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A cutting-edge look at the application of micro and nanotechnologies in regenerative medicine
The area at the interface of micro/nanotechnology and stem cells/tissue engineering has seen an explosion of activity in recent years. This book provides a much-needed overview of these exciting developments, covering all aspects of micro and nanotechnologies, from the fundamental principles to the latest research to applications in regenerative medicine.
Written and edited by the top researchers in the field, Micro and Nanotechnologies in Engineering Stem Cells and Tissues describes advances in material systems along with current techniques available for cell, tissue, and organ studies. Readers will gain tremendous insight into the state of the art of stem cells and tissue engineering, and learn how to use the technology in their own research or clinical trials. Coverage includes:
Unrivaled among books of this kind, Micro and Nanotechnologies in Engineering Stem Cells and Tissues is the ultimate forward-looking reference for researchers in numerous disciplines, from engineering and materials science to biomedicine, and for anyone wishing to understand the trends in this transformative field.
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Seitenzahl: 601
Veröffentlichungsjahr: 2013
Contents
Cover
Series Page
Title Page
Copyright
Preface
Contributors
Chapter 1: Stem Cells and Nanotechnology in Tissue Engineering and Regenerative Medicine
1.1 A Brief History of Tissue Engineering and Regenerative Medicine
1.2 Introduction to Stem Cells
1.3 Tissue Engineering and Regenerative Medicine Strategies
1.4 Nanotechnology in Regenerative Medicine and Tissue Engineering
1.5 Conclusions
Acknowledgments
References
Chapter 2: Nanofiber Technology for Controlling Stem Cell Functions and Tissue Engineering
2.1 Introduction
2.2 Fabrication of Nanofibrous Scaffolds by Electrospinning
2.3 Stem Cells: Type, Origin, and Functionality
2.4 Stem Cell–Nanofiber Interactions in Regenerative Medicine and Tissue Engineering
2.5 Conclusions
Acknowledgments
References
Chapter 3: Micro- and Nanoengineering Approaches to Developing Gradient Biomaterials Suitable for Interface Tissue Engineering
3.1 Introduction
3.2 Classification of Gradient Biomaterials
3.3 Micro- and Nanoengineering Techniques for Fabricating Gradient Biomaterials
3.4 Conclusions
Acknowledgments
References
Chapter 4: Microengineered Polymer- and Ceramic-Based Biomaterial Scaffolds: A Topical Review on Design, Processing, and Biocompatibility Properties
4.1 Introduction
4.2 Dense Hydroxyapatite versus Porous Hydroxyapatite Scaffold
4.3 Property Requirement of Porous Scaffold
4.4 Design Criteria and Critical Issues With Porous Scaffolds for Bone Tissue Engineering
4.5 An Exculpation of Porous Scaffolds
4.6 Overview of Various Processing Techniques of Porous Scaffold
4.7 Overview of Physicomechanical Properties Evaluation of Porous Scaffold
4.8 Overview of Biocompatibility Properties: Evaluation of Porous Scaffolds
4.9 Outstanding Issues
4.10 Conclusions
Acknowledgment
References
Chapter 5: Synthetic Enroutes to Engineer Electrospun Scaffolds for Stem Cells and Tissue Regeneration
5.1 Introduction
5.2 Synthetic Enroutes
5.3 Novel Nanofibrous Strategies for Stem Cell Regeneration and Differentiation
5.4 Conclusions
Acknowledgment
References
Chapter 6: Integrating Top-Down and Bottom-Up Scaffolding Tissue Engineering Approach for Bone Regeneration
6.1 Introduction
6.2 Clinic Needs in Bone Regeneration Fields
6.3 Bone Regeneration Strategies and Techniques
6.4 Future Direction and Concluding Remarks
References
Chapter 7: Characterization of The Adhesive Interactions Between Cells and Biomaterials
7.1 Introduction
7.2 Adhesion Receptors in Native Tissue
7.3 Optimization of Cellular Adhesion Through Biomaterial Modification
7.4 Measurement of Cell Adhesion
7.5 Conclusions
Acknowledgments
Disclaimer
References
Chapter 8: Microfluidic Formation of Cell-Laden Hydrogel Modules For Tissue Engineering
8.1 Introduction
8.2 Cell-Laden Hydrogel Modules
8.3 Cell Assay Systems Using Microfluidic Devices
8.4 Implantable Applications
8.5 Tissue Engineering
8.6 Summary
References
Chapter 9: Micro- and Nanospheres for Tissue Engineering
9.1 Introduction
9.2 Materials Classification of Micro- and Nanospheres
9.3 Applications of Micro- and Nanospheres in Tissue Engineering
9.4 Conclusions
Acknowledgments
References
Chapter 10: Micro- and Nanotechnologies To Engineer Bone Regeneration
