Bone Substitute Biomaterials

K. Mallick

• Publisher: Woodhead Publishing
• Year: 2014
• Print ISBN: 9780857094971
• eBook ISBN: 9780857099037
• Topic: Medicine
• Subtopic: Medical Technology & Supplies

Bone substitute biomaterials are fundamental to the biomedical sector, and have recently benefitted from extensive research and technological advances aimed at minimizing failure rates and reducing the need for further surgery. This book reviews these developments, with a particular focus on the desirable properties for bone substitute materials and their potential to encourage bone repair and regeneration. Part I covers the principles of bone substitute biomaterials for medical applications. One chapter reviews the quantification of bone mechanics at the whole-bone, micro-scale, and non-scale levels, while others discuss biomineralization, osteoductivization, materials to fill bone defects, and bioresorbable materials. Part II focuses on biomaterials as scaffolds and implants, including multi-functional scaffolds, bioceramics, and titanium-based foams. Finally, Part III reviews further materials with the potential to encourage bone repair and regeneration, including cartilage grafts, chitosan, inorganic polymer composites, and marine organisms. - Provides a detailed and accurate overview of the bone substitute biomaterials, a fundamental part of the biomaterials and biomedical sector - Provides readers with the principles of bone substitute biomaterials - Reviews biomaterials for bone regeneration

Part I

Properties of bone substitute biomaterials in medicine

Outline

1 Bone substitutes based on biomineralization

2 Experimental quantification of bone mechanics

3 Osteoinductivization of dental implants and bone-defect-filling materials

4 Bioresorbable bone graft substitutes

1

Bone substitutes based on biomineralization

S. Sprio, M. Sandri, S. Panseri, M. Iafisco, A. Ruffini, S. Minardi and A. Tampieri, Institute of Science and Technology for Ceramics, ISTEC–CNR, Italy

Abstract:

The establishment of new and effective approaches to regenerative medicine requires a high interdisciplinary character between materials science, biology and surgery; this new paradigm is today fostering large advances in materials science and a more clear definition of the key aspects related to bone tissue regeneration. In this respect new bio-inspired approaches for the synthesis of biomaterials, such as in vitro biomineralization, enables the production of a new generation of smart, multifunctional and stimuli-responsive biomimetic materials for hard tissue regeneration. Among these advances, the implementation of new functionalities triggered by external magnetic signals may open the way to new therapeutic approaches to increase the regenerative potential of the scaffold, also reducing invasiveness during the implantation surgery.

Key words

biomimesis; bone regeneration; osteochondral regeneration; biomineralization; stimuli-responsive; magnetism

1.1 Introduction

Nowadays, the development of novel materials and devices exhibiting smart behaviour and able to function as complex systems is an emerging and increasingly crucial necessity. For this reason, over the last decade, materials science has gradually evolved into a new interdisciplinary topic, which includes nanotechnology and, more recently, also the life sciences. Indeed, there is a growing consciousness of the limitations of conventional manufacturing methodologies in synthesizing highly complex devices, due to the lack of cost- and labour-effectiveness; moreover, worries about process reproducibility strongly increase with device complexity, so that the manufacture of such devices at reasonable costs and at adequate production scales for their widespread use is a serious concern.

In this respect, new approaches of fabrication are being explored, in particular by devoting special attention to the reproduction of complex structures following the examples found in nature. Such materials are of great interest due to their versatile applications in many application areas, spanning the biomedical through energetics to the environment, health and safety (EHS) fields. In particular, the new approaches of regenerative medicine require the development of materials displaying complex, non-homogeneous, physical–chemical features and structure, in compliance with the complex nature of human tissues and organs, and being able to exhibit smart behaviour, to follow the ever changing physiological environment of living organisms.

For a decade, one of the most amazing natural processes, biomineralization, was reproduced in the laboratory to develop materials and devices mimicking multifunctional anatomical regions. Biomineralization is a complex ensemble of concomitant phenomena, driving the development of complex biological structures, associating highly organized protein/carbohydrate matrices which function as templates for the nucleation and organization at the nanoscale of inorganic nanostructured phases (Berman et al., 1993; Lowenstam and Weiner, 1989). The formation and organization of these structures occurs through information exchange at the molecular level between the organic and inorganic component. Such a process is able to induce chemical–physical and structural complexity not achievable by any conventional manufacturing process as well as outstanding properties including the capacity to intelligently respond to the environmental stimuli, also including the ability of self-renewal and self-regeneration upon limited damages.

The formation of human hard tissues is governed by self-assembly and organization of collagen molecules in a complex 3D structure, which acts as a template for simultaneous mineralization with nanocrystalline apatite. The heterogeneous nucleation, growth and specific orientation of the mineral nanograins are mediated by various chemical, physical, morphological and structural control mechanisms, controlled by the organic matrix at different size levels; these unique features influence cell behaviour and phenotype development and drive the formation/organization of living tissues.

