Regenerative Engineering of Musculoskeletal Tissues and Interfaces

Syam Nukavarapu, Joseph Freeman, Cato Laurencin

• Publisher: Woodhead Publishing
• Year: 2015
• ISBN:
  9781782423140
• Topic: Biological Sciences
• Subtopic: Biotechnology
• Index: Biological Sciences

Repair and regeneration of musculoskeletal tissues is generating substantial interest within the biomedical community. Consequently, these are the most researched tissues from the regeneration point of view. Regenerative Engineering of Musculoskeletal Tissues and Interfaces presents information on the fundamentals, progress and recent developments related to the repair and regeneration of musculoskeletal tissues and interfaces. This comprehensive review looks at individual tissues as well as tissue interfaces. Early chapters cover various fundamentals of biomaterials and scaffolds, types of cells, growth factors, and mechanical forces, moving on to discuss tissue-engineering strategies for bone, tendon, ligament, cartilage, meniscus, and muscle, as well as progress and advances in tissue vascularization and nerve innervation of the individual tissues. Final chapters present information on musculoskeletal tissue interfaces.

• Comprehensive review of the repair and regeneration of musculoskeletal individual tissues and tissue interfaces
• Presents recent developments, fundamentals and progress in the field of engineering tissues
• Reviews progress and advances in tissue vascularization and innervation

Part One

Basic elements of musculoskeletal tissue engineering

Outline

1. Biomaterials and scaffolds for musculoskeletal tissue engineering

2. Cells for musculoskeletal tissue engineering

3. Growth factors for musculoskeletal tissue engineering

4. Mechanical forces in musculoskeletal tissue engineering

1

Biomaterials and scaffolds for musculoskeletal tissue engineering

E. Francois¹, D. Dorcemus^2,3, and S. Nukavarapu^{2,3,4,5 1}School of Medicine, Meharry Medical College, Nashville, TN, USA ²Institute for Regenerative Engineering, University of Connecticut Health Center, Farmington, CT, USA ³Biomedical Engineering, University of Connecticut, Storrs, CT, USA ⁴Materials Science and Engineering, University of Connecticut, Storrs, CT, USA ⁵Orthopaedic Surgery, University of Connecticut Health Center, Farmington, CT, USA

Abstract

This chapter reviews current research being undertaken in biomaterials and scaffolds for musculoskeletal tissue repair and regeneration. The bulk of the chapter is focused on natural and synthetic biodegradable biomaterials, physical property requirements and biomaterial fabrication into three-dimensional and interconnected porous structures for the regeneration of musculoskeletal tissues (bone, tendon, ligament, etc.), as well as tissue interfaces (bone/cartilage, bone/tendon, etc.). Because biomaterials and scaffolds serve as a principal component of tissue engineering, it is important to develop matrices that serve as functional replacements for the musculoskeletal tissues and for better and clinically relevant regeneration. The progress made and the challenges remaining to be addressed are reviewed toward the end.

Keywords

Advances and challenges; Biomaterials; Natural; Scaffolds; Synthetic; Tissue engineering

1.1. Introduction

Biomaterials, along with stem cells and signaling molecules, serve as principal components of tissue engineering. Three-dimensional (3D) biomaterial structures with interconnected pores (i.e., scaffolds) act as conduits for cell attachment, growth and infiltration, and tissue development. Scaffold structures developed using a variety of biomaterials play an important role in the repair and regeneration of musculoskeletal tissues as well as tissue interfaces (Nukavarapu, Liu, Deng, Oyen, & Tamerler, 2013).

As it pertains to the musculoskeletal system, tissue engineering aims to develop treatment strategies for a wide array of orthopedic tissues, with prime examples being bone, cartilage, ligament, tendon, and skeletal muscle (Cooper et al., 2007; Hutmacher, 2000; Levenberg et al., 2005; Mikos et al., 2006). The selection of biomaterials involves the use of both natural and synthetic biocompatible and biodegradable materials that are formed into 3D scaffolds. After these biomaterials are fabricated and implanted into the host, their interaction with native cells and growth factors sets forward the initiation of tissue regeneration throughout the 3D pore network. Biodegradable scaffolds exemplify this dynamic interplay; scaffolds provide a perfect 3D architecture for body repair mechanisms and new tissue formation. Ideally, biodegradable scaffolds are designed with degradation rates matching the new tissue formation rate. Furthermore, their biodegradable properties allow these scaffolds to be slowly resorbed by the surrounding tissue, and ultimately they are completely replaced with newly regenerated tissue. As a result, the repair site remains free of any residual polymer (Amini, Laurencin, & Nukavarapu, 2012; Langer & Vacanti, 1993; Laurencin et al., 1999; Nukavarapu, Wallace, Elgendy, Lieberman, & Laurencin, 2011).

The ultimate aim of tissue engineering is to regenerate the patient’s own tissue without leaving behind permanent implants. The great advantage of this approach is that it negates the need for replacement surgeries, and permanent implants, infection, or failure, which are many of the disadvantages of the conventional repair strategies. In all, the objective of tissue engineering is to repair/regenerate biologically sound tissues via the use of biodegradable biomaterials and scaffolds with or without the use of cells and/or signaling molecules, while overcoming the many disadvantages associated with the conventional repair strategies.

