Tissue Engineering

Clemens van Blitterswijk, Jan De Boer

• Publisher: Academic Press
• Year: 2014
• ISBN:
  9780124202108
• Edition: 2
• Topic: Biowissenschaften
• Subtopic: Biotechnologie

Tissue Engineering is a comprehensive introduction to the engineering and biological aspects of this critical subject. With contributions from internationally renowned authors, it provides a broad perspective on tissue engineering for students coming to the subject for the first time. In addition to the key topics covered in the previous edition, this update also includes new material on the regulatory authorities, commercial considerations as well as new chapters on microfabrication, materiomics and cell/biomaterial interface.

• Effectively reviews major foundational topics in tissue engineering in a clear and accessible fashion
• Includes state of the art experiments presented in break-out boxes, chapter objectives, chapter summaries, and multiple choice questions to aid learning
• New edition contains material on regulatory authorities and commercial considerations in tissue engineering

Chapter 1

Tissue Engineering

An Introduction

Lorenzo Moroni¹, Jan Schrooten², Roman Truckenmüller¹, Jeroen Rouwkema³, Jérôme Sohier⁴, and Clemens A. van Blitterswijk^{1 1}Department of Complex Tissue Regeneration, MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, Maastricht, The Netherlands ²Division of Skeletal Tissue Engineering, KU Leuven, Leuven, Belgium ³Laboratory of Biomechanical Engineering, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, The Netherlands ⁴Laboratory of Tissular Biology and Therapeutic Engineering _UMR 5305, Institute of Biology and Chemistry of Proteins, Centre National de la Recherche Scientifique, Lyon, France

Abstract

This chapter gives an illustrative introduction into the field of tissue engineering. The introduction is supported by the discussion of three classical experiments presented in a clearly arranged box format. The chapter also provides a well-commented and -motivated outline of the book's chapters. These chapters are substantially revised and updated compared to the first edition, covering subjects such as stem cells, extracellular matrix, biomaterials, scaffolds, drug-controlled release strategies, bioreactors, and actual “engineering” of different tissues and organ systems. Furthermore, the book is extended by a number of completely new chapters reporting on consolidated latest trends in the field. The latter includes topics such as “Materiomics,” here defined as the study of cell–material interactions employing high-throughput screening technology, or “organs on chips.” Finally, quality control, clinical translation, and ethical aspects are presented and discussed in view of the required steps to take care of when passing from the bench to the bed side.

Keywords

Biomaterials; High-throughput screening; Regenerative medicine; Scaffolds; Surface properties; Tissue engineering

In 1997, media all over the world were aroused by a BBC documentary, Tomorrow’s World, showing what is now known as the Vacanti mouse (Cao et al., 1997). The term “tissue engineering (TE)” was no longer seen as an expression familiar only to a limited number of scientists working in the field—it had become well-known to millions of individuals worldwide. Although the Vacanti experiment (Box 1.1) is truly exemplary for the discipline of tissue engineering, it is fair to say that the media upheaval was not so much caused by the actual experiment but even more by the spectacular sight of a nude mouse that had apparently grown a human ear on its back. This was not the first media hype on tissue or organ repair and most certainly will not be the last. It would not be difficult to dedicate an entire chapter in this textbook to the promising aspects of our discipline that made it to the media and had a major public impact. Whereas in the first edition of this book, it would have been difficult to fill an entire chapter with actual clinical successes, in this second edition we are witness to an increasing number of tissue engineering and regenerative medicine strategies successfully translated to patients. Yet, the eagerness of the media to report on the advances in the field of tissue engineering may give still the opposite impression. This is not so much caused by publicity of eager scientists; the actual cause is the enormous demand in our society for technologies that are able to repair, or even better regenerate, damaged or worn out tissues and/or organs.

On an annual basis, many millions of patients undergo surgery for tissue reconstruction. A fair proportion are treated satisfactorily, another portion less effectively, and millions still await treatments that would help them at least in an acceptable way. A now almost classical analysis on the need and commercial opportunity was published in Science in 1993 by Langer and Vacanti, the abstract of which is given below.

The loss or failure of an organ or tissue is one of the most frequent, devastating, and costly problems in human health care. A new field, tissue engineering, applies the principles of biology and engineering to the development of functional substitutes for damaged tissue. This article discusses the foundations and challenges of this interdisciplinary field and its attempts to provide solutions to tissue creation and repair.