This chapter illustrates the lab-based biomineralization processes, settled to synthesize hybrid hydroxyapatite (HA)/collagen scaffolds for regeneration of bone and osteochondral tissues. The reproduction of the natural phenomena yielding new bone formation allowed synthetic hybrid composites to be obtained, expressing high biomimesis and resulting in very good regenerative ability. Such devices were developed and brought to clinical application and the current research is now devoted to improving the behaviour of the existing materials to extend the field of application to regeneration of large, load-bearing, multifunctional anatomical regions. In this respect, the chapter will introduce new approaches to develop composite polymeric matrices able to mediate biomineralization processes, to achieve hybrid constructs with improved mechanical and elastic behaviour. Next, we will outline the new perspectives which may be opened up by new chemical/biochemical functionalization enabling the scaffolds to trigger specific cell phenotypes and/or to function as intelligent drug delivery systems capable of releasing bioactive molecules and drugs upon establishment of specific physiological conditions, such as inflammatory states. In conclusion, an overview on potential future trends in this field will explore the intriguing potential offered by novel superparamagnetic biohybrid devices. The recent development of a bioactive superparamagnetic HA opens new possibilities to produce scaffolds with remote controlling, avoiding any cytotoxic effect. The application of local weak magnetic fields may provide a new tool to assist and direct cell behaviour, thus increasing the osteogenic and angiogenic capacity of the new bone scaffolds and this may open new perspectives in regenerative medicine.

1.2 Key aspects driving the regeneration of hard connective tissues

The new concepts of regenerative medicine are intended to provide new innovative therapies able to restore the original functions of diseased tissues, with beneficial secondary effects of reducing healthcare costs, the duration of hospital stay as well as to significantly reduce the physical and psychological pain of patients. However, technological limitations still exist which weaken the establishment of regenerative therapies, since the regeneration of organized and multifunctional anatomical tissues (like osteocartilaginous regions) requires scaffolds able to show compositional and structural complexity. In fact, to trigger the correct cascade of biological events that lead to tissue regeneration, cells need to be exposed to an adequate array of chemical–physical, structural and morphological signals whose presentation follows precise spatial and temporal patterns. This requires the establishment of suitable strategies in designing scaffolds for bone or osteochondral tissue regeneration so as to reproduce such signals and provide cells with information compelling them to express specific phenotypes.

The structural organization of living tissues presents nano-sized elements hierarchically organized on different scale levels which allow them to exist and function with the minimum energy expenditure and an optimization of the available resources (Meyers, 2008). Native organisms form and evolve following a bottom-up scheme, able to self-adapt at all levels of hierarchy to the different modifications of the surrounding environment, partly due to its initial non-specificity (Fratzl and Weinkamer, 2007). Following this scheme, nano-sized natural elements spontaneously assemble to form structures with a high level of organization, up to the macroscopic scale, upon exchange of information at a molecular scale that regulate the formation and organization of mineral phases in contact with a protein-based matrix acting as promoter of heterogeneous nucleation. In the case of the formation of hard connective tissues such as bone and osteochondral tissue, a collagen-based matrix, also containing non-collagenous macromolecular chains, forms upon extrusion by fibroblast cells and spontaneous self-assembly from nanofibrils to larger fibres. During this process, the heterogeneous nucleation of nanonuclei in the mineral phase takes place through activation of several control mechanisms, thus forming three-dimensional hybrid (organic–inorganic) composites showing superior physicochemical and texturing properties. In particular, chemical factors mediate the precipitation of ions naturally present in the extracellular environment (e.g., Ca²⁺, PO₄³⁻, Mg²⁺, CO₃²⁻, K⁺, Na⁺, SiO₄⁴⁻), which concur to form nanonuclei of the mineral phase in correspondence of specific loci, situated at the gaps left by the staggering of tropocollagen molecules (Olszta et al., 2007; Tampieri et al., 2005, 2011). The mineral phase is a nanocrystalline HA (Ca₁₀(PO₄)₆(OH)₂), though the resulting Ca:P ratio is less than 1.67, that is, a calcium-deficient HA (LeGeros and LeGeros, 1984; Rey, 1998). The charge imbalance provoked by the calcium vacancies is partially restored by the incorporation of several foreign ions in the crystal sites of calcium (e.g., Mg²⁺, K⁺, Na⁺, Sr²⁺,) and phosphate (e.g., CO₃²⁻, SiO₄⁴⁻). The lack of calcium and the presence of foreign ions concur to hamper the crystallization of the mineral phase, thus resulting in a poorly crystalline phase (in comparison with HA phases synthesized by conventional wet methods) with nano-sized crystals, characterized by a much higher specific surface and thus high solubility and bioavailability at physiological pH (Gomez-Morales et al....

Table of contents

• Cover image
• Title page
• Table of Contents
• Copyright
• Contributor contact details
• Woodhead Publishing Series in Biomaterials
• Dedication
• Part I: Properties of bone substitute biomaterials in medicine
• Part II: Biomaterial substitute scaffolds and implants for bone repair
• Part III: Biomaterials for bone repair and regeneration
• Index