling of heart muscle development, applications in functional genomics and disease modeling, drug development and safety assessment as well as cardiac repair will be reviewed.
Wolfram-Hubertus Zimmermann
Injectable Materials for Myocardial Tissue Engineering
Abstract
Injectable materials have gained recent focus as therapeutic alternatives to treat and prevent heart failure post-myocardial infarction. These materials offer the potential to treat the damaged region of the heart through minimally invasive catheter delivery. A variety of naturally derived and inspired materials, as well as synthetic materials have been explored as potential extracellular matrix replacement scaffolds to prevent a decline in cardiac function and/or improve cell transplant survival. Most recently, decellularized matrices have been suggested, to provide a cardiac-specific biomimetic replacement. This chapter will review the variety of materials that have been explored as injectable therapies for cardiac repair, with a particular focus on decellularized matrices. Additionally, this chapter will review the injection systems currently available, and the design criteria materials must meet for compatibility with minimally invasive catheter delivery.
Jennifer M. Singelyn, Karen L. Christman
Tissue Engineering Approaches for Myocardial Bandage: Focus on Hydrogel Constructs
Abstract
Myocardial tissue engineering ambitions to regenerate, repair or replace damaged cardiac muscle by combining cellular and engineering technologies. Several issues must be addressed before this approach may one day find clinical applications for cardiac disorders such as congenital diseases or ventricular dysfunction following myocardial infarction for example. The chance of the myocardial tissue engineering approach is nevertheless real. Indeed, on the one hand, several clinical studies have recently confirmed the positive effect of stem cell therapy in patients with heart failure. On the other hand, research from several laboratories have demonstrated over the past decade that engineered muscle tissues can be created and successfully applied in models of myocardial injury. Engineering a functional myocardial graft faces with many challenges, and various approaches have been investigated. In the current chapter, we focus our review on hydrogel-based engineered tissues for myocardial application. The literature on injectable and implantable hydrogel constructs is discussed and an overview of our own experience is presented. We emphasize important aspects on development of hydrogel constructs in particular the mechanical and electrical conditioning of the construct as well as smart hydrogels.
Marie Noëlle Giraud, Hendrik Tevaearai
Engineering of Multifunctional Scaffolds for Myocardial Repair Through Nanofunctionalization and Microfabrication of Novel Polymeric Biomaterials
Abstract
In this chapter the authors provide an overview of their research activity in the field of myocardial tissue engineering, focusing on the development of bioactive scaffolds able to guide cardiac tissue formation from dissociated stem cells. The chapter describes the preparation and characterization of new bioartificial polymeric systems, which are blends of natural polymers and a novel thermosensitive and bioresorbable copolymer. The functionalisation of selected polymers using different approaches is presented: surface modification by signalling peptides, application of bioactive molecules release systems and introduction of specific recognition sites by Molecular Imprinting technology. The processing steps to develop highly porous structures, injectable microspheres and innovative scaffolds resembling the cardiac extracellular matrix architecture are further described. Finally, results are presented in the context of the development of scaffolds with multifunctional properties for guiding stem cell plasticity towards myocardial regeneration.
Elisabetta Rosellini, Caterina Cristallini, Niccoletta Barbani, Paolo Giusti
Electrospun Nanocomposites and Stem Cells in Cardiac Tissue Engineering
Abstract
Stem cell therapy is a leading field of research worldwide given its promising potential for recovery or replacement of tissues and organs, especially for the treatment of cardiovascular pathologies. However, despite this enormous experimental effort and the reported positive results in different models, there is no conclusive demonstration of the mechanisms involved in tissue regeneration associated to adult stem cell treatment. This represents one of the major limitations for the clinical translation of stem cell therapy. A real regenerative medicine approach should consider the importance of the extracellular matrix (ECM) and the strong biological signals that it can provide. Connective tissue atmosphere in which cells are embedded exerts a number of actions affecting cells function and supporting their proliferation and differentiation. Polymeric electrospun matrices are among the most promising ECM-mimetic biomaterials, because of their physical structure closely resembling the fibrous proteins in native ECM. Moreover, electrospun materials can be easily functionalized with bioactive molecules providing localized biochemical stimuli to cells seeded therein. The idea of taking advantage of both stem cells plasticity and biomaterials that actively guide and provide the correct sequence of signals to allow ongoing lineage-specific differentiation is an attractive alternative and may represent a promising answer to the treatment limitations of cardiovascular severe diseases.
Jorge A. Genovese, Cristiano Spadaccio, Alberto Rainer, Elvio Covino
Heart Valve Tissue Engineering
Abstract
Extensive research into the structural and functional properties of heart valves shows that they perform sophisticated functions which depend on their unique properties at the tissue, cellular and molecular levels. Furthermore, there is accumulating evidence that these complex functional properties translate into clinically relevant end points to all patients undergoing valve replacement surgery, particularly in children and young adults. Tissue engineering a heart valve offers the potential of replicating these functions and benefits via the production of a ‘living’ valve that resembles the shape and function of the native valve. This chapter will review the biology of heart valves and discuss strategies and advances that have been made towards the goal of producing a living tissue engineered heart valve.
Adrian H. Chester, Magdi H. Yacoub, Patricia M. Taylor
Backmatter
Metadaten
Titel
Myocardial Tissue Engineering
herausgegeben von
Aldo R. Boccaccini
Sian E. Harding
Copyright-Jahr
2011
Verlag
Springer Berlin Heidelberg
Electronic ISBN
978-3-642-18056-9
Print ISBN
978-3-642-18055-2
DOI
https://doi.org/10.1007/978-3-642-18056-9

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