10.1 Introduction
10.2 Nano-Hydroxyapatite Reinforced Scaffolds
10.3 Biodegradable Polymeric Scaffolds and Nanocomposites
10.4 Silk Fibers and Scaffolds
10.5 Summary
Acknowledgments
References
Chapter 11: Micro- and Nanotechnology for Vascular Tissue Engineering
11.1 Introduction
11.2 Conventional Vascular Grafts
11.3 Tissue-Engineered Vascular Grafts
11.4 Micro- and Nanotopography in Vascular Tissue Engineering
11.5 Micro- and Nanofibrous Scaffolds in Vascular Tissue Engineering
11.6 Microvascular Tissue Engineering
11.7 Conclusions
References
Chapter 12: Application of Stem Cells in Ischemic Heart Disease
12.1 Introduction
12.2 Adult Skeletal Myoblast Cells
12.3 Adult Bone Marrow–Derived Stem Cells
12.4 Type of Stem Cells Used to Treat Cardiac Diseases
12.5 Application
12.6 Other Developing Technologies in Cell Engineering
Acknowledgments
References
Index
IEEE Press Series in Biomedical Engineering
Copyright © 2013 by The Institute of Electrical and Electronics Engineers, Inc.
Published by John Wiley & Sons, Inc., Hoboken, New Jersey. All rights reserved.
Published simultaneously in Canada.
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Library of Congress Cataloging-in-Publication Data:
Micro and nanotechnologies in engineering stem cells and tissues / edited by Murugan Ramalingam ... [et al.].
p. ; cm.
Includes bibliographical references.
ISBN 978-1-118-14042-0 (cloth)
I. Ramalingam, Murugan. II. Institute of Electrical and Electronics Engineers.
[DNLM: 1. Cell Engineering–methods. 2. Stem Cells–physiology. 3. Microtechnology–methods. 4. Nanotechnology–methods. 5. Tissue Engineering–methods. QU 325]
612.6’4018–dc23
2012039996
Preface
More than a million people worldwide are in need of an organ transplant while only 100,000 transplants are performed each year. More than 100,000 Americans need a transplant each year but only 25,000 transplants are performed. Tissue engineering has become increasingly important as an unlimited source of bioengineered tissues to replace diseased organs. Tissue engineering attempts to build body parts by assembling from the basic components of biological tissues, namely, the matrix, cells, and tissue morphogenetic growth factors. As tissue-specific cells are limited in quantity, stem cells with their ability for self-renewal and pluripotency are becoming increasingly important as a cell source in regenerative medicine. These cell sources include but are not limited to bone marrow–derived stromal cells and hematopoietic cells, umbilical cord–derived stem cells, and induced pluripotent stem cells. Top-down approaches utilizing porous scaffolds with random or well-defined pore structures, seeded with cells and growth factors, have been used, in some cases successfully, as cellular constructs in the clinically relevant length scale in regenerative medicine. However, top-down approaches cannot recreate the intricate structural characteristics of native tissues at multiple nano- and microscales, leading to the formation of less than optimal composition and distribution of the extracellular matrix. It should be emphasized that the hierarchical organization of native biological tissues is optimized by evolution to balance strength, cell–cell and cell–matrix interactions, growth factor presentation, and transport of nutrients. Consequently, bottom-up approaches to build a single modular unit to mimic the structural features of native tissues and to serve as a building block for assembly to a larger tissue scale have received more attention in recent years. The processes of cell adhesion, migration, differentiation, extracellular matrix formation, and cell maturation depend on interactions at multiple length scales between the cell surface receptors and their corresponding ligands in the matrix. The success of engineered tissues as an unlimited source for replacement of damaged organs depends on our depth of understanding of those interactions and our ability to mimic those interactions using enabling nano- and microscale technologies and to build modular scalable units for implantation. This book provides an overview of enabling micro- and nanoscale technologies in designing novel materials to elucidate the complex cell–cell and cell–matrix interactions, leading to engineered stem cells and tissues for applications in regenerative medicine. The editors, Murugan Ramalingam, Esmaiel Jabbari, Seeram Ramakrishna, and Ali Khademhosseini, thank the authors for their contribution to this timely book.
