Chapter 1
Bioceramics

María Vallet-Regí

Departamento de Química Inorgánica y Bioinorgánica, Facultad de Farmacia, Universidad Complutense de Madrid, CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Spain

1.1 Introduction

Ceramic materials are important sources of biomaterials for applications in biomedical engineering. Those ceramics intended to be in contact with living tissues are called bioceramics, and have experienced great development in the last 50 years. The medical needs of an increasingly aging population have driven a great deal of research work looking for new materials for the manufacture of implants. These are used to regenerate and repair living tissues damaged by disease or trauma. For specific clinical applications, mainly in orthopedics and dentistry, bioceramics are playing a key role.

In general, ceramics are inorganic materials with a combination of ionic and covalent bonding. The use of new ceramic materials represents an evolution of many aspects of mankind history. Many millennia ago, the possibility to store grains in ceramic receptacles allowed man to become a settler instead of a nomad hunter. Some centuries ago, the use of structural ceramics also brought great advances in the quality of life of man with the possibility of making clay bricks and tiles. Decades ago, ceramics produced a new revolution in the human way of life, with the development of functional ceramics in dielectrics, semiconductors, magnets, piezoelectrics, high temperature superconductors, and so on. In addition, ceramics have played an important role in improving the quality and length of human life through their use in biomaterials and medical devices.

As observed, the investigation of bioceramics has also evolved when, as will be explained later, more restrictive properties for the new ceramics were required. Thus, alumina, zirconia, calcium phosphates, and certain glasses and glass-ceramics are genuine examples of bioceramics. Figure 1.1 shows a classification of bioceramics according to their reactivity and their main clinical applications. Carbon is an element, not a compound, and conducts electricity in its graphite form, but it is considered a ceramic because of its many ceramic-like properties. Nowadays, new advanced bioceramics are under study, including ordered mesoporous silica materials or specific compositions of organic–inorganic hybrids.

Figure 1.1 Classification of bioceramics according to their reactivity. Particle size, crystallinity, and porosity are important factors to classify certain bioceramics, like apatites, in one group or the other. HA: hydroxyapatite, HCA: hydroxycarbonate apatite, A-W: apatite–wollastonite, TCP: tricalcium phosphate, OCP: octacalcium phosphate, DCPA: dicalcium phosphate anhydrous, DCPD: dicalcium phosphate dihydrate, TetCP: tetracalcium phosphate monoxide (See insert for color representation of the figure)

Ceramic materials have high melting temperatures, low conduction of electricity and heat and relatively high hardness. With regards to their mechanical behavior, ceramic materials exhibit great compression strengths and very much lower tensile strengths. Moreover, they are stiff materials, with high Young's modulus, and brittle because failure takes place without plastic deformation.

In relation to their surface properties, ceramics show high wetting degrees and surface tensions which favor the adhesion of proteins, cells, and other biological moieties. Furthermore, a ceramic surface can be treated to reach very high polish limits. Currently, as will be explained latter, much research effort is devoted to ceramics with interconnected porosity and in these cases the mechanical properties will change drastically.

Nowadays, it is possible to manufacture implants to replace any part of our body, except the brain.

Obviously, different types of materials are in use depending on the tissue to be replaced. Regarding the materials to be used, it is critical to bear in mind that a group of biomaterials will be applied in body reconstruction functions, hence they must perform their duty for an undefined period of time, that is, for the rest of the patient's life. Another group of biomaterials will be used in temporary body support functions. This “permanent” or “temporary” feature allows for a larger and better choice of materials for implant manufacture.

1.2 Reactivity of the Bioceramics

Many different factors affect the reactivity of any chemical substance and greatly determine its reaction kinetics. Figure 1.2 shows some of these. If we take into account the almost inert or bioactive nature of the different ceramics for medical applications, as well as kinetic factors such as particle size and porosity, three groups of bioceramics in use nowadays may be distinguished, inert, bioactive, and biodegradable, as we can see in Figure 1.1. The final purpose of the artificial synthesis of ceramics for bone replacement (hard tissue) is to implant a ceramic material able to regenerate the damaged bone. This is feasible if the ceramic is bioactive. Otherwise, if the ceramic is inert, the bone will be replaced by a material that the organism can tolerate, but which cannot substitute it by means of bone regeneration.

Figure 1.2 Governing factors in chemical reactivity of bioceramics. Composition in between glasses (disordered) and crystals (ordered) (See insert for color representation of the figure)

Reactivity, rather than the type of bioceramic is a suitable criterion to classify bioceramics. For instance, in the field of amorphous ceramics it is possible to obtain glasses that, in the same chemical system, behave as bioinert, bioactive, or resorbable because they have somewhat different compositions. It is also possible to find glasses with identical composition behaving as bioinert when obtained by melting, or bioactive when synthesized by a sol–gel method. Moreover, some glass compositions considered bioactive can be completely resorbed when used as particulates under a certain size limit, for instance, 90 µm for Bioglass® 45S5 (all this will be dealt with in Chapter 4). Analogous examples can be found among crystalline ceramics. For instance, the in vivo reactivity of hydroxyapatite (HA) can range from almost bioinert, when highly sintered as dense monoliths, to resorbable, when used in particle size, omitting the bioactive character generally attributed to HA (to be discussed in Chapter 3).

When some glass compositions presenting the highest levels of bioactivity were investigated, it was found that they were able to bond to hard and soft tissues, whereas other bioactive materials only bond to hard tissues. To explain these differences in reactivity Hench defined in 1994 two classes of bioactivity: class A, osteoproductive and class B, osteoconductive. The first occurs when the material elicits extracellular and intracellular responses whereas in the second only an extracellular response is obtained. It was explained that the ions released from these bioactive glasses, in particulate form, stimulated a regeneration of living tissues mediated by genes. These osteoproductive glasses were considered as third generation bioceramics and are the basis of the research efforts looking for new biomaterials that stimulate the cellular response. Nowadays the research efforts are concentrated on porous second generation bioceramics and new advanced bioceramics. In these materials the ceramic plays the role of a scaffold of cells and substances with biological activity (growth factors, hormones…) which are released to the medium in a controlled way. Thus, they are starting to be used in applications related to tissue engineering.

On the other hand, bioceramics must be biocompatible and functional for the required implantation time. They must also not be toxic, carcinogenic, allergic, or inflammatory. In general, because of their ionic bonds and chemical stability ceramic materials are biocompatible.

1.3 First, Second, and Third Generations of Bioceramics

The study of bioceramics can be divided into first, second, and third generations. The study of first generation bioceramics started in the 1960s, when the goal was reactivity as low as possible. The more representative examples of this kind of bioceramics are alumina, Al2O3 and zirconia, ZrO2. They are widely used as biomaterials because of their high strength, excellent corrosion and wear resistances, stability, non-toxicity, and in vivo biocompatibility. Around the 1980s the objective changed to obtain favorable interactions with the living body, namely a bioactive response or degradation. Specific compositions of calcium phosphates or sulfates, bioactive glasses, and glass-ceramics are examples of second generation bioceramics used clinically for bone tissue augmentation, as bone cements, or for metallic implants coating. As was indicated, in the last decade bioceramics with more demanding properties were required. The studies in third generation bioceramics are more based in biology and follow the purpose of substituting “replacement” tissues by “regenerating” tissues. This category includes bioceramics based on porous second generation bioceramics, loaded with biologically active substances, and new advanced bioceramics like silica mesoporous materials, mesoporous ordered glasses, or organic–inorganic...