Table Of Content“This comprehensive textbook begins with chapters covering the structural and functional biology of S
body tissues, their healing processes, and their regeneration and ends with a chapter looking toward the c
future commercialization of tissue-engineered scaffolds. It should be useful for those doing research on a
tissue-engineered scaffolds, companies developing tissue-engineered products, and clinicians looking to f
the future replacement of tissues in the clinic.” f
Prof. Allan S. Hoffman o
University of Washington, USA l
d
“The current volume provides an excellent basis to assist researchers in leaving the path of trial and error s
and designing scaffolds on the basis of true understanding. It is a must-read for anybody interested in f
tissue engineering.” o
Prof. Clemens A. van Blitterswijk r
University of Twente, the Netherlands T
i
“Tissue engineering is the most promising technology to treat various diseases by using cultured cells s
and will be a main actor in medical science in the 21st century. The fusion of medicine and engineering s
u
is essentially indispensable for tissue engineering, especially scaffold-based tissue engineering. This
very timely book will be equally useful for those who have engineering, medical, and biological science e
background.”
E
Prof. Teruo Okano
n
Tokyo Women’s Medical University, Japan
g
Scaffolds for tissue engineering are devices that exploit specific and complex physical and biological i
functions, in vitro or in vivo, and communicate through biochemical and physical signals with cells n
and, when implanted, with the body environment. Scaffolds are produced mainly with synthetic e
materials, and their fabrication technologies are derived from already well-established industrial e
processes, with some new specific technologies having been developed in the last years to address r
required complexities. i
n
Often, a generalist approach is followed for the translation of materials and technologies designed g
for other applications, without considering the specific role of scaffolds from a physical and biological
point of view. The book illustrates scaffold design principles, with particular relevance to the
biological requirements needed to control and drive the biological cross talk, and reviews materials
and fabrication and validation methods.
Claudio Migliaresi is professor of composite materials engineering and of
biomaterials and biomedical technologies, head of the Department of Industrial M
Engineering, dean of the School of Industrial Engineering, and head of the BIOtech
i
Research Center of the University of Trento, Italy. His research activities range g
l
from composite materials to biodegradable polymers, biomaterials, materials, and i
a
scaffolds for tissue engineering. Prof. Migliaresi has published about 200 papers,
r
edited the five volumes of the book Polymers in Medicine, and owns some patents. e
edited by
s
i
Antonella Motta is assistant professor at the University of Trento and has qualified Claudio Migliaresi
as associate professor of bioengineering by the Italian evaluation system. She |
teaches bioengineering and tissue engineering and regenerative medicine courses. M Antonella Motta
Prof. Motta’s research activities are mainly focused on nature-derived polymers
o
for tissue engineering applications, scaffold design, and interactions of material–
t
biological systems. She has published about 90 papers, edited several chapters on t
a
tissue engineering, and owns some patents.
V391
ISBN 978-981-4463-20-1
Scaffolds for
Tissue Engineering
(cid:49)(cid:66)(cid:79)(cid:1)(cid:52)(cid:85)(cid:66)(cid:79)(cid:71)(cid:80)(cid:83)(cid:69)(cid:1)(cid:52)(cid:70)(cid:83)(cid:74)(cid:70)(cid:84)(cid:1)(cid:80)(cid:79)(cid:1)(cid:51)(cid:70)(cid:79)(cid:70)(cid:88)(cid:66)(cid:67)(cid:77)(cid:70)(cid:1)(cid:38)(cid:79)(cid:70)(cid:83)(cid:72)(cid:90)(cid:1)(cid:137)(cid:1)(cid:55)(cid:80)(cid:77)(cid:86)(cid:78)(cid:70)(cid:1)(cid:19)
Scaffolds for
Tissue Engineering
Biological Design, Materials, and Fabrication
editors
Preben Maegaard edited by
Anna Krenz
Claudio Migliaresi
Wolfgang Palz
Antonella Motta
The Rise of Modern Wind Energy
Wind Power
for the World
Published by
Pan Stanford Publishing Pte. Ltd.
Penthouse Level, Suntec Tower 3
8 Temasek Boulevard
Singapore 038988
Email: [email protected]
Web: www.panstanford.com
British Library Cataloguing-in-Publication Data
A catalogue record for this book is available from the British Library.
Scaffolds for Tissue Engineering: Biological Design, Materials,
and Fabrication
All rights reserved. This book, or parts thereof, may not be reproduced in any form
Copyright © 2014 by Pan Stanford Publishing Pte. Ltd.
or by any means, electronic or mechanical, including photocopying, recording
or any information storage and retrieval system now known or to be invented,
without written permission from the publisher.
For photocopying of material in this volume, please pay a copying fee through
the Copyright Clearance Center, Inc., 222 Rosewood Drive, Danvers, MA 01923,
USA. In this case permission to photocopy is not required from the publisher.
