Table Of ContentTissue Engineering Strategies for
Organ Regeneration
Editors
Naznin Sultana
Medical Academy, Prairie View A&M University, Texas, USA
Sanchita Bandyopadhyay-Ghosh
Department of Mechanical Engineering
Manipal University Jaipur
Rajasthan, India
Chin Fhong Soon
Biosensor and Bioengineering Laboratory
Microelectronics and Nanotechnology-Shamsuddin
Research Centre (MiNT-SRC)
AND
Faculty of Electrical and Electronic Engineering
Universiti Tun Hussein Onn Malaysia
Batu Pahat, Johor, Malaysia
p,
A SCIENCE PUBLISHERS BOOK
Cover credit: Cover illustrations reproduced by kind courtesy of Dr. Mohd. Izzat Hassan and Mr. Kapender Phogat.
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Library of Congress Cataloging‑in‑Publication Data
Names: Sultana, Naznin, editor. | Bandyopadhyay-Ghosh, Sanchita, 1971-
editor. | Soon, Chin Fhong, 1974- editor.
Title: Tissue engineering strategies for organ regeneration / editors,
Naznin Sultana, Sanchita Bandyopadhyay-Ghosh, Chin Fhong Soon.
Description: Boca Raton : CRC Press, Taylor & Francis Group, [2020] |
Includes bibliographical references and index.
Identifiers: LCCN 2019036051 | ISBN 9781138391543 (hardback)
Subjects: LCSH: Tissue scaffolds. | Guided tissue regeneration. | Tissue
engineering. | Biomedical materials. | Regeneration (Biology)
Classification: LCC R857.T55 T574 2020 | DDC 610.28--dc23
LC record available at https://lccn.loc.gov/2019036051
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Preface
Tissue Engineering Strategies for Organ Regeneration addresses the multidisciplinary tissue
engineering approaches in regenerating different types of tissues and organs. This book provides a
comprehensive summary of the recent improvements of biomaterials used in scaffold-based tissue
engineering and describes the different protocols for the manufacture of scaffolds. In addition,
it describes the mechanisms behind cell-biomaterials interactions. In addition, this book focuses
on advanced technologies such as microfabrication techniques for tissue engineering approaches.
Several in vitro and in vivo functions of tissue engineering scaffolds for several applications are
provided. Tissue engineering scaffolds with multifunctional properties such as biocompatibility,
conductivity and antibacterial characteristics are addressed in the book. This book not only
addresses the present constraints in tissue engineering applications but also highlights the future
directions of tissue engineering applications.
This book is written by experts from around the world in tissue engineering field. Chapter 1
focuses on designing biomaterials for regenerative medicine: state-of-the-art and future perspectives.
Chapter 2 deals with new generation materials for applications in bone tissue engineering and
regenerative medicine. Chapter 3 discusses enhanced scaffold fabrication techniques for optimal
characterization. Chapter 4 describes next generation tissue engineering strategies by combination
of organoid formation and 3D bioprinting. Chapter 5 provides a strategy for regeneration of three-
dimensional (3D) microtissues in microcapsules: aerosol atomization technique. Chapter 6 highlights
BioMEMS devices for tissue engineering. Chapter 7 focuses on injectable scaffolds for bone tissue
repair and augmentation. Chapter 8 presents the details associated with bio-ceramics for tissue
engineering. Chapter 9 reviews stimulus-receptive conductive polymers for tissue engineering.
Chapter 10 delivers PCL /Chitosan/Nanohydroxyapatite/Tetracycline composite scaffolds for bone
tissue engineering.
All the chapters of this book are self-contained and focused on current tissue engineering
strategies for organ restoration. It is expected that the book will be a great resource and reference for
the multidisciplinary societies such as the Researchers, Advanced Undergraduate and Postgraduate
students in Biomedical Engineering, Materials Engineering, Chemical Engineering, and Clinical
investigators.
