Advances in Metallic Biomaterials

Recovery of anisotropic BAp alignment strongly depends on the regenerated portion and regeneration period, which is insufficient to reach the original level, while bone mineral density (BMD) is almost improved to its original value. This finding suggests that BMD recovers prior to the improvement of BAp alignment and the related mechanical function of the regenerated tissue. Remarkable changes in degree of anisotropic BAp orientation are also found in some pathological hard tissues including gene-defected animals developing osteoporosis, osteopetrosis, and osteoarthritis.

The bone tissue from the macro- to nano- scale level, including BAp/collagen orientation, exhibits anisotropic integrity that is closely related to mechanical adaptation. In fact, BAp/collagen alignment is among the most important bone quality indices that can be used to evaluate in vivo stress distribution, nanoscale microstructure, and the related mechanical function in various bones. Optimal design of biomaterials for bone replacement can be provided from the viewpoint of bone tissue anisotropy.

Various motions of the body trunk and extremities are performed through the joint. The interdependent aspects of joint function are stability, motion, and load distribution. Joint structure is related with the joint function. The range of joint motion depends on the joint structure, articular cartilage, and soft tissue around the joint including the ligament, tendon, and muscle. Generally, the range of motion of the body trunk is much smaller than that of the extremities. Articular cartilage is evaluated using various modalities. Especially, cartilage degeneration has been studied by magnetic resonance imaging including dGEMRIC, T2 mapping, and T1rho mapping. Pathological condition is derived from the biological abnormalities such as cartilage degeneration and synovial inflammation and from the mechanical abnormalities such as ligament rupture and meniscal injury. Joint diseases are monitored using various biochemical markers. Recently, joint instability or translation, which is thought to be causative factor of osteoarthritis, has been evaluated using several modern methods.

Examination of clinical literature tends to suggest a rather limited diversity of metals used in spinal instrumentation (Netter FH (ed) Atlas of human anatomy, 5th edn. Saunders Elsevier, Philadelphia, 2011; Yoshihara H, Spine J in press, 2013). The American Society of Materials (ASM) Materials and Processes for Medical Devices (MPMD) database shows approximately 33 different alloys used in medicine in the USA. Within this database, only about one-third are used in orthopedic applications, and in the clinical environment, these alloys are generally referred to in very general terms such as titanium, Ti6Al4V, stainless steel A316L, or cobalt-chrome, CoCrMoC. For the purpose of spinal applications, it may be convenient to consider the general alloy systems, ferrous stainless steel, titanium and its alloys, cobalt-chromium, and tantalum. From this standpoint, the characteristics along with their clinical advantages and disadvantages can be discussed. The reader is kindly guided to many excellent texts concerning specific aspects of metallurgy as well as other chapters in this book for details on specific alloy systems and their properties (Yu WD, Oper Tech Orthop 13(3):159–170, 2003; Black J, Biological performance of materials, 4th edn. Taylor and Francis, Boca Raton, 2006; Hosford WF, Physical metallurgy, 2nd edn. Taylor and Francis, Boca Raton, 2010; Narayan RJ (ed) ASM handbook: vol 23, Materials for medical devices. ASM International, Materials Park, 2012; Yahia L (ed) Shape memory implants. Springer, Berlin, 2000). It should be noted based on the following section that for all metals represented herein, in terms of clinical applications, many of the properties discussed have little effect on their selection during surgery as the medical priority is maintaining bony alignment and minimizing patient discomfort.

Basics and recent advances in blood vessel wall biomechanics are overviewed. The structure of blood vessel walls is first introduced with special reference to heterogeneity in the mechanical properties of artery walls at a microscopic level. Then basic characteristics of the mechanical properties of blood vessel walls are explained from the viewpoints of mechanical parameters used in clinical investigations, elastic and viscoelastic analysis, and effects of smooth muscle contraction. As examples of mechanical analysis of blood vessel walls, stress and strain analyses of artery walls as thin- and thick-walled cylinders, analyses considering residual stress and microscopic heterogeneity, are introduced. One of the most important topics in the blood vessel mechanics, mechanical responses and adaptations of blood vessel walls, is then discussed from the viewpoints of long- and short-term responses of artery walls to increases in blood pressure or flow. And finally, the importance of studying microscopic mechanical environment to elucidate these mechanical adaptations is pointed out.

