Tissue Engineering for Artificial Organs

Regenerative Medicine, Smart Diagnostics and Personalized Medicine

Anwarul Hasan

• Publisher: Wiley-VCH
• Year: 2017
• Print ISBN:
  9783527338634
• Edition: 1
• eBook ISBN:
  9783527689965
• Topic: Biological Sciences
• Subtopic: Biotechnology
• Index: Biological Sciences

A comprehensive overview of the latest achievements, trends, and the current state of the art of this important and rapidly expanding field.
Clearly and logically structured, the first part of the book explores the fundamentals of tissue engineering, providing a separate chapter on each of the basic topics, including biomaterials stem cells, biosensors and bioreactors. The second part then follows a more applied approach, discussing various applications of tissue engineering, such as the replacement or repairing of skins, cartilages, livers and blood vessels, to trachea, lungs and cardiac tissues, to musculoskeletal tissue engineering used for bones and ligaments as well as pancreas, kidney and neural tissue engineering for the brain. The book concludes with a look at future technological advances.
An invaluable reading for entrants to the field in biomedical engineering as well as expert researchers and developers in industry.

Part I
Fundamentals

Chapter 1
Introduction to Tissue Engineering

Rami Mhanna and Anwarul Hasan

1.1 Introduction

Tissue engineering is an interdisciplinary field that utilizes cells, biomaterials, biochemical (e.g., growth factors) and physical (e.g., mechanical loading) signals, as well as their combinations to generate tissue-like structures [1]. The goal of tissue engineering is to provide biological substitutes that can maintain, restore, or improve the function of damaged tissues [2]. Although the first tissue-engineered skin products were introduced in the late 1970s and early 1980s giving rise to modern tissue engineering, the term “tissue engineering” was coined only in 1987 [3–6].

In fact, the use of prosthesis (e.g., gold for tooth replacement and wood for limbs and toes) was employed as early as ancient Egyptians. However, these treatments were all based on nonliving materials, which provided some structure and function but were very far from the original tissue. Medical development led, in the middle of the twentieth century, to the possibility of replacing an entire organ with an organ from a donor, known today as organ transplantation [7]. Although this is widely practiced today and is known to be the ultimate solution for organ failure, the need for organs always surpasses the number of available donated organs [8]. The limited donor availability and rejection of the grafts by the immune system drove the concept of in vitro grown tissues. The success in tissue engineering of skin grafts boosted the interest in applying similar concepts to other tissues and organs [9]. However, the relatively simple structure, the limited vascular demands of skin, and the ease of growing keratinocytes in vitro are not common to most tissues. The dream of regenerating tissues in vitro faced major hurdles associated with the engineering of complex, three-dimensional (3D), vascularized multicellular tissues.

In this chapter, we provide a brief introduction to tissue engineering. The clinical needs for tissue engineering, the history, the fundamentals, and the applications of tissue engineering are discussed in brief. The recent advancements in the field, as well as some of the major challenges and the future of tissue engineering, are also briefly discussed.

1.2 Clinical Need for Tissue Engineering and Regenerative Medicine

The clinical need for tissue engineering and regenerative medicine is the result of our urge to treat defective tissues. Regardless of how such defects occurred (congenital or acquired), traditional medical tools are not yet capable of completely or efficiently fixing them. In fact, traditional medicine has severe limitations in delivering solutions for numerous health problems. Injuries and diseases are traditionally treated using pharmaceuticals, whereas prosthetic devices and organ transplantation are used in more severe conditions. While pharmaceuticals may be useful for the treatment of numerous conditions, they cannot cure a number of deadly diseases (e.g., several forms of cancers, strokes, diabetes, etc.) or diseases at their advanced stages (e.g., Alzheimer's, Parkinson's, osteoarthritis, etc.). On the other hand, prosthetic devices are not capable of restoring normal function, and the number of organ donors is always way less than required. Tissue engineering can be used to treat diseases that cannot be cured with regular pharmaceuticals and to provide natural, living, functional organs to overcome the need for donors and prosthetics.

The main goal of tissue engineering is the development of functional substitutes for damaged tissues [2]. It is estimated that the majority of tissue engineering products are used for the treatment of injuries and congenital defects, while tissue engineering products used for the treatment of diseases are less common. The worldwide tissue engineering and cell therapy market has been estimated in 2014 at about $15 billion and is expected to grow up to $32 billion by 2018. The dominant market is in the orthopedic, musculoskeletal, and spine areas followed by the skin, nervous tissues, and other organs [10]. Skin was the first tissue to be engineered; this is because of the relatively simple structure of the tissue (can be prepared using two-dimensional (2D) culture and has easy access to culturing medium). Skin is also an important tissue engineering target because of the high demand especially resulting from war burns. Skin damage can cause disfigurement and disability, which may lead to further serious infections and psychological damage to patients. All these factors made skin one of the first clinical tissue engineering targets. Tissue engineering and regenerative medicine solutions can also be applied for any tissue, although the levels of complexity would differ between targets. Examples include the heart, kidneys, cornea, nervous tissues, liver, intestines, pancreas, lungs, bone, muscle, and so on. The ultimate goal is that tissue engineering and regenerative medicine would one day be able to overcome the need for organ transplantation. The medical need for tissue engineering and regenerative medicine can be emphasized in the donor waiting list, which is always increasing at a higher pace than the number of organ donors. The ability to engineer such organs or help them regenerate would represent a great leap in the history of the health care field.

1.3 History of Tissue Engineering and Regenerative Medicine

Generating new tissues and restoring body parts or organs are ideas that were embedded in humans' imaginary world from the dawn of history. The revolution of the human race enabled these imaginary notions to become well-practiced findings all over the years. In the case of the ancient Egyptians, restoring body parts was reasoned by the importance of reuniting and reassembling the body to enable revitalization in the Afterlife, as inscribed in spells known as the “Pyramid Texts” (2375 BC) [11]. It is believed that the first dental prosthesis was constructed from gold in Egypt around 2500 BC [12]. Nerlich and colleagues account for an ancient Egyptian false big toe believed to be the oldest limb prosthesis (950–710 BC), Figure 1.1a [13]. Interestingly, this prosthesis was recently found to improve function and walking, which indicates the possibility that the purpose of these designs was not only for the Afterlife [14].

Figure 1.1 Some random images showing the development of regenerative medicine throughout different eras in history. (Nerlich 2000 [13]. Reproduced with permission of Elsevier.) (a) 2500 BC: false big toe developed in ancient Egypt. (b) 278 AD: Saints Cosmas and Damian performing a leg transplant from a deceased donor onto a patient with an amputated leg. (Zimbler 2001 [15]. Wikipedia, public domain, https://commons.wikimedia.org/wiki/File: Fra_Angelico_064.webp.) (c) In 2013, Chinese doctors saved a man's severed hand by grafting it to his ankle before later reattaching it to the patient's arm.

(Gordon 2006 [21]. Reproduced with permission of John Wiley and Sons.)

The use of nonliving materials enabled the restoration of the structure, shape, and function to some extent. However, living tissues would be needed to achieve a full recovery. History notes the mirac...

Table of contents

• Cover
• Title Page
• Title Page
• Copyright
• Table of Contents
• List of Contributors
• Foreword
• Preface
• Volume 1
• Volume 2
• Index
• End User License Agreement