Tissue Engineering Strategies for Organ Regeneration

Naznin Sultana, Sanchita Bandyopadhyay-Ghosh, Chin Fhong Soon, Naznin Sultana, Sanchita Bandyopadhyay-Ghosh, Chin Fhong Soon

• Publisher: CRC Press
• Year: 2020
• Print ISBN: 9781138391543
• eBook ISBN: 9780429749612
• Edition: 1
• Topic: Medicine
• Subtopic: Materials Science

Tissue Engineering Strategies for Organ Regeneration addresses the existing and future trends of tissue engineering approaches for organ/tissue regeneration or repair. This book provides a comprehensive summary of the recent improvement of biomaterials used in scaffold-based tissue engineering, and the tools and different protocols needed to design tissues and organs. The chapters in this book provide the in-depth principles for many of the supporting and enabling technologies including the applications of BioMEMS devices in tissue engineering, and the combination of organoid formation and three dimensional (3D) bioprinting. The book also highlights the advances and strategies for regeneration of three-dimensional microtissues in microcapsules, tissue reconstruction techniques, and injectable composite scaffolds for bone tissue repair and augmentation.

Key Features:

• Addresses the current obstacles to tissue engineering applications
• Provides the latest improvements in the field of integrated biomaterials and fabrication techniques for scaffold-based tissue engineering
• Shows the influence of microenvironment towards cell-biomaterials interactions
• Highlights significant and recent improvements of tissue engineering applications for the artificial organ and tissue generation
• Describes the applications of microelectronic devices in tissue engineering
• Describes different current bioprinting technologies

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, Mozafari Masoud^6,7 and Farshid Sefat^{2 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.

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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]

TABLE 1.1 The four main tissue types in the human body

Tissue Type	Location	Functions	Subtype
Epithelial	Cover inner and outer organ and body surfaces	Protection, secretion, absorption	Squamous, columnar, cuboidal, simple, pseudostratified, stratified
Connective	Between other tissues	Support and protect body	Loose and dense
Muscle	Attached to skeletal system, digestive system	Movement	Skeletal or striated, cardiac and smooth
Nervous	Distributed in the body	Regulates and controls physical functions	Central and peripheral system

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 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. Formation of connective tissue capsules (0.1-10 lm) around the implant, without any attachment to the implant surface	Zirconia, polymethyl metha acrylate (PMMA), alumina, titanium, etc
Bioactive materials	Interaction with tissue. Formation of new tissue around the implant and strongly merges with the implant surface	Bioglass, glass cerami...

Table of contents

• Cover
• Title Page
• Preface
• Copyright Page
• Table of Contents
• 1. Designing Biomaterials for Regenerative Medicine: State-ofthe-Art and Future Perspectives
• 2. New Generation Materials for Applications in Bone Tissue Engineering and Regenerative Medicine
• 3. Enhanced Scaffold Fabrication Techniques for Optimal Characterization
• 4. Next Generation Tissue Engineering Strategies by Combination of Organoid Formation and 3D Bioprinting
• 5. A Strategy for Regeneration of Three-Dimensional (3D) Microtissues in Microcapsules: Aerosol Atomization Technique
• 6. BioMEMS Devices for Tissue Engineering
• 7. Injectable Scaffolds for Bone Tissue Repair and Augmentation
• 8. Bio-Ceramics for Tissue Engineering
• 9. Stimulus-Receptive Conductive Polymers for Tissue Engineering
• 10. Evaluation of PCL/Chitosan/Nanohydroxyapatite/Tetracycline Composite Scaffolds for Bone Tissue Engineering
• Index
• Color Plate Section