Tooth and tooth-supporting structures are involved in the function of mastication and articulation and are classified as enamel, dentin-pulp complex, and tooth-supporting structures. The dentin-pulp complex is sorted dentin and pulp, and the tooth-supporting structures are categorized as cementum, periodontal ligament, alveolar bone, and gingiva. Tooth consists of three different types of hard tissues, such as enamel, dentin, and cementum, and soft tissue of pulp and periodontal ligament. In clinical situation, a tooth is fundamentally made of the crown that is any part of the tooth visible in the mouth and the root that is any part of a tooth not visible in the mouth. Enamel covers the crown of a tooth and is the most highly mineralized substance in the human body, which includes the highest percentage of minerals. Cementum covers the root and is connected with alveolar bone, which surrounds and supports the tooth root by intervening with periodontal ligament. Dentin-pulp complex is surrounded by enamel and cementum. Dentin is the most voluminous mineralized tissue of the tooth and is formed by odontoblast that is part of the outer surface of the pulp. Pulp also includes vascular, lymphatic, and nervous elements.

High-nitrogen austenitic stainless steel (HNS) developed in NIMS shows high strength, high corrosion resistance, and nonmagnetic properties. This material was originally developed as a resource-saving type of HNS available in the seawater. It is well known that the nickel content of HNS can be reduced with increasing nitrogen content. In addition, it was found, derivatively, that nickel-free HNS was successfully produced with further increasing the nitrogen content, which is applicable to the field of biomedical area as an anti-nickel allergy biomaterial.

In this chapter, the following items are described such as production of HNS, mechanical properties, formability of HNS, corrosion properties, and the mechanism of the improvement of corrosion properties by addition of nitrogen. Finally, as one of the applications of HNS, R&D of coronary stent is introduced in terms of biocompatibility of HNS as well as in vivo test using the stents deployed into pigs’ coronary arteries. It is found that the stent made from nickel-free high-nitrogen stainless steel shows not only very excellent biocompatibility but also outstanding restenosis suppressant effect.

Because of their excellent mechanical properties, high corrosion resistance, and high wear resistance, Co-Cr alloys have been recognized as effective metallic biomaterials and have been used as materials for dental and medical devices since a cast Co-Cr-Mo alloy, Vitallium, was developed in the 1930s. Further increases in the usage of Co-Cr alloys are still expected as well. In this chapter, first, the history and current status of biomedical Co-Cr alloys such as Co-28Cr-6Mo and Co-20Cr-15W-10Ni alloys are reviewed. Their microstructure, processing, and properties are then discussed. Control of the microstructure by optimization of chemical composition of the alloys and thermomechanical treatments is described, and newly developed processing techniques for grain refinement and newly found precipitates such as the π-phase and χ-phase are discussed. As a novel process for implant fabrication, an additive manufacturing technique using an electron beam and a laser beam is mentioned. Finally, the mechanical properties and corrosion and wear resistances of the alloys are presented, and the relationships between the microstructure and properties of the Co-Cr alloys are discussed.

The low Young’s modulus of β-type titanium alloys makes them advantageous for use in medical implant devices, as they are effective in both preventing bone resorption and promoting good bone remodeling. The development of low Young’s modulus β-type titanium alloys for biomedical applications is described herein, along with a discussion of suitable methods for even greater modulus reductions. Since there is often occasion to remove implant devices, titanium alloys suitable for removable implants are also described. It has recently been noted that although patients require low Young’s modulus titanium alloys, a high modulus is needed by surgeons. Consequently, β-type titanium alloys with a self-tunable Young’s modulus are also explored. An evaluation of the effectiveness of low Young’s modulus β-type titanium alloys in preventing stress shielding is provided, which is based on the results of animal testing. Means of enhancing the mechanical biocompatibilities of β-type titanium alloys for biomedical applications are also described along with the suitability of those β-type titanium alloys which exhibit super-elastic and shape-memory behavior. Finally, the unique behavior of some β-type titanium alloys for biomedical applications is discussed.

Physical and chemical properties of zirconium (Zr) are introduced and the features and differences from titanium (Ti) are pointed out. Zr is principally applied to the nuclear power industry because of its low thermal neutron cross section. For medical applications, a Zr alloy (Zr-2.5Nb) is used in total knee and hip replacements because of its excellent wear resistance. The dense and adherent oxide layers are formed on the surface of Zr alloy and contribute to improving its wear resistance. Zr is also promising for suppressing artifacts in magnetic resonance images, because it shows lower magnetic susceptibility than that of SUS, Co-Cr alloy, and Ti. The magnetic susceptibilities of the Zr alloys are sensitive to their phase constitutions. Magnetic susceptibility in addition to mechanical properties could be controlled by changing the composition depending on the requirements for medical devices under magnetic resonance imaging (MRI).