1.2. Biomaterials

Biomaterials are materials that can be used as implants or parts of implants, which treat or augment any tissue, organ, or function of the body. Previously, biostable and inert materials were considered ideal biomaterials for use in medicine. Popular examples are the metallic biomaterials and implants used in orthopedics, gutta-percha root-canal filler in dentistry, as well as the silicone gel used for breast implants (Ratner, Hoffman, Schoen, & Lemons, 2012). These stable biomaterials or implants are designed to serve the intended function causing minimal to no interaction with the surrounding tissues or bodily fluids. Today the concept of an ideal biomaterial has changed, especially with the invention of biodegradable biomaterials. Biodegradable or absorbable biomaterials have the potential to clear from the body after serving their intended function. The invention of biodegradable biomaterials has led to the development of new fields, such as tissue engineering and drug delivery. Biodegradable sutures and fibrin-based tissue sealants are some of the notable examples of biodegradable biomaterials. Now, biomaterials encompass both the biostable and bioabsorbable material groups.

1.2.1. Biodegradable biomaterials

For certain applications, biodegradable biomaterials are advantageous over the traditional (biostable) biomaterials because implants, made out of biodegradable materials, have the ability to disintegrate into smaller fragments and clear from the body, after their intended use. Polyesters were the first family of biodegradable biomaterials that were found to break down into smaller fragments, lactic acid and/or glycolic acid, based on the initial polymer composition (Gliding & Reed, 1979). Since then, several synthetic and natural biomaterials, with diverse compositions, have been synthesized and characterized as biodegradable biomaterials. While all the materials will degrade eventually, only the polymers with therapeutically relevant degradation rates are considered as biodegradable or bioabsorbable biomaterials. Hydrolytic degradation and enzyme-assisted degradation are the two dominant mechanisms by which the bioabsorbable polymeric materials degrade. Polymer composition, presence of hydrophilic functional groups, and polymer molecular weight are some of the factors that largely control the biomaterial degradation rate (Barrows, 1986; Middleton & Tipton, 2000; Pietrzak, Sarver, & Verstynen, 1997).

1.2.2. Biomaterials for musculoskeletal tissue engineering

Biomaterials, or the scaffolds made out of biomaterials, are an important basic component of tissue engineering. Tissue engineering generally involves biomaterials, cells, and/or signaling molecules as the fundamental blocks for tissue repair and regeneration. Although initial efforts in tissue engineering were focused on skin tissue regeneration, efforts for musculoskeletal tissue engineering became very prominent due to the large number of musculoskeletal defect repairs performed annually in the United States and worldwide. Traditionally, autografts (derived from the same patient) and allografts (derived from cadavers) have been used in musculoskeletal defect repair. Although these grafts possess tissue structure, composition, and mechanical properties similar to those of the host tissue, limited tissue availability with autografts and disease transmission associated with allografts necessitate the need to develop alternative graft options for musculoskeletal tissue defect repair (Delloye, Cornu, Druez, & Barbier, 2007; Seiler & Johnson, 2000). Although the search is on for better graft substitutes, biomaterials and biomaterials-based strategies show the potential to be developed into tissue-engineered grafts for musculoskeletal defect repair, restoration, and regeneration.

Musculoskeletal tissues comprise bone, cartilage, tendon, ligament, muscle, meniscus as well as bone–cartilage, bone–tendon, bone–ligament, bone–meniscus, and muscle–tendon interfaces. This tissue system supports mainly body shape, structure, and locomotion. Musculoskeletal tissues display a range of mechanical properties; to mimic their mechanical characteristics, biomaterials of various types with different physical properties (hard, flexible, elastic, etc.) are being developed. In this chapter, we will provide an overview of biomaterial types considered, scaffold fabrication methods, as well as some strategies employed to utilize biomaterials and scaffolds for musculoskeletal tissue engineering.

1.2.3. Synthetic and natural polymers as biomaterials

There are approximately three million musculoskeletal procedures performed in the United States annually (Desai, 2007). Because of the aging baby boomer population as well as the general increase in the rates of orthopedic procedures, investigators are forever in pursuit of novel biomaterials to meet the increased demand. A list of common synthetic and natural biomaterials proposed for musculoskeletal tissue repair and regeneration is presented in Table 1.1.

Table 1.1

Biomaterials for musculoskeletal tissue engineering (MTE)

Biodegradable polymers	Example groups	MTE application
Synthetic	Polyesters Polyure...

Table of contents

• Cover image
• Title page
• Table of Contents
• Related titles
• Copyright
• Dedication
• List of contributors
• Woodhead Publishing Series in Biomaterials
• Part One. Basic elements of musculoskeletal tissue engineering
• Part Two. Individual musculoskeletal tissues
• Part Three. Musculoskeletal tissue interfaces
• Index