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Bioactive Glasses
Fundamentals, Technology and Applications
By Aldo R. Boccaccini, Delia S. Brauer, Leena Hupa The Royal Society of Chemistry
Copyright © 2017 The Royal Society of Chemistry
All rights reserved.
ISBN: 978-1-78262-976-4
CHAPTER 1
Melt-derived Bioactive Silicate Glasses
SUSANNE FAGERLUND AND LEENA HUPA
1.1 Introduction
1.1.1 Glass – A Versatile Biomaterial
This chapter introduces some fundamental chemical and physical properties of glasses to be taken into account when designing and fabricating products based on bioactive glasses to be implanted inside the human body. The main emphasis is to explain the constraints to be taken into account from the materials science and chemical engineering points of view. The ultimate goal is to deliver the basic principles of glass science to serve as a platform for the various disciplines ranging from materials science to molecular biology, biochemistry, medicine, etc. The vision is that the steadily increasing multi-disciplinary experience provides the crucial knowledge needed for developing implants and scaffolds for controlled predetermined performance in the target application.
At first sight, the inherent brittle nature of glass does not make it a feasible material for implantable medical devices. At the same time, glass has several useful properties which support its utilization as a biomaterial. What is a biomaterial? Most biomaterials based on glasses or ceramics are designed to improve human health and the quality of life by restoring the function of living tissue and organs in the body. The single most important factor for a biomaterial is that it is able to be in contact with tissues of the human body without causing an unacceptable degree of harm to that body, i.e. the material is biocompatible. Recently, considerable research efforts have been directed to tailor highly porous tissue engineering scaffolds not only for bone tissue but also for emerging soft tissue applications. Detailed understanding of the nature and properties of glass provides a thorough basis for assessing its potential in prospective biomedical applications. In general, choice of a material for a particular application is based on its performance, properties, fabricability, and manufacturing costs.
1.1.2 Glass and Properties
Due to its amorphous structure glass possesses several features which make it an optimal material for manifold applications. Simplified, conventional inorganic glasses are homogeneous mixtures of oxides of alkalis, alkaline earths, aluminium, boron, silicon, etc. Most modern uses of these so-called soda lime glasses, including flat glass, hollowware glass and fibre glass, rely on the transparency to visible light combined with some other property, such as good mechanical strength, adequate chemical durability or electrical resistivity. Essentially, these commercial glass types are fabricated via the inexpensive melting route. They are easy to shape into various product forms at high temperatures when present as viscous liquids. In addition to the conventional glasses, specialty glasses possessing certain functional properties are essential in the modern everyday environment.
The functionality of the speciality glasses is often connected with the optical properties. Bioactive glasses used in contact with the living body as implants or as tissue engineering scaffolds belong to the family of speciality glasses. In contrast to most other applications, the transparency is not an essential property for the current applications of bioactive glass. Bioactivity of glasses may be defined in different ways, but common to all of these definitions is the requirement that the surface composition and morphology of the glasses change upon implantation. Simultaneously, the concentrations of the inorganic ions in the surrounding extracellular fluid change. Only glasses within certain limited composition range fulfil the requirements of bioactivity, i.e. show the desired interaction with the living tissue. Interestingly, whether it be transparency or the controlled surface reaction, the origin of the functionality of the glass is the same — the amorphous glass structure. As explained in Chapter 6 the amorphous glass structure enables adjusting the physical and chemical properties of glasses within certain limits merely by changing the constituent oxides or their ratios. This gives interesting possibilities to tailor the glass composition for various clinical applications.
1.1.3 Bioactivity of Glass
Bioactive glasses consist of the same oxides as conventional soda lime glasses but in proportions which give rise to large differences between several properties of these types of glass. The most marked difference dictating the bioactivity is the chemical durability; the bioactive glasses dissolve in aqueous environments at markedly higher rates than the soda lime glasses used, for example, in containers or windows. For the glass to be bioactive the dissolution rate must be compatible with the cellular processes so that the dissolving glass supports and enhances tissue regeneration and growth, while we expect the traditional glasses to be inert in their normal applications. Bioactive glasses thus provide temporary support to tissue healing and regeneration. Brittleness is one of the biggest challenges for utilization of bioactive glasses, especially in load-bearing applications. In future the problems with the brittleness may be solved by using the bioactive glass in composites together with polymers, or developing tissue engineering scaffolds with special architectures adapted to the requirements of loaded bone.