Naznin Sultana
Sanchita Bandyopadhyay-Ghosh
Chin Fhong Soon
Contents
Preface iii
1. Designing Biomaterials for Regenerative Medicine:
State-of-the-Art and Future Perspectives 1
Zohreh Arabpour, Mansour Youseffi, Chin Fhong Soon, Naznin Sultana,
Mohammad Reza Bazgeir, Masoud Mozafari and Farshid Sefat
2. New Generation Materials for Applications in Bone Tissue
Engineering and Regenerative Medicine 10
Ravikumar K, Ashutosh Kumar Dubey and Bikramjit Basu
3. Enhanced Scaffold Fabrication Techniques for Optimal Characterization 23
Tshai Kim Yeow, Lim Siew Shee, Yong Leng Chuan and Chou Pui May
4. Next Generation Tissue Engineering Strategies by Combination of
Organoid Formation and 3D Bioprinting 51
Shikha Chawla, Juhi Chakraborty and Sourabh Ghosh
5. A Strategy for Regeneration of Three-Dimensional (3D) Microtissues in
Microcapsules: Aerosol Atomization Technique 63
Chin Fhong Soon, Wai Yean Leong, Kian Sek Tee, Mohd Khairul Ahmad
and Nafarizal Nayan
6. BioMEMS Devices for Tissue Engineering 81
Tao Sun and Chao Liu
7. Injectable Scaffolds for Bone Tissue Repair and Augmentation 91
Subrata Bandhu Ghosh, Kapender Phogat and Sanchita Bandyopadhyay-Ghosh
8. Bio-Ceramics for Tissue Engineering 126
Hasan Zuhudi Abdullah, Te Chuan Lee,
Maizlinda Izwana Idris and Mohamad Ali Selimin
9. Stimulus-Receptive Conductive Polymers for Tissue Engineering 144
Naznin Sultana
10. Evaluation of PCL / Chitosan/Nanohydroxyapatite / Tetracycline
Composite Scaffolds for Bone Tissue Engineering 157
Rashid Bin Mad Jin, Naznin Sultana, Chin Fhong Soon and Ahmad Fauzi Ismail
Index 171
Color Plate Section 173
1
Designing Biomaterials for
Regenerative Medicine: State-of-
the-Art and Future Perspectives
Zohreh Arabpour1, Mansour Youseffi2, Chin Fhong Soon3, Naznin Sultana4,
Mohammad Reza Bazgeir5, Masoud Mozafari6, 7 and Farshid Sefat2, 8*
1.1 INTRODUCTION
The complexity of the human body can be simplified when stating the matter from which it is
composed. To expand, the body is known to be made up of four tissue types, including epithelial
tissue, neural tissue, muscle tissue and connective tissue. Each tissue type is created from a
varying physiology, which contributes to the functionality of the matter. For example, the muscle
tissue is rich in mitochondria due to the excessive need for oxygen in order for it to function
with great exertion of energy. Table 1.1 demonstrates the four tissue types, and clarifies both the
functionality of the matter alongside the cells within the tissue which allows the tissue type to
work as it should.
1 Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran
University of Medical Sciences, Tehran, Iran.
2 Department of Biomedical and Electronics Engineering, School of Engineering, University of Bradford, Bradford, UK.
3 Biosensor and Bioengineering Lab, MiNT-SRC, Faculty of Electrical and Electronic Engineering, Universiti Tun Hussein
Onn Malaysia, 86400 Parit Raja, Batu Pahat, Johor, Malaysia.
4 Medical Academy, Prairie View A&M University, TX 77446, USA.
5 Royal National Orthopaedic Hospital, Brockley Hill, London, UK.
6 Bioengineering Research Group, Nanotechnology and Advanced Materials Department, Materials and Energy Research
Center (MERC), Tehran, Iran.
7 Department of Tissue Engineering & Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran
University of Medical Sciences, Tehran, Iran.
8 Interdisciplinary Research Centre in Polymer Science & Technology (IRC Polymer), University of Bradford, Bradford,
UK.
* Corresponding author: [email protected]
1
2 Tissue Engineering Strategies for Organ Regeneration
TABLE 1.1 The four main tissue types in the human body
Tissue Type Location Functions Subtype
Epithelial Cover inner and outer organ and Protection, secretion, absorption Squamous, columnar, cuboidal,
body surfaces simple, pseudostratified,
stratified
Connective Between other tissues Support and protect body Loose and dense
Muscle Attached to skeletal system, Movement Skeletal or striated, cardiac
digestive system and smooth
Nervous Distributed in the body Regulates and controls physical Central and peripheral system
functions
1.2 ORGAN SYSTEMS
There are 11 main organ systems in the human body, composed of different variations of the main
tissue types. These organ systems are vital to quality of life, and if one organ within a system fails
to carry out its purpose, fatality could occur, hence the need of tissue engineering intervention.
Trauma is one of the main causes for organ failure, and the body responds through expressing genes,
growth factors and activating cells as a healing process. Unfortunately, humans do not possess the
capability to regrow limbs, such as the salamander; however in terms of natural tissue growth, the
extracellular matrix for some tissues (such as simple connective) can be rebuilt to a certain extent
(Krafts 2010, Zadpoor 2015).
As technology has advanced, novel methods have been developed and tested, portraying that
synthetic tissues can exponentially increase the duration of a life cycle, by allowing continuity of
functioning organ systems. Examples of beneficial tissue regeneration include creation of blood
vessels for cardiac patients, bone scaffolds for amputees, skin grafts for burn patients and many
more, to be discussed further in the chapter.
