Octacalcium Phosphate Biomaterials

Understanding of Bioactive Properties and Application

Gerard Insley, Osamu Suzuki

• Publisher: Woodhead Publishing
• Year: 2019
• Print ISBN: 9780081025116
• eBook ISBN: 9780081025123
• Topic: Biological Sciences
• Subtopic: Biotechnology
• Index: Biological Sciences

Octacalcium Phosphate Biomaterials: Past, Present and Future is a comprehensive study of octacalcium phosphate (OCP), a next generation biomaterial for bone regeneration. By focusing both on fundamental research and the use of OCP as a scaffold material, this book explores its potential to deliver improved clinical results. Early chapters in the book discuss OCP's effects on bone cell activity, cellular interactions and their role in bone formation, repair and replacement. Later chapters cover topics such as drug delivery, synthesis methodologies and future analysis techniques. This will be an invaluable and unique resource for researchers, clinicians, students and industrialists in the area of orthopedics and dentistry.OCP is known to be a pre-cursor to hydroxyapatite in the human biomineralization process that forms bone and tooth enamel. Research studies that have emerged in recent years suggest OCP's tremendous potential as a bioactive material.- Contains comprehensive, up-to-date information on the basic science, including physical, chemical and biological properties- Presents the clinical potential of octacalcium phosphate biomaterials- Provides a reference point for new research and increased activity in the area of next generation smarter biomaterials for hard tissue repair and regeneration

1

Evolution of octacalcium phosphate biomaterials

Osamu Suzuki, Division of Craniofacial Function Engineering, Tohoku University Graduate School of Dentistry, Sendai, Japan

Abstract

In this chapter the major findings and advances in octacalcium phosphate (OCP) biomaterials were summarized through discussion of factors for selection of biomaterials used in bone tissue repair and the fundamental properties of these biomaterials, particularly in terms of enhancing bone regeneration and clinical applications. The first hypothesis was that biominerals such as OCP, which is presumed to be a precursor to bone apatite crystals, could be actively involved in physiological intramembranous bone development. As such, introduction of synthetic OCP in active biomineralization sites could facilitate additional new bone formation for bone tissue derived from the OCP-like phase. The first experiment to test this hypothesis produced the finding that synthetic OCP placed onto mouse calvaria can be converted to the apatitic phase and induce the early appearance of new bone tissue more readily than other calcium phosphate materials including amorphous calcium phosphate (ACP) or nonsintered hydroxyapatite (HA) materials. Subsequent studies found that OCP induces physicochemical reactions during the hydrolysis of OCP to Ca-deficient HA and enhances osteoblastic differentiation and formation of osteoclasts from bone marrow cells. OCP-based materials have been critical in the development of successful clinical applications that promote bone augmentation.

Keywords

Octacalcium phosphate; biomineralization; hydrolysis; Ca-deficient hydroxyapatite; osteoconduction

1.1 Introduction

Octacalcium phosphate (OCP, Ca₈H₂(PO₄)₆·5H₂O) can be used as a bone substitute material due to its highly osteoconductive and bioactive properties [1–3]. This chapter provides an introduction to and overview of OCP biomaterials. The driving forces behind selection and use of OCP for bone tissue repair, significant research findings, and clinical applications of OCP, as well as factors that are crucial for novel bone healing treatments involving OCP are also discussed.

1.2 Selection of suitable materials to promote bone tissue repair

1.2.1 Octacalcium phosphate: materials science and relevance for biomaterials

The crystal structure of OCP determined by Dr. Brown revealed an alternating stack of apatite and hydrated layers [4]. The refined OCP structure further studied by Mathew et al. showed the nonstoichiometric composition regarding hydrogen in the structure [5]. Tung et al. determined the solubility of OCP from 4°C to 37°C that included physiological temperatures and introduced a method to minimize OCP hydrolysis during the measurement [6]. OCP is a precursor of hydroxyapatite (HA) that can be formed from a supersaturated calcium and phosphate solution [7] and thus has been considered a precursor to bone apatite crystals [4,8]. The plate-like morphology also supports OCP as a bone apatite mineral precursor [8]. A recent study showed that bone crystals can induce OCP formation through citric acid incorporation [9]. Despite these findings, whether OCP is in fact a precursor to bone apatite crystals remains controversial [10]. The detection of OCP in human dentin [11], but not bone, may be due to one or more factors: (1) biological apatite crystals, especially newly formed crystals, will likely be very small [12]; (2) a crystal phase referred to as the OCP-like phase may be present that has similar solubility as OCP [13] but not the primary X-ray characteristics such that the X-ray diffraction (XRD) patterns are similar to that of the apatitic phase [7,13]; and (3) newly formed bone crystals are composed of low-crystalline nano-HA [14]. In solution chemistry the HA forms via an OCP-like phase hydrolyzed from amorphous calcium phosphate (ACP) that precipitates from a supersaturated metastable calcium phosphate solution at physiological pH [7]. Indeed, chemical analyses indicated that human serum is almost saturated with respect to OCP [15,16], which does not exclude the possible hydrolysis of OCP under supersaturation with respect to HA in a physiological setting. Furthermore, the cluster structure of OCP is maintained throughout HA formation [17] and biomineralization [18]. In human enamel the presence of OCP was evidenced by a central dark line structure [19], and in developing mice, it was present at the calvaria suture [20], although whether this finding in mice actually reflects the presence of OCP is unclear [10,21]. Nonetheless, from the perspective of biomaterial applications, OCP likely has essential roles during biomineralization and bone formation. As such, there is a growing body of information regarding the usefulness of OCP as a biomaterial [1,2,22–25], particularly given that the superior osteoconductive property of OCP was first found in an onlay graft of OCP granules on mouse calvaria in a comparison with the performance of various nonsintered calcium phosphate materials [22].

