Translating Biomaterials for Bone Graft

Bench-top to Clinical Applications

Joo L. Ong, Teja Guda

• Publisher: CRC Press
• Year: 2017
• ISBN:
  9781315363516
• Edition: 1
• Topic: Medicine
• Subtopic: Orthopedics

Translating Biomaterials for Bone Graft: Bench-top to Clinical Applications brings together the current translational research in bone tissue engineering, from design to application – from materials, drugs and biologic delivery used for bone graft applications to pre-clinical and clinical considerations. The book also discusses the regulatory approval pathways, which involves consideration of the class of devices; whether they are similar to existing solutions, minimal manipulation of donor tissue or completely novel materials, drugs and biologics. These considerations drive the ability to successfully transition the latest generations of bone graft materials into the clinics. Chapters come from materials scientists, clinicians, researchers, and consultants and provide a holistic understanding of the field. As such, the book is a state-of-the-art reference to bone therapies and should appeal to clinicians, scientists, as well as students interested in the current research and/or practices in the field of bone regeneration and restoration.

Part I

Introduction

1

Bone Grafting Evolution

Laura Gaviria, L. Actis, Teja Guda, and Joo Ong

CONTENTS

1.1 Introduction and Clinical Need

1.2 Past and Present of Bone Grafting in Orthopedic Surgery

1.3 Recent Progress in Bone Grafting

1.3.1 Autologous Bone Grafts

1.3.2 Allogenic Bone Grafts

1.3.3 Allograft-Based Alternatives

1.3.4 Synthetic Materials

1.3.4.1 Ceramics

1.3.4.2 Polymers

1.3.4.3 Composite Materials

1.4 Clinical Need for Engineered Bone

1.5 Overview of Bone Tissue Engineering Field

1.5.1 Requirements and Properties and Biomaterial Design

1.5.2 Incorporation of Cells

1.5.3 Growth Factors and Surface Modification

1.5.4 The Need for Vascularization

1.6 Translational Requirements

1.7 Concluding Remarks

References

1.1 Introduction and Clinical Need

Bone is a dynamic and highly vascularized tissue that provides structural support to the body by carrying major biomechanical loads and playing many roles which are essential for the body. The skeleton protects internal organs, supports muscular contraction to create motion, and acts as a stored mineral reservoir that is capable of rapid mobilization on metabolic demand.^1,2 Therefore, it is reasonable to conclude that major alterations in bone’s structure dramatically affect a patient’s health and quality of life.¹

All these functions have made bone the ultimate smart composite material, by which most of its outstanding properties are related to its dual composition: a mineralized inorganic component and a non-mineralized or organic component. The mineral component comprises about 65–70% of the bone matrix and is primarily made up of biological apatites. Representing the non-mineralized or organic component is mainly type I collagen. Several different types of proteins such as glycoproteins, proteoglycans and sialoproteins are also present in the non-mineralized component.^{1,2 and 3} This composite structure of tough and flexible collagen fibers reinforced by biological apatite is integral to achieve the characteristic compressive strength and high fracture toughness of bone.²

In general, bone has a unique regenerative capacity to heal and remodel following trauma or disease without any surgical intervention and without leaving a scar, which is especially true in younger people.^{1,2,3 and 4} However, in the case of extensive tissue damage (caused by a high-energy traumatic event, large bone resection for pathologies such as tumor or infection, or severe nonunion fractures), bone defects are unable to heal without intervention.^{2,3,4 and 5} Furthermore, musculoskeletal disorders and diseases are the second greatest cause of disability globally⁶ and are the leading cause of disability in people older than 50 years of age in the United States. The number of patients with chronic musculoskeletal diseases are 60% greater than that of the number of patients with chronic circulatory diseases and more than twice that of number of patients with all chronic respiratory diseases. Unfortunately, the cost for treating musculoskeletal diseases are also associated with many direct and indirect expenditures, and these expenditures are predicted to continue growing in the next 25 years as the worldwide population rapidly ages.^1,7 In 2006 alone, the sum of the direct and indirect expenditures related to musculoskeletal diseases was estimated to be about 7.4% of the US gross domestic product.^{7,8 and 9}

