Handbook of Tissue Engineering Scaffolds: Volume Two

Masoud Mozafari, Farshid Sefat, Anthony Atala

• Publisher: Woodhead Publishing
• Year: 2019
• Print ISBN: 9780081025611
• eBook ISBN: 9780081025628
• Topic: Technology & Engineering
• Subtopic: Biotechnology in Medicine
• Index: Technology & Engineering

Handbook of Tissue Engineering Scaffolds: Volume Two provides a comprehensive and authoritative review on recent advancements in the application and use of composite scaffolds in tissue engineering. Chapters focus on specific tissue/organ (mostly on the structure and anatomy), the materials used for treatment, natural composite scaffolds, synthetic composite scaffolds, fabrication techniques, innovative materials and approaches for scaffolds preparation, host response to the scaffolds, challenges and future perspectives, and more. Bringing all the information together in one major reference, the authors systematically review and summarize recent research findings, thus providing an in-depth understanding of scaffold use in different body systems.- Dedicated to the specialist topic of composite scaffolds, featuring all human body systems- Covers basic fundamentals and advanced clinical applications- Includes up-to-date information on preparation methodology and characterization techniques- Highlights clinical data and case studies

Part Six

Neural tissue engineering scaffolds

Outline

1. 34. Scaffolds for brain tissue reconstruction
2. 35. Scaffolds for spinal cord regeneration
3. 36. Scaffolds for bridging sciatic nerve gaps
4. 37. Scaffold for facial nerve reconstruction
5. 38. Scaffolds for auditory nerve regeneration

34

Scaffolds for brain tissue reconstruction

Dayo O. Adewole ^{1 , 2 , 3} , Suradip Das ^{1 , 3} , Dmitriy Petrov ^{1 , 3} , and D. Kacy Cullen ^{1 , 2 , 3 1} Center for Brain Injury & Repair, Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States ² Department of Bioengineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA, United States ³ Center for Neurotrauma, Neurodegeneration & Restoration, Corporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, PA, United States

Abstract

The brain is the most complex organ in the human body, functionally comprised of over 100 billion nerve cells, called neurons, that are precisely interconnected by a sophisticated network of over 100,000 miles of fibrous extensions, called axons. This is a challenging issue to properly regenerate brain tissue. The focus of this chapter is on brain repair, specifically emerging strategies to facilitate regeneration, reconnectivity, and/or reconstruction of these exquisite neuronal–axonal–glial networks following degeneration caused by brain injury or neurodegenerative disease. Focus is given to engineered scaffold-based approaches; in particular, efforts encompassing naturally occurring organic/biologically derived scaffolds (e.g., extracellular matrices [ECMs]), non-ECM polymer-based scaffolds (e.g., hydrogels), and so-called “living scaffolds” (e.g., anisotropic cell-laden scaffolds). In general, these biomaterial/biological scaffolds aim to fill defects, provide structural support, provide guidance cues (generally anisotropic), deliver biological agents, and/or provide preorganized cells. The design criteria for these scaffolds are generally determined by the desired mechanism(s) of action, which for brain repair generally fall into three categories: (1) neuroprotection by providing prosurvival cues (growth factors) and/or supporting cells; (2) cell replacement by eliciting neurogenesis, glial proliferation, orchestrating (endogenous) cell migration, and/or providing new (exogenous) cells, with varying degrees of three-dimensional (3D) architecture; and (3) neurite pathfinding (generally axonal) to restore local connections and/or reconstruct long-distance circuitry. The ultimate goal of these therapies is to prevent cell/axonal loss, promote healing, reconstruct lost neural architecture/connections, and ultimately facilitate functional recovery following nervous system disorders.

Keywords

Astrocytes; Axon regeneration; Biomaterials; Brain; Extracellular matrix; Growth factors; Living scaffolds; Nervous system; Neurons; Scaffolds; Tissue engineering

34.1. Overview of brain reconstruction: scaffold types and design objectives

The brain is the most complex organ in the human body, functionally comprised of over 100 billion nerve cells, called neurons, that are precisely interconnected by a sophisticated network of over 100,000 miles of fibrous extensions, called axons [1,2]. These exquisite neuronal–axonal networks are complimented by an array of specialized support cells, collectively called glia, that are 10 times more numerous than neurons yet fulfill necessary roles including providing structural, trophic, metabolic, and functional support for neurons and axonal tracts [1]. The focus of this chapter is on brain repair, specifically emerging strategies to facilitate regeneration, reconnectivity, and/or reconstruction of these exquisite neuronal–axonal–glial networks following degeneration caused by brain injury or neurodegenerative disease. Focus is given to engineered scaffold-based approaches; in particular, efforts encompassing naturally occurring organic/biologically derived scaffolds (e.g., extracellular matrices (ECMs)), non-ECM polymer-based scaffolds (e.g., hydrogels), and so-called “living scaffolds” (e.g., anisotropic cell-laden scaffolds). In general, these biomaterial/biological scaffolds aim to fill defects, provide structural support, provide guidance cues (generally anisotropic), deliver biological agents, and/or provide preorganized cells. The design criteria for these scaffolds are generally determined by the desired mechanism(s) of action, which for brain repair generally fall into three categories: (1) neuroprotection by providing prosurvival cues (growth factors) and/or supporting cells; (2) cell replacement by eliciting neurogenesis, glial proliferation, orchestrating (endogenous) cell migration, and/or providing new (exogenous) cells, with varying degrees of three-dimensional (3D) architecture; and (3) neurite pathfinding (generally axonal) to restore local connections and/or reconstruct long-distance circuitry. The ultimate goal of these therapies is to prevent cell/axonal loss, promote healing, reconstruct lost neural architecture/connections, and ultimately facilitate functional recovery following nervous system disorders.

34.2. Nervous system function, anatomy, and cellular architecture

Effective strategies to facilitate brain reconstruction require an appreciation of the sophisticated architecture (spanning micro- to macroscales), multicellular composition, and unique functional domains found across the nervous system [1,3]. In total, the nervous system serves as the body’s communication and control network. A complex collection of specialized cells gathers and processes information from various sources, routes the information to the appropriate locations, and generates responses to the information to elicit a range of physiological functions [1,4,5]. The information may relate to the external environment, the body’s position and orientation in space, or various tissue, organ, and system-level phenomena [1,5]. Functionally, the nervous system is subdivided into the somatic (associated with conscious control such as movement) and the autonomic (responsible for unconscious/involuntary behavior such as breathing or digestion) nervous systems [1,6]. Anatomically, the nervous system has two primary components—the central nervous system (CNS), comprises the brain and spinal cord, and the peripheral nervous system, encompassing the nerves that bridge the CNS to the rest of the body [1].

The focus of this chapter is on the brain, which serves as the primary mammalian processing and coordination center. Information about the environment (i.e., external stimuli) and the body’s structural and functional behavior (e.g., proprioception) is encoded as electrical signals that are transmitted along axons—long fibers or tracts projecting from neurons—for feature extraction, processing, and integration and redirection to appropriate subnetworks within the brain [1]. S...

Table of contents

• Cover image
• Title page
• Table of Contents
• Copyright
• List of contributors
• Foreword
• Preface
• Acknowledgment
• Part Six. Neural tissue engineering scaffolds
• Part Seven. Skin tissue engineering scaffolds
• Part Eight. Scaffolds for reproductive system
• Part Nine. Scaffold for respiratory tissue engineering
• Part Ten. Scaffolds for urinary system
• Part Eleven. Scaffolds for digestive system
• Part Twelve. Ocular tissue engineering scaffolds
• Part Thirteen. Tissue engineering scaffolds in endocrinology and metabolism
• Index