1.3 ESSENTIAL REQUIREMENTS IN DESIGNING BIOMATERIALS FOR TISSUE
ENGINEERING AND REGENERATIVE MEDICINE APPLICATIONS
1.3.1 Mechanical Requirements
The chemical and physical optimization of new biomaterials in order to interact with living cells are
being studied by many research groups (Khan and Tanaka 2017). Synthetic or hybrid biomaterials
should be developed to adapt for living systems or live cells in vitro and in vivo. The selection and
design of an appropriate biomaterial is determined by specific application of scaffold. Some of
the mechanical properties that are of utmost importance are hardness, plasticity, elasticity, tensile
strength and compressibility. For example, ceramics such as hydroxyl apatite (HAp), and tricalcium
phosphate (TCP) are appropriate for bone regeneration (Khan and Tanaka 2017). The scaffold of
the bioceramic should mimic mechanical properties of the anatomical location that will be planted
and the degradation rate should be consistent with bioactive surface for suitable tissue regeneration.
Since the regeneration rates of bone are different for different age groups, this must be taken into
consideration when designing scaffolds because the rate of regeneration in older adults is slower
than young individuals (O’Brien 2011).
Maintaining the mechanical behavior of implanted scaffolds structure and tolerance of stress and
loads during the reconstruction is very important. The stability of scaffolds in biological systems
depends on some factors such as stress, strength, elasticity, temperature and absorption of the material
associated with chemical degradation. Therefore, in order to select an appropriate biomaterial,
it is important to assess some of the following properties: (1) Elastic behavior—measurement of
Designing Biomaterials for Regenerative Medicine: State-of-the-Art and Future Perspectives 3
pressure in response to tensile or compressed stress during the force. This reversible behavior could
be assessed by linear relation between stress and strain. Stress is a measure of load and strain is a
measure of displacement; (2) Plastic behavior—when (or compression) uniaxial tensile stress reaches
yield strength, permanent deformation occurs; (3) Tensile strength—the highest stress that material
can endure before breakdown; (4) Ductility—the plastic strain at failure. Plasticity before breaking;
(5) Toughness—the energy needed to break a unit volume of material; (6) Flexural behavior—
the relationship between a flexural stress and strain in response to a tensile or compressive stress
perpendicular to the bar. The mechanical behavior of materials can be equated by some factors.
Swelling, porosity pore size, shape, orientation, and connectivity are some of these factors that
directly impacts mechanical properties of the biomaterial (Olson et al. 2011).
The balance between mechanical behaviors and porous pattern allowing cell penetration and
vascularization is necessary to ensure success of scaffolds in tissue engineering. The mechanical
stiffness as well as the roughness of materials and the physical stimulation of the three-dimensional
microstructure of the scaffold significantly influence the cellular regeneration, cellular polarization
and balanced intracellular signaling (Olson et al. 2011).
1.3.2 Biological Requirements
Production of appropriate scaffolds to support the proliferation and differentiation of cells to mimic
biological function of extracellular matrix proteins is another essential step to generate appropriate
3D biomimetic scaffolds in tissue engineering (Chiono et al. 2009). Biocompatibility of scaffolds
must be ensured, to avoid undesirable immune responses to the implant and ectopic calcifications in
vivo. The surface of biomaterials should have excellent chemical properties to improve attachment,
migration, proliferation, and differentiation of cells (Mandal et al. 2009).
Biomaterials used as scaffold in tissue engineering should be non-toxic to eliminate inflammatory
or allergic reactions in the human body (Moztarzadeh et al. 2018). The human body’s response
to the implant determines the success of the implanted biomaterial, and assesses the degree of
biocompatibility of a substance. The tissue response to the materials and materials’ degradation in
the body system are two major factors that affect the biocompatibility of biomaterial (Sefat et al.
2018). In this context, biodegradability should be controllable to support the formation of new tissue
(Grayson et al. 2003). After a biomaterial implant is exposed to the body, tissues start to react to the
implant surface. The body responses to implants are: (1) Thrombosis or coagulation of blood after
platelets are attached to the surface of implant and, (2) Formation of fibrous capsule around the
surface of implant (Chiono et al. 2009). The kind of reactions depends on type of biomaterial that
is used in the implants. Biomaterials based on the body responses can be classified into three main
groups: bioinert, bioactive and bioresorbable. The bioresponses and examples of each classified
biomaterials are as shown in Table 1.2 (Geetha et al. 2009).
TABLE 1.2 Biomaterials classification and interaction with tissue
Classification Response Examples
Bioinert materials Minimal interaction with tissue. Zirconia, polymethyl metha acrylate
Formation of connective tissue capsules (PMMA), alumina, titanium, etc
(0.1-10 lm) around the implant, without any
attachment to the implant surface
Bioactive materials Interaction with tissue. Bioglass, glass ceramic, synthetic,
Formation of new tissue around the implant and hydroxyl apatite (HAP)
strongly merges with the implant surface
Bioresorbable materials Dissolved and replaced by the advanced tissue Polyglycolic acid and Polylactic, tricalcium
phosphate, composites of proteins