The first bioactive glasses studied as prosthetic materials were melt-derived compositions within the system Na2O-CaO-P2O5-SiO2. Glass was an interesting and smart choice for a material to be in contact with the human skeleton. The pioneering idea by Professor Hench, the inventor of bioactive glasses, was to develop a material that consists of elements abundant in the human body. In addition, the ratio between the oxides in the compositions studied was selected to favour rapid initial dissolution of alkalis from the glass surface in aqueous solutions followed by precipitation of an outer layer rich in calcium and phosphorus at the inner alkali-depleted silica layer. Virtually all glasses gradually dissolve in aqueous solutions, but the ion leaching rates and the tendency to form surface layers varies markedly depending on the total composition. It was hypothesized that if the composition of the calcium phosphate surface layer is similar to the hydrated calcium phosphate component in bone tissue, hydroxyapatite (HCA), the glass would not be rejected by the body. The compositions developing a HCA layer in vivo are today known as bioactive glasses.
Accordingly, the bioactive glasses were proven as advantageous materials in skeletal repair. Today, extensive research efforts are made to develop new compositions of bioactive glasses for bone and soft tissue engineering. Increasing knowledge of the influence of various ions released from the glasses on the tissue regenerative capability has inspired researchers to adjust and tailor bioactive glass compositions far beyond the original bone tissue related applications toward emerging areas in soft tissue regeneration. Though the history of bioactive glasses is longer than forty years, most commercial products today are used for treatment of trauma, disease or injury of bone tissue.
1.2 Properties Essential for Fabrication
1.2.1 Definition of Glass
For any utilization of a material we must understand its features and properties. All glasses, whether manufactured via melt quenching, sol–gel processing or some other suitable method, possess two common characteristics: the glass structure and the gradual change of several properties when heated or cooled between the solid form, glass, and the liquid form, melt. Glass is often defined as "an amorphous solid completely lacking long range, periodic arrangement of the atomic structure, and exhibiting a region of glass transformation behaviour". In this transformation the properties of the liquid gradually change into solid state properties. Some general rules of glass formation and the high temperature properties to be considered in glass forming processes are explained below. A detailed discussion of glass structure and its influence on glass properties is given in Chapter 3.
1.2.2 Glass Transformation and Liquidus Temperatures
Melt capable of forming a glass maintains its liquid-like structure as a super-cooled liquid below the melting point of the crystal, to transform into a brittle, elastic glass on further cooling. The transformation behaviour of a glass forming melt is depictured in Figure 1.1. The figure gives changes in the volume or the enthalpy at characteristic temperatures when the melt converts into either a crystalline state or forms a supercooled melt which transforms into a non-crystalline solid, a glass, on continued cooling. Glass transformation takes place at a certain temperature called the glass transition temperature or glass transformation temperature Tg This temperature depends on the composition of the glass but also on the cooling rate; the higher the rate the higher the transformation temperature. Glass transformation is thus a time-dependent behaviour and the value of Tg is always dependent on the thermal history of the glass.
Glass transformation temperature is measured normally from graphs recorded in thermal analysis or dilatometry of glasses, i.e. in heating glasses from the solid state into the molten state. The Tg value obtained depends on the heating rate, the instrumental method used in the measurement, and the thermal history of the glass. Below Tg the glass behaves as an elastic solid, around T.sub.g the glass shows viscoelastic behaviour, and above Tg the glass softens and starts to behave as a viscous liquid. The glass transformation temperature is thus an important parameter for selecting the experimental conditions in thermal treatment of a particular composition into various products above Tg. In addition, the annealing curve, i.e. controlled time-temperature history for relaxing any stresses present in the glass after the forming operations, is based on the Tg value. For bioactive glasses, the Tg value is of interest when sintering porous implants from powdered fractions or when estimating a suitable annealing curve for a monolith. However, Tg has no practical significance, e.g. in the quenching of glass melts into water to give glass particles. In contrast, if internal stresses in the particles caused by the quenching are to be relaxed, then an additional annealing step at around Tg is required.
If the melt were to crystallize during the cooling, abrupt change in the properties takes place when the crystal, with long range, periodic arrangements of the atoms, forms at the melting point (Tm in Figure 1.1), independently of the cooling rate. Since glass forming liquids have typically high viscosity at the melting point they easily form a supercooled liquid on cooling. For glass forming liquids, the melting point is often referred to as the liquidus temperature Tliq. The liquidus temperature is the highest temperature at which crystals can be in thermodynamic equilibrium with the melt. Thus, the value of Tliq (or Tm) does not depend on the melting history of the glass. From the manufacturing point of view, there is always a risk of crystallization if the melt is processed below Tliq In commercial soda lime-silica melts, crystals form within a few hours if held below the liquidus temperature.
