Bio-inspired Materials for Biomedical Engineering

Anthony B. Brennan, Chelsea M. Kirschner, Anthony B. Brennan, Chelsea M. Kirschner

• Publisher: Wiley
• Year: 2014
• Print ISBN: 9781118369364
• eBook ISBN: 9781118843437
• Edition: 1
• Topic: Biological Sciences
• Subtopic: Biotechnology
• Index: Biological Sciences

This book covers the latest bio-inspired materials synthesis techniques and biomedical applications that are advancing the field of tissue engineering.  Bio-inspired concepts for biomedical engineering are at the forefront of tissue engineering and regenerative medicine. Scientists, engineers and physicians are working together to replicate the sophisticated hierarchical organization and adaptability found in nature and selected by evolution to recapitulate the cellular microenvironment.  This book demonstrates the dramatic clinical breakthroughs that have been made in engineering all four of the major tissue types and modulating the immune system.

Part I (Engineering Bio-inspired Material Microenvironments) covers Bio-inspired Presentation of Chemical Cues, Bio-inspired Presentation of Physical Cues, and Bio-inspired Integration of Natural Materials.

Part II (Bio-inspired Tissue Engineering) addresses tissue engineering in epithelial tissue, muscle tissue, connective tissue, and the immune system.

PART I
Engineering Bio-inspired Material Microenvironments

CHAPTER 1
ECM-Inspired Chemical Cues: Biomimetic Molecules and Techniques of Immobilization

Roger Y. Tam and Shawn C. Owen

The Donnelly Centre for Cellular and Biomolecular Research, Department of Chemical Engineering and Applied Chemistry, Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada

Molly S. Shoichet

The Donnelly Centre for Cellular and Biomolecular Research, Department of Chemical Engineering and Applied Chemistry, Institute of Biomaterials and Biomedical Engineering, Department of Chemistry, University of Toronto, Toronto, Ontario, Canada

1.1 Introduction

The extracellular matrix (ECM) is a complex environment that provides chemical and physical support to cells, Figure 1.1 [1,2]. The composition of native ECM differs based on its location within the body [3–6], but it is generally comprised of proteins (fibronectin, laminin, and collagen), polysaccharides (hyaluronan and chondroitin sulfate proteoglycans [CSPGs]) and various growth factors [6]. Components of the ECM play important roles in controlling cell function. Molecules such as collagen [7] and elastin [8] function as the structural scaffold to support cell growth, whereas fibronectin, laminin, glycosaminoglycans (GAGs), and growth factors act as ligands to promote cell adhesion, proliferation, differentiation, and migration [9].

Figure 1.1 The complex 3-D cellular environment provides mechanical and biochemical signals that guide cell function. The components of the ECM dictate the stiffness of matrix and the types of cell–matrix interactions. The matrix composition determines the ease with which nutrients diffuse through tissues and the ability with which cells migrate through the matrix. Nonstructural factors such as cell density, cell–cell interactions, and bound or secreted signaling proteins are important in guiding cell differentiation and function. (Reproduced with permission from Owen, S.C., Shoichet, M.S. Journal of Biomedical Materials Research A 2011, 94A(4). Copyright 2013 Wiley Periodicals Inc.)

Cells can remodel the ECM in a dynamic fashion [9,10]. For example, cells can secrete proteases that can degrade the ECM to promote cell migration, which is important in tissue repair, such as neuroblast migration following traumatic brain injury (TBI) [11], as well as in disease states, such as cancer metastasis [12]. Cells can also secrete their own ECM molecules on top of the existing ECM to provide new cues affecting both self and neighboring cells [10].

The increased understanding of the role of native ECM on cellular function and interactions has resulted in extensive research into biomimetic materials for applications in tissue engineering [13,14]. Hydrogels represent a class of biomaterials that have been used for this purpose. These highly hydrated polymers provide structural scaffolds and permit diffusion of molecules throughout. Matrigel® (BD Biosciences, San Jose, CA), a decellularized ECM derived from the Engelbreth–Holm–Swarm (EHS) mouse sarcoma, is a common hydrogel used to mimic the three-dimensional (3-D) properties of the ECM [15]. This material has been shown to promote various bioactivities such as cell adhesion, differentiation, viability, and invasion in a variety of cell types; however, for studies that require a more defined 3-D environment (such as those for mechanistic elucidation studies), the use of Matrigel® is nonideal as it is ill-defined in composition and the results are often difficult to reproduce. As such, a bottom-up approach is desirable where researchers begin with a blank palette in terms of cellular interactions and then paint in desirable features, such as cell adhesion, proliferation, and migration through both chemical and physical designs. Efforts to synthesize biomimetic ECMs with defined components were significantly advanced by the discovery that short peptide sequences (e.g., RGD, YIGSR, IKVAV, etc.), derived from native ECM proteins (fibronectin and laminin, respectively), promote cell adhesion and outgrowth. It was shown that RGD interacted with extracellular integrin receptors with affinity similar to that of native fibronectin [16]. Since this discovery, a large number of studies have been conducted to immobilize this and other biomimetic sequences to various biomaterials with the intention of promoting cell adhesion on nonadherent surfaces and biomaterials, thereby increasing the posttransplantation cell viability in tissue regeneration applications, and studying cell behavior in model biomimetic systems.

This chapter is focused on recent advances in the techniques used to incorporate ECM-inspired chemical signaling molecules into different hydrogels, and their effects on cellular interactions in 3-D. While similar approaches are used in multiple areas of biology, we highlight many examples applicable to neurobiology.

1.2 Development and Immobilization of Biomimetic Cues in 3-D Biomaterials

The discovery that short peptide sequences showed comparable activity to their respective native ECM proteins from which they were derived has resulted in significant efforts to design peptide-modified biomaterials with which to study cellular interactions [17,18]. Biomaterial modification with these peptide sequences (typically 3–10 amino acids) results in inherently better-defined systems than the corresponding protein-modified systems due to the shorter sequence length and resulting 3-D structure. To take full advantage of ligand-containing biomaterials to study complex cellular interactions, it is imperative that the ligand is chemically conjugated to the biomaterial in a reproducible and specific manner in order to optimize cellular interaction. For example, conjugation at the active site of the peptide may diminish receptor binding and therefore limit bioactivity. An important consideration in designing biomimetic molecules is to include a specific functional group that has a selective chemical reactivity toward the material to which it will be conjugated.

The emergence of click chemistry as a method to conjugate molecules to biomaterials has proved to be a powerful technique to allow efficient conjugation with both defined chemical reactivities and orientation [19–22]. These orthogonal reactions are specific and occur with high yield and efficiency. While detailed discussion about this topic is beyond the scope of this chapter, Figure 1.2 shows a brief summary of different conjugation reactions that have been used to immobilize various peptides and proteins to biomaterials. The following se...

Table of contents

• Cover
• Table of Contents
• Series page
• Title page
• Copyright page
• Contributors
• Preface
• Introduction
• PART I: Engineering Bio-inspired Material Microenvironments
• PART II: Bio-Inspired Tissue Engineering
• Supplemental Images
• Index
• End User License Agreement