1.3 Major findings and advances

1.3.1 Hypothesis and experimental support for the biological significance of octacalcium phosphate

During bone mineralization, ACP, OCP, and dicalcium phosphate dihydrate (DCPD) are thought to be precursors for the formation of bone apatite crystals based on the crystal structure and chemical properties of these compounds in a physiological setting [16,26–28]. From the perspective of biomaterials, one hypothesis contends that OCP may be actively involved in bone formation processes but does not act simply as a crystalline substrate that is intermediate to bone apatite crystals [22]. However, a second hypothesis states that bone formation may be more efficient if synthetic OCP is placed directly at the site of bone formation [22,23]. To test this latter hypothesis an experiment was conducted to assess the appearance of bone tissue around implanted materials including OCP and the crystallized calcium phosphate form of HA [22]. For that study, DCP (the anhydrous form of DCPD), ACP (Ca/P molar ratio 1.5), OCP, and stoichiometric HA (Ca/P molar ratio 1.67) or nonstoichiometric Ca-deficient HA having a lower Ca/P molar ratio (1.5) were wet synthesized. The HA materials were obtained directly without any precursor phases. The granule form of the calcium phosphate materials was implanted onto the subperiosteal region of mouse calvaria, and the rate of bone tissue appearance and changes in the crystal phase of the implanted materials were examined in undecalcified specimens over the subsequent 15 weeks by in situ microbeam XRD analysis of the corresponding area with implanted OCP [22]. Although bone tissue appeared regardless of which material was implanted, the precursor materials DCP, ACP, and OCP promoted earlier appearance of bone tissue compared to that of HA materials (from 5 weeks). In particular, among the precursors, OCP had the earliest time of bone tissue appearance (at 1 week compared to 3 weeks for DCP and ACP). Microbeam XRD indicated that while the HA phases were maintained, OCP and ACP tended to convert to HA from between 1 and 5 weeks, whereas DCP tended to convert to HA slowly until 15 weeks. These results suggested that the introduction of synthetic OCP positively promotes bone formation [22]. These findings that supported this hypothesis formed the foundation for our subsequent studies on the use of OCP in biomaterials and research into the mechanisms by which OCP enhances bone formation.

1.3.2 Initial evidence that octacalcium phosphate provides a nucleation site for bone deposition

Implantation of OCP granules having a diameter of several hundred micrometers and consisting of an aggregate of OCP crystals several micrometers in length onto the subperiosteal region of mouse calvaria resulted in osteoblasts localizing to the OCP granule surface to initiate bone deposition and also new bone ingrowth from existing original bone as shown by histological and ultrastructural examinations [22,29,30]. Transmission electron microscopy of the ultrastructure of decalcified specimens indicated that osteoblasts attached directly to the OCP surface to form bone matrix [22,29] and that the tissue structure surrounding the OCP implant comprised fine filaments and granular materials (noncollagenous proteins) that were highly similar to the components of the starting locus of intramembranous osteogenesis or so-called bone nodules [22,31]. Such bone nodules were later assigned as the calcospherite, a mineralized structure that forms from osteoblast secretions after initial mineral deposition within the matrix vesicle [31–33]. Sec...

Table of contents

• Cover image
• Title page
• Table of Contents
• Copyright
• List of contributors
• About the editors
• Preface
• 1. Evolution of octacalcium phosphate biomaterials
• 2. Octacalcium phosphate effects on the systemic and local factors that regulate bone-cell activity
• 3. Functionalization of octacalcium phosphate for bone replacement
• 4. The influence of sterilization on octacalcium phosphate for clinical applications
• 5. Bioactivity and effect of bone formation for octacalcium phosphate ceramics
• 6. Novel scaffold composites containing octacalcium phosphate and their role in bone repair
• 7. Synthesis methodologies options for large-scale manufacturer of octacalcium phosphate
• 8. Synthesis and physical chemical characterizations of octacalcium phosphate–based biomaterials for hard-tissue regeneration
• 9. Calcium orthophosphate (CaPO4)–based bone-graft substitutes and the special roles of octacalcium phosphate materials
• 10. Development and clinical application of octacalcium phosphate/collagen composites
• 11. Modification of octacalcium phosphate growth by enamel proteins, fluoride, and substrate materials and influence of morphology on the performance of octacalcium phosphate biomaterials
• Index