Murugan Ramalingam
Centre for Stem Cell Research, India
Esmaiel Jabbari
University of South Carolina, USA
Seeram Ramakrishna
National University of Singapore, Singapore
Ali Khademhosseini
Harvard University, USA
Contributors
Samad Ahadian, WPI-Advanced Institute for Materials Research (WPI-AIMR), Tohoku University, Sendai, Japan
Bikramjit Basu, Laboratory for Biomaterials, Materials Research Center, Indian Institute of Science, Bangalore, India
Allison C. Bean, Center for Cellular and Molecular Engineering, Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
Kimberly M. Ferlin, Fischell Department of Bioengineering, University of Maryland, College Park, MD, USA; U.S. Food and Drug Administration, Center for Devices and Radiological Health, Silver Spring, MD, USA
John P. Fisher, Fischell Department of Bioengineering, University of Maryland, College Park, MD, USA
Esmaiel Jabbari, Chemical Engineering, University of South Carolina, SC, USA
John A. Jansen, Department of Biomaterials, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands
Yunqing Kang, Orthopedic Surgery, Stanford University, CA, USA
David S. Kaplan, U.S. Food and Drug Administration, Center for Devices and Radiological Health, Silver Spring, MD, USA
Ali Khademhosseini, WPI-Advanced Institute for Materials Research (WPI-AIMR), Tohoku University, Sendai, Japan; Center for Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA, USA; Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA, USA
Gaurav Lalwani, Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY, USA
Sander C.G. Leeuwenburgh, Department of Biomaterials, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands
Yubao Li, Research Center for Nano-Biomaterials, Analytical and Testing Center, Sichuan University, Chengdu, P.R. China
Yukiko T. Matsunaga, Institute of Industrial Science (IIS), The University of Tokyo, Japan; PRESTO, JST, Japan
Yuya Morimoto, Institute of Industrial Science (IIS), The University of Tokyo, Japan; Takeuchi Biohybrid Innovation Project, ERATO, JST, Japan
Shayanti Mukherjee, Division of Bioengineering, National University of Singapore, Singapore; HEM Laboratory, Nanoscience and Nanotechnology Initiative, Faculty of Engineering, National University of Singapore, Singapore
Serge Ostrovidov, WPI-Advanced Institute for Materials Research (WPI-AIMR), Tohoku University, Sendai, Japan
Molamma P Prabhakaran, HEM Laboratory, Nanoscience and Nanotechnology Initiative, Faculty of Engineering, National University of Singapore, Singapore
Michael Raghunath, Division of Bioengineering, National University of Singapore, Singapore; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
Seeram Ramakrishna, HEM Laboratory, Nanoscience and Nanotechnology Initiative, Faculty of Engineering, National University of Singapore, Singapore; Department of Mechanical Engineering, National University of Singapore, Singapore; Institute of Materials Research and Engineering, a-star, Singapore
Murugan Ramalingam, Centre for Stem Cell Research (CSCR), (A unit of Institute for Stem Cell Biology and Regenerative Medicine, Bengaluru) Christian Medical College Campus, Vellore, India; Institut National de la Santé Et de la Recherche Médicale UMR977, Faculté de Chirurgie Dentaire, Université de Strasbourg, Strasbourg, France; WPI-Advanced Institute for Materials Research (WPI-AIMR), Tohoku University, Sendai, Japan
Jason Rashkow, Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY, USA
Rajeswari Ravichandran, HEM Laboratory, Nanoscience and Nanotechnology Initiative, Faculty of Engineering, National University of Singapore, Singapore; Department of Mechanical Engineering, National University of Singapore, Singapore
A. Sai Ravi Shankar, Department of Cardiology, Narayana Medical College Hospital, Nellore, Andhra Pradesh, India
Azadeh Seidi, Technology Center, Okinawa Institute of Science and Technology, Onna-son, Okinawa, Japan
Balaji Sitharaman, Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY, USA
Radhakrishnan Sridhar, HEM Laboratory, Nanoscience and Nanotechnology Initiative, Faculty of Engineering, National University of Singapore, Singapore
Ryan S. Stowers, Laboratory for Cardiovascular Tissue Engineering, Department of Biomedical Engineering, University of Texas at Austin, Austin, TX, USA
Gangapatnam Subrahmanyam, Department of Cardiology, Narayana Medical College Hospital, Nellore, Andhra Pradesh, India
Laura J. Suggs, Laboratory for Cardiovascular Tissue Engineering, Department of Biomedical Engineering, University of Texas at Austin, Austin, TX, USA
Shoji Takeuchi, Institute of Industrial Science (IIS), The University of Tokyo, Japan; Takeuchi Biohybrid Innovation Project, ERATO, JST, Japan
Yahfi Talukdar, Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY, USA
Garima Tripathi, Laboratory for Biomaterials, Department of Material Science and Engineering, Indian Institute of Technology, Kanpur, India
Rocky S. Tuan, Center for Cellular and Molecular Engineering, Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