Langer and Vacanti, 1993 (p. 920)

If the need is indeed so high, and the field has so extensively grown over the last decades, then why do we still have to improve upon the frequency of clinical successes? There are two major reasons for this phenomenon. First, bringing a relatively simple medical device from initial idea to a widespread clinical reality frequently takes a minimum of 10 years. As the underlying technology for developing tissue engineering products is less mature, and possibly more complex, it is to be expected that clinical progress in this field will be measured in decades rather than years. Second, tissue engineering is truly an interdisciplinary field where acquired knowledge from individual classical disciplines (e.g., quantum physics, polymer chemistry, molecular biology, anatomy) no longer suffices to make substantial leaps. Individuals active in this field will have to acquire multidisciplinary skills and be willing to look over the borders of their home discipline. The relatively young age of the field does not make it easy to acquire those skills as dedicated textbooks are still scarce and frequently do not address the appropriate audience by either offering a collection of research papers or by only dealing with a selected part of the entire discipline. Without the widespread availability of such textbooks, it is to be feared that the rapidly increasing number of graduate courses on tissue engineering may not be as effective as required, which may hamper the development of the field of tissue engineering into a mature scientific discipline.

With this in mind, in 2004 it was decided that it was time to bring together a representative group of internationally active scientists who would be willing to contribute to a textbook, which would address both the multidisciplinary nature of tissue engineering and the underlying base disciplines. From that time, the field has considerably matured. Tissue engineering witnessed not only more clinical successes, but also new discoveries in the basic sciences and new technologies and methods in the applied sciences converging into it. With respect to the first edition, the structure of the book has slightly changed. We still move from fundamental to translational research, but we have also introduced a scale level where topics will be framed from the small (e.g., small molecules) to the large scale (e.g., tissues and organs). This is framed in each chapter by a matrix identifying at which research and scale level the topic is located (Figure 1.1).

The rationale for this matrix originates from the intrinsic, interdisciplinary complexity of tissue engineering, the dynamics of the field, and also from the belief of the authors that this matrix can serve as a map for students to enter the world of tissue engineering.

Figure 1.1 Diagram sketching the layout of the book.

Tissue engineering is more than the sum of its ingredients. Their combinations create novel dimensions, insights, and questions that need to be addressed. Hence, a matrix-like chapter build-up represents better the interdisciplinary and translational road that tissue engineering has to travel, by showing logical links between all building blocks. The authors envision that this approach could turn this book into a handbook that can guide the next decade of research, bringing tissue engineering into the clinic and educating real tissue engineers.

The word “matrix” itself is already a good example of the new dimension that tissue engineering is creating. Matrix is an established term that is recognized both from the biology and from the engineering sides. For the former it represents a scale of tissue formation, an in vivo environment, and for the latter it is a tool that enables to develop a research strategy that builds on a multitude of variables and parameters. When these two definitions can be merged through the “matrix map” we have introduced, it would be a first sign that we have created a common language and that we are on the right track to engineer cell biology.

By using this “matrix map,” the reader will first be confronted with the fundamentals of the cell type that makes tissue engineering truly a part of regenerative medicine: the stem cell. Stem Cells (Chapter 2) gives insight into the different aspects of this cell and will show that the stem cell is not a single cell type but, in reality, encompasses different categories of cells ranging from the multipotent embryonic stem cell to the apparently less potent adult stem cell. With this knowledge, the reader will subsequently be guided to Tissue Formation during Embryogenesis (Chapter 3), where the formation of tissues in the embryo is discussed. Although most tissue engineers do not venture into the realms of developmental biology and research with a strong focus on developmental biology is just emerging in tissue engineering, we feel this should be strengthened in the future and hope that this chapter will urge more and more young scientists to enter into such an essential area, as it will allow them to better understand the mechanisms behind tissue and organ development, and implement them in new tissue engineering strategies. Obviously most tissue engineering constructs will not be implanted into embryos but into human beings after birth. Tissues in both the embryo and in an individual after birth usually, although not always, contain multiple cell types. Understanding how these cells interact is recognized as pivotal for the success of tissue engineering. Cellular Signaling (Chapter 4) provides such insights. Furthermore, in spite of all media attention that befalls stem cells, in reality cells represent only a small part of the dry weight of living tissue. All, or at least most, cells interact with an extracellular matrix (ECM), which, in contrast to the errant opinion of some engineers and even biologists, presents much more than mechanical support and adds substantially to the biological interactions in our body. As tissue engineering typically combines scaffolds with biologically active components such as cells or growth factors, we felt that a chapter on the biological equivalent the Extracellular Matrix as Bioscaffold in Tissue Engineering (Chapter 5) could not be missed. As many components of the ECM are considered as biomaterial sources, in this chapter we also introduce how the ECM itself can be used as a scaffold for tissue engineering.

At this point in the book a shift is made to the more fundamental engineering aspects. Most tiss...