With this motivation, many bone regeneration strategies have been investigated in order to improve the patient’s quality of life and to minimize the medical and socioeconomic challenges associated with bone damage.^2,3,8 Significant bone defects require the use of bone grafts in order to fuse joints, prevent movement in the spine and extremities, repair bone in delayed unions or nonunions, repair fractures with significant bone loss, and repair bone voids caused by surgery, traumatic disease or infection.^5,10

1.2 Past and Present of Bone Grafting in Orthopedic Surgery

Orthopedic techniques and bone grafting have been practiced for thousands of years.¹¹ Some first evidence on the use of bone graft substitutes has been found in prehistoric skulls with metal plates and coconut shells in the sites of cranial defects.¹² In fact, some of them have shown evidence of xenografts with regrowth around the grafted bone.¹¹

The Egyptians were also advanced in dental and bone surgery; mummies from 656–525 BC showed evidence of orthopedic operations and prostheses that were inserted while the patients were still alive. Further analysis indicated that the prostheses and artificial limbs were made out of iron, resins and wood. Although simple in design, these solutions were efficacious and allowed the patients to live for many years after the operation. Similarly, Aztec skulls with metal plates have been found, as well as ancient documents that described the treatment of bone fractures by realigning and splinting, in addition to placing of wooden prostheses in the case of failure. Later, during 300–200 BC, ancient Greeks from the Alexandrian school studied surgery extensively and performed difficult operations such as limbs amputation and tumor resection.¹¹

Modern attempts of bone grafting started in 1668 when Job van Meekeren, a Dutch surgeon, documented the filling of a bony defect in a soldier’s cranium with a piece of skull from a dog. The surgery was successful, but the patient was excommunicated by his church because of the use of xenotransplant.^11,13,14 In order to be allowed back to his church, the patient requested that the bone graft be removed 2 years after implantation. Later, in 1820, Philips von Walter, a German surgeon, performed the first autologous graft by replacing a fragment of the cranium after trepanation.¹¹ Other examples of autografts documented in the late 1800s include the use of tibial periosteal flaps by Dr. Seydel to close a cranial defect and the use of a fibular graft by Dr. Bergmann to close a tibial defect.¹²

One of the most important contributions during the nineteenth century was made in 1861 by Leopold Ollier, a French surgeon, who studied the phenomenon of bone regeneration and described the term “bone graft” for the first time. Most importantly, Ollier postulated his theories on the possibility to regenerate bone by inducing cartilage to ossify.^11,15 By that time, most popular grafts were of autologous origin, and non-autologous grafts were not taken into consideration until 1880 when William Macewen, a Scottish surgeon, implanted a tibial allograft from one child to another.¹¹ In February 1891, Dr. A.M. Phelps of New York reported the successful insertion of a piece of bone from a dog into the tibial defect of a boy.^11,12,15

Between 1912 and 1940, an Italian surgeon by the name of Vittorio Putti did research in all the major orthopedic problems and introduced new methods and surgical instruments for the improvement of graft integration.^11,16 With more than 1600 autograft procedures documented by the early 1920s, modern tools of internal and external fixation were not yet available then and the role of vascularization in the repair process was still not clear, adding to the number of limitations and failures.^11,12 Between 1915 and 1932, Fred Houdlett Albee, an American surgeon, introduced a series of rules and principles for using bone grafts and published articles describing the 810 successful operations performed on nonunions of the limbs using autografts. By 1942, many autologous and homologous transplants had been already performed, and the fundamental concepts about immune response and storage of bone material were already known.¹¹ These new concepts established the beginning of a new era in bone grafting.

1.3 Recent Progress in Bone Grafting

1.3.1 Autologous Bone Grafts

Harvested from the patient itself, autografts has been established as the gold standard for bone grafting for many decades, offering structural support with no potential for disease transmissions or immunogenic responses.¹⁷ The most common harvesting sites for autogenous cancellous bone grafts are the iliac c...

Table of contents

• Cover
• Half Title
• Title Page
• Copyright Page
• Table of Contents
• Preface
• About the Editors
• Contributors
• Part I Introduction
• Part II Materials for Bone Graft Applications
• Part III Biologic Delivery for Bone Grafts
• Part IV Clinical Considerations
• Part V Translational Pathways for Bone Graft Development
• Index