Jayarama Reddy Venugopal, HEM Laboratory, Nanoscience and Nanotechnology Initiative, Faculty of Engineering, National University of Singapore, Singapore
Huanan Wang, Department of Biomaterials, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands; Research Center for Nano-Biomaterials, Analytical and Testing Center, Sichuan University, Chengdu, P.R. China
Yunzhi Yang, Orthopedic Surgery, Stanford University, CA, USA
1
Stem Cells and Nanotechnology in Tissue Engineering and Regenerative Medicine
Allison C. Bean and Rocky S. Tuan
Center for Cellular and Molecular Engineering, Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
Awareness of the natural regenerative capabilities of the human body dates back to ancient times. In Greek mythology, when Prometheus stole fire from the gods and gave it to the mortals, Zeus punished him by tying him to a rock and having an eagle peck away his liver, only to have it regrow and be eaten again the following day. Although the liver has significant natural regenerative capacity that seems to have been apparent for many ages, many other organs have a very limited ability to regrow after damage or removal. These limitations have spurred the development of regenerative approaches in the history of modern medicine, as clinicians and scientists continuously attempt to overcome the body's natural limitations.
The birth of whole-organ transplantation techniques has paved the way for modern developments in regenerative medicine and tissue engineering. Alexis Carrel, winner of the Nobel Prize in Physiology or Medicine in 1912 and the father of whole-organ transplant, was the first to develop a successful technique for end-to-end arteriovenous anastomosis in transplantation. In the 1930s, assisted by Charles Lindbergh, he developed a “perfusion pump” that allowed organs to be maintained outside the body during transplantation, a concept that has been more recently used in bioreactors for tissue engineering studies.1,2
The limitations of organ transplant because of immune reaction were recognized early. Gibson and Medawar found that application of a second skin allograft from the same donor resulted in faster rejection than the first, suggesting that the response may be immunologic.3 Additional studies in dogs showed that allografts produced a mononuclear reaction to the transplanted organ.4 Thus, to avoid the immune response, the first successful kidney transplant was performed in 1954 between identical twins.5 It was not until the development of immunosuppressive drugs that transplantation from genetically different donors became feasible. Many advances have been made in the field of organ transplantation, including the development of immunomodulating therapies and significant reductions in the number of immunosuppressive drugs necessary after transplantation.6,7 However, limitations because of organ or tissue availability and the continual need for chronic immunosuppression remain and have left physicians and scientists looking for a new approach that mitigates these issues. These efforts have resulted in the popularization of the fields of tissue engineering and regenerative medicine.
A succinct definition of regenerative medicine has been provided by Mason et al., stating that “regenerative medicine replaces or regenerates human cells, tissue or organs, to restore or establish normal function.”8 This broad definition can include the use of cell-based therapy, gene therapy, nonbiological devices, and tissue engineering strategies. Organ transplantation falls short in this definition because completely normal function is not possible given the need for continuous immune suppression.
Although the terms tissue engineering and regenerative medicine are sometimes used interchangeably, it is important to understand that tissue engineering falls under the umbrella of the regenerative medicine field but is not all encompassing. As defined by Langer and Vacanti, tissue engineering is “an interdisciplinary field of research that applies the principles of engineering and the life sciences towards the development of biological substitutes that restore, maintain, or improve tissue function.”9 More specifically, tissue engineering uses a combination of cells, scaffolds, and bioactive factors in strategic combinations to direct the in vitro formation of new tissues or organs (Fig. 1.1). Regenerative medicine strategies, on the other hand, often rely on the body's natural processes to assist in the formation of new tissues after delivery of exogenous cells, scaffolds, or biomolecules.
Figure 1.1 General schematic of tissue engineering strategy. (1) Cells are isolated from the patient and (2) expanded in 2D culture. (3) Expanded cells are then combined with various natural or engineered bioactive molecules (e.g., growth factors, nanoparticles, or DNA) into biocompatible scaffolds and (4) cultured under specific culture conditions to promote tissue formation. (5) Finally, functional tissue-engineered constructs are implanted into the donor to replace the damaged tissue.
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