ISBN 978-981-4463-20-1 (Hardcover)
ISBN 978-981-4463-21-8 (eBook)
Printed in the USA
Contents
Preface
1. Ov ervie w: An Evolving State of the Art in Tissue xvii
Engineering 1
Anthony T. DiBenedetto
2. The Functional Role of Extracellular Matrix 21
Eleonora Carletti, Matteo Stoppato, Claudio Migliaresi,
and Antonella Motta
2.1 Introduction 22
2.2 ECM Functions 24
2.2.1 Biochemical Properties 24
2.2.2 Physical Properties 25
2.2.3 Mechanical Transduction 27
2.3 ECM Main Components 29
2.3.1 Collagens: The Major Fibrous
Component 29
2.3.1.1 Chemical composition:
collagen types 30
2.3.2 Elastin: The Elastic Component 31
2.3.3 Fibronectin: A Binding Protein 33
2.4 ECM Assembling and Organization 34
2.4.1 ECM Organization Function Dependent:
Some Examples 35
2.4.1.1 Aorta wall 35
2.4.1.2 Bone 37
2.4.1.3 Hyaline Cartilage 38
2.4.1.4 Fibrocartilage (the meniscus
case) 39
2.4.1.5 Skeletal muscle 40
2.5 ECM Development and Remodeling 41
2.5.1 ECM in the Healing Process 42
2.5.1.1 Inflammation 42
2.5.2 A Lesson from Fetal Healing: Scarless
Regeneration 43
vi Contents
3. The Premise of Tissue Engineering: Molecular Recognition 57
Christopher J. Pateman and John W. Haycock
3.1 Introduction 58
3.2 Biomaterials: From Medical Devices to Tissue
Scaffolds 59
3.2.1 Natural ECM materials 61
3.3 Physical Properties of Scaffolds that Influence
Molecular Bio-Recognition 61
3.3.1 Modification at the Interface 64
3.3.2 Stem Cell Differentiation: Physical and
Topographic Properties 65
3.3.3 Multi-functional Biological Matrices for
Directing Cellular Response 68
4. 3Pr.4in cipleCso anncdlu Bsiioonlosg aicnadl PFautthuwrea yDsi rtoec Ttiisosnuse 69
Regeneration: The Tissue Regenerative Niche 79
Ranieri Cancedda and Claudia Lo Sicco
4.1 Introduction 80
4.2 Platelet-Derived Growth Factors 84
4.3 Inflammation 86
4.4 Hypoxia 89
4.5 Angiogenesis and Vasculogenesis 90
4.6 Locally Resident Pluripotent Cells and
Circulating Stem/Progenitors Cells 92
4.7 Fracture Healing Cascade: A Paradigm of
k
Tissue Repair/Regeneration 94
4.7.1 NF- B: A Main Biological Pathway
5. Host Response tAoc Btiivoamteadte driuarlisn g Tissue Regeneration 19185
Sangeetha Srinivasan and Julia E. Babensee
5.1 Introduction 116
5.2 A Typical FBR 117
5.2.1 Cellular and Molecular Aspects 117
5.2.2 Deleterious Outcomes 120
5.2.2.1 Fibrosis, FBGC, and material
degradation 120
5.2.3 Biomaterial Strategies to Affect Aspects
of the Foreign Body Response 121
Contents vii
5.3 Instant Blood-Mediated Inflammatory
Reaction 122
5.3.1 Biomaterial Intervention for IBMIR 124
5.4 Immune Response in the Context of
Biomaterials 127
5.4.1 Types of Immune Responses 127
5.4.1.1 Innate immunity 127
5.4.1.2 Adaptive immunity 133
5.4.2 Biomaterial Strategies to Affect
Adaptive Immune Responses 137
5.4.2.1 DC-mediated biomaterial
adjuvant effect 139
5.4.2.2 Biomaterials-based
adjuvants and vaccines 141
5.4.2.3 Biomaterial-based
engineering anti-tumor
immunity 143
5.4.2.4 Biomaterials and tolerance
toward tissue-engineered
devices (TEDs)/transplants 145
5.5 Constructive Remodeling and Effective Host
Integration of Implants 146
5.5.1 Cell Injury and Repair 146
5.5.2 Stages of Wound Healing 147
5.5.2.1 Activation of platelets and
blood coagulation 147
5.5.2.2 Inflammation 148
5.5.2.3 Re-epithelialization,
granulation tissue, and
angiogenesis 149
5.5.2.4 Matrix, scar formation, and
remodeling 149
5.5.3 Biomaterial Strategies Employed to
Direct Repair and Regeneration 151
5.5.3.1 Wound closure and
vascularization 151
5.5.3.2 Stem cell-seeded SCs to
direct regeneration 154
5.5.3.3 Remodeling of the ECM 155
viii Contents
5.5.3.4 Biodegradable and
bioresorbable polymers 156
6. 5Sc.6a ffoldS Vuamscmualarryiz ation 115763
Lindsay E. Fitzpatrick, Alexandra Lisovsky,
Ema C. Ciucurel, and Michael V. Sefton
6.1 Introduction 174
6.2 The Native Vascular Network 174
6.2.1 Angiogenesis: The Formation of
New Blood Vessels 176
6.3 Vascularization of Biomaterial Scaffolds 178
6.3.1 GF Delivery 179
6.3.1.1 Single GF delivery 179
6.3.1.2 Multiple GF delivery 183
6.3.2 Cell Delivery and Transplantation 184
6.3.2.1 Scaffolds seeded with cells 184
6.3.2.2 Modular tissue engineering 186
6.3.2.3 Genetically modified
GF-producing cells 189
In6 s.3it.u2.4 Scaffold-free cell delivery
approaches 190
6.3.3 Vascularization with
Endogenous Cells 192
6.3.4 Scaffold Prevascularization 195
6.3.5 Decellularized Scaffolds 197
6.3.6 Angiogenic Biomaterials 199
6.3.7 Microfabrication Methods 202
6.4 Limitations and the Road Ahead 203
6Th.5e RoleS uomf Omsateroy blasts in in vitro Vascularization 220149
7. Engineering Biomimetic Scaffolds 223
Nasim Annabi, Nihal Engin Vrana, Pinar Zorlutuna,
Fariba Dehghani, and Ali Khademhosseini
7.1 Approaches to Engineer Biomimetic
Constructs 224
7.1.1 Fabrication of 3D Biomimetic
Scaffolds 225
7.1.1.1 Rapid prototyping (RP) 225