Porous tantalum, a novel biomaterial, was approved for use in orthopedic surgery by the Food and Drug Administration (FDA) in 1997. Several preclinical and experimental studies have demonstrated excellent biocompatibility with physical, mechanical, and tissue ingrowth properties conducive for enhanced osseointegration and superior structural integrity. Porous tantalum has high volumetric porosity (75–80 %). The modulus of elasticity of tantalum (3 Gpa) compares favorably to cancellous bone (1.2 GPa) or subchondral bone (2 GPa). Porous tantalum also has a high coefficient of friction with a high resistance to compression (50–80 Mpa) and rotational deformity (40–60 Mpa). Tantalum has been used in a wide array of clinical applications in orthopedics including primary and revision joint replacement, tumor reconstructive surgery, spine fusion, management of osteonecrosis of the femoral head, and foot and ankle surgery. Recent studies have demonstrated excellent clinical and radiographic outcomes, even in the presence of extensive bone loss in hip and knee reconstructive surgeries. Its use in spine surgeries and osteonecrosis of the hip has been associated with mixed clinical results. Further clinical studies are necessary to establish its role and refine its indications in specific orthopedic applications and determine whether the theoretical advantages of porous tantalum can provide long-term biological fixation and stability. This chapter presents a synopsis of the biomaterial properties and preclinical and clinical studies of porous tantalum in orthopedic surgery.

Niobium is a particularly attractive metal for application as a biomaterial, due to the highly inert and unreactive nature of its surface. However, mechanical property limitations have restricted the use of the material in this field. This chapter initially reviews some of the fundamental aspects of niobium biocompatibility with a particular emphasis on surface technologies such as vapour deposition, sol-gel, anodizing and boronizing. Recent and ongoing activities aimed at improving bulk mechanical performance are also reviewed. These include approaches such as severe plastic deformation to refine grain structures and the development of new alloys. Where appropriate, data that demonstrates biocompatibility of these new niobium surfaces is also presented. Thus while niobium alloys have seen limited application to date, this chapter presents an overview showing the great potential for this material and the ongoing efforts in this regard.

Metallic materials have been used as biomedical implants for various parts of the human body for many decades. The physiological environment (body fluid) is considered to be extremely corrosive to metallic surfaces; and corrosion is one of the major problems to the widespread use of the metals in the human body since the corrosion products can cause infections, local pain, swelling, and loosening of the implants. Recently, the most common corrosion-resistant metallic biomaterials are made of stainless steels and titanium and its alloys along with cobalt–chromium–molybdenum alloys. It is well known that protective surface films of the alloys play a key role in corrosion of the metallic implants. Key documents on the corrosion behavior of the metallic biomaterials in human body have been compiled under this chapter as a review.

Metal allergy is thought to be caused by the release of ions from metallic materials. Extensive use of metal in jewelry, coins, surgical instruments, and dental restorations may be responsible for recent increases in allergy incidence. Metal allergic disease is categorized as a delayed-type hypersensitivity, which is developed more than 24 h after exposure to the causal metal. The hallmark of delayed-type hypersensitivity is the recruitment of lymphocytes and inflammatory cells, including T cells and granulocytes, to the site of allergic inflammation. During the development of metal allergy, T cells are known to play a role, and since metal ions are thought to function as haptens, T cell-mediated responses likely contribute to allergic disease. While the involvement of pathogenic T cells in the development of metal allergy has not been explored using animal models, studies utilizing human patient samples have been conducted. T cell clones, both CD4⁺ and CD8⁺, have been established from peripheral blood mononuclear cells of patients with metal allergy, and their responsiveness to the causal metal has been analyzed. It was found that metal ions induced proliferation of these T cells in vitro and some of the T cell clones produced IFN-γ or IL-4 after metal stimulation, while others produced both T helper 1- and 2-type cytokines. However, the subset of pathogenic T cells involved in the development of metal allergy and their cytokine profiles remain controversial. Recently, a novel animal model that reproduces human metal allergy has been established. Here we show the pathogenesis of metal allergy in the view of immunological responses using this animal model.

The increasing use of orthopedic and dental implants, such as joints and roots, has stimulated interest and concern regarding the chronic, long-term effects of metallic biomaterials used. This chapter focuses on cytotoxicity of metallic implants, particles, and ions. Metallic biomaterials may corrode and wear after being implanted in the body, which induces cytotoxicity and inflammatory. In addition, metallic particles and ions may be released through wear or abrasion. Therefore, it is important to understand the effects of metallic materials, including particles and ions, on surrounding cells and tissues. Reactions of fibroblasts and osteoblastic cells to metallic biomaterials have already been investigated by many researchers. Intensity of the cytotoxicity has been reported to depend on the kinds of metallic elements. Some metallic ions alter osteoblastic cell behavior and stimulate the cell functions, such as proliferation, differentiation, and mineralization, while for several ions, there is an appropriate amount for upregulation of such cell functions.