The liquidus temperature is traditionally measured from glass samples treated in a furnace with controlled temperature profile for periods long enough to precipitate crystals which can be identified optically in quenched samples. The high tendency of bioactive glasses to crystallize in thermal treatments combined with the slow melting or dissolution of the crystals eventually formed during the heating questions the accurate determination of liquidus temperature in bioactive glasses. Thermal analysis is frequently used to estimate the temperature range in which the crystals melt.
1.2.3 Crystallization
A defect-free amorphous glass contains no crystals. Nevertheless, all glasses crystallize but at different rates in the temperature window between glass transition Tg and liquidus Tliq. Detailed understanding of crystallization is vital in fabrication processes requiring any longer thermal treatment in this critical temperature window. Although bioactive silicate glasses and soda lime-silica glasses are composed to a large extent from the same oxides, the markedly lower content of the main glass network forming oxide, SiO2, in bioactive silicate glasses gives easy crystallization.
Crystallization of a liquid happens via two processes: nucleation and crystal growth. In nucleation, a sufficient quantity of atoms form an ordered first structure (the nucleus) after which crystal growth is facilitated by new layers of atoms forming around the nucleus. For crystalline solids, these processes take place at the melting point, while for typical glass forming melts both nucleation and crystal growth show maximum values within certain temperature ranges below the melting point (Figure 1.2). All melt-derived glasses pass this critical crystallization range during the fabrication. The overlapping of the rate curves depends on glass composition and partly controls the suitability of a particular composition to thermal treatments in the temperature range from glass transition to melting point.
1.2.4 Crystallization of Bioactive Glasses 45S5, S53P4 and 13-93
Detailed information on crystallization mechanism, i.e. nucleation and crystal growth parameters, is available only for a few melt-derived bioactive glass compositions. In this chapter, the results from measurements of the characteristic values for bioactive glasses 45S5, S53P4 and 13-93 are discussed. Table 1.1 gives the oxide compositions of these three glasses. The original bioactive glass 45S5 Bioglass® developed by Professor Hench et al. and S53P4 BonAlive® developed by Andersson et al. are commercially available for certain clinical applications. The clinical applications of bioactive glasses are discussed in Chapters 14 and 19. Glass 13-93 was originally developed by Brink et al. to enable easier fabrication into shapes that are challenging from the glass manufacturing point of view. Since then, glass 13-93 has been used to manufacture continuous fibres and porous sintered implants or scaffolds by several research groups.
Crystallization of S53P4 and 13-93 takes place via surface nucleation and crystal growth mechanisms while for 45S5 the crystallization is more complex. For 45S5, smaller and larger particles are reported to show different nucleation mechanisms, and the crystallization proceeds rapidly from surface to the bulk. Phase separation above Tg into immiscible liquids precedes the nucleation in 45S5.
The crystallization mechanism is most often based on activation energy values, Johnson-Mehl-Avrami values, and nucleation-like curves determined from thermal spectra which are measured using certain temperature-time treatment in thermal analysis. The maximum nucleation rate for the primary crystals which form above Tg was around 560-580 °C for 45S5, while a slightly higher temperature of around 610 °C was suggested for S53P4. Correspondingly, the highest nucleation rate took place at 700 °C for 13-93. Crystal growth rate is markedly lower in 13-93 than in the two other compositions. In thermal treatment of 45S5 and S53P4 more than one crystalline phase may form depending on the temperature. Since this chapter focuses on properties and characterization of bioactive glasses, the crystallization is given only as a limiting factor for the fabrication window, while the phase separation and formation on secondary crystals are not considered.
The overall crystallization procedure is usually determined using differential thermal analysis or differential scanning calorimetry. A certain size fraction of glass particles is heated using a controlled rate (5–20 °C [min.sup.-1]) and thermal effects compared to an inert reference material are recorded as a function of temperature. Figure 1.3 shows typical thermal spectra for the three bioactive glasses 45S5, S53P4 and 13–93. The endothermic peak in the thermal spectra at around 500–600 °C gives the glass transformation while the exothermic peaks at around 600-800 °C (45S5 and S53P4) and 800–1000 °C (13–93) give the temperature spans at which crystals form upon heating.
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Excerpted from Bioactive Glasses by Aldo R. Boccaccini, Delia S. Brauer, Leena Hupa. Copyright © 2017 The Royal Society of Chemistry. Excerpted by permission of The Royal Society of Chemistry.
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