Kaj H. Karlsson

Calcium phosphate formation at the surface of bioactive glass in vivo

The calcium phosphate formation at the surface of bioactive glass was studied in vitro. Glass rods and grains were immersed in different aqueous solutions and studied by means of scanning electron microscopy and energy dispersive x-ray analysis. Surface morphological changes and weight loss of corroded grains were monitored. In-depth compositional profiles were determined for rods immersed in the different solutions. The solutions used were tris-buffer (tris-hydroxymethylaminomethane + HCl), tris-buffer prepared using citric acid (tris-hydroxymethylaminomethane + C6H8O7.H2O), and a simulated body fluid, SBF, containing inorganic ions close in concentration to those in human blood plasma. It was found that the calcium phosphate formation at the surface of bioactive glass in vitro proceeds in two stages. When immersing the glass in tris or in SBF a Ca,P-rich surface layer forms. This accumulation takes place within the silica structure. Later, apatite crystals forming spherulites appear on the surface. The Ca/P-ratio of initially formed calcium phosphate was found to be about unity. It is proposed that this is due to bonding of phosphate to a silica gel. The surface is stabilized, i.e., leaching is retarded, by the rapid Ca,P-accumulation within the silica structure before apatite crystals are observed on the surface. It is proposed that the initially formed calcium phosphate is initiated within the silica gel. The crystallizing surface provides nucleation sites for extensive apatite formation on the glass surface. In the presence of citrate no Ca,P-accumulation occur at the glass surface, but soluble Ca-citrate complexes form. By comparing the weight loss during corrosion in tris with that in the calcium and phosphate containing SBF, it is possible to establish whether the glass can induce apatite formation at its surface or not.

A structural approach to bone adhering of bioactive glasses

Abstract Some silicate glasses exhibit the property of bonding to bone. In vivo tests show that a layer of silica gel is always formed on the glass surface when the bonding is successful. From a comparison with the silicon chemistry of diatoms and connective tissues it is apparent that silicate chelates form an essential step in the formation and mineralization of hard tissues. The same kind of chelating is also demonstrated for silicate anions in binary melts. It is suggested that in implants, the silica gel formed on the glass surface not only acts as a chelating agent, but also is flexible enough to supply the correct atomic distances required by the crystal structure of bone apatite. The phosphate phase used in most bioactive glasses is suggested to act as a source for a phosphate buffer, which adjusts the surface acidity of the glass implant.

On the bioactivity of silicate glass

Abstract In order to improve the properties of bioactive glasses, one must be able to control the bioactivity. This requires a good description of the bone bonding mechanism or, preferably, a good understanding of it. In this paper the bioactivity is approached both phenomenologically and deterministically. The phenomenological description of the property-composition relationship provides a tool for the formulation of bioactive glass compositions. The complexation of phosphate by the initially formed silica gel is proposed as the mechanism responsible for the bioactivity.

Effect of immersion in SBF on porous bioactive bodies made by sintering bioactive glass microspheres

Abstract Since the mid 90s it has been possible to draw fibers and manufacture microspheres of novel bioactive glasses. Thus, by sintering bioactive glass microspheres it is now possible to form porous textures, in which the bioactive surface area is increased manifold compared with non-porous bodies. Four different types of porous bodies were made by sintering glass microspheres of diameter 250–300 μm. Two of the body types contained only one kind of spheres; either highly bioactive glass spheres or spheres made of glass having a low bioactivity (biocompatible glass). Two additional types of test bodies were obtained by sintering mixtures of bioactive and biocompatible spheres (composites). The dissolution of silica and calcium into simulated body fluid (SBF) was determined at different time intervals using a direct current plasma atomic emission spectrometer (DCPAES). The influence of immersion on the mechanical strength of the porous structures was studied by means of a compression test. Further, the thickness of the silica-rich gel formation on the surface of bioactive glass spheres was measured at each time interval using back-scattered electron imaging of scanning electron microscopy (BEI-SEM). A non-porous glass rod made from the same bioactive glass was used as the control. The results showed that dissolution of silica and calcium into SBF from the porous glass texture was inversely related to the silica content of the glass. The rate of silica gel formation on the sintered bioactive microspheres was significantly higher than on a rod made from the same glass. The initial mechanical strength of porous bodies consisting of only one kind of glass was 17–20 MPa. However, these bodies lost their mechanical strength at an early stage of the immersion showing compression strength of only 7–8 MPa at 14 days of immersion. The initial strength of composite glass bodies (7–11 MPa) was lower compared with bodies containing only one kind of glass but the bodies showed no notable mechanical weakening during the test. Softening of the surface of smooth bioactive glass plates correlated well with the formation of the silica-rich layer on the plate. Interestingly, the study also showed that in porous glass structures containing both bioactive and biocompatible glass the biocompatible glass can act as a site for calcium phosphate precipitation.

Porous bone implants

Porous conical implants made by sintering micro-spheres made from bioactive and bio-compatible glasses have been tested mechanically as well as in vivo by inserting the implant through the cortical bone into the bone marrow. The behaviour is compared to a reference implant made by sintering micro-spheres of metallic titanium. Due to capillary forces the implant pores were filled with bone marrow fluid when inserted. An extended bone ingrowth occurred in the cones of bioactive glass, in the titanium ones only in the cortical area. Further, the factors influencing the formation of a chemical bond between glass and living tissue are discussed.

Short-term Reaction Kinetics of Bioactive Glass in Simulated Body Fluid and in Subcutaneous Tissue

ABSTRACT Reaction kinetics of a bioactive glass (S53P4) were compared for up to 72 hours in simulated body fluid (SBF) and in subcutaneous tissue. The samples were studied by scanning electron microscopy and energy dispersive X-ray analysis. Glass tested subcutaneously or in SBF at SA/V of 0.4 cm−1 induced calcium phosphate formation more rapidly than glass tested in SBF at a SA/V of 0.1 cm−1. However, a pure apatite surface layer developed more rapidly at the low than at the high SA/V ratio or subcutaneously. The calcium phosphate accumulation started later but continued more rapidly at the low than at the high SA/V ratio. Attachment of fibers, most likely collagen, and their mineralisation at the glass surface indicates ability of the glass to bond to soft tissue.

Structural units in silicate glasses

Abstract When stoichiometric constraints are considered, incorporating three-, four- and six-rings of silica tetrahedra simultaneously into a structure restricts the number of alternatives to two sequences, a cristobalite-like for Na- and a tridymite-like for K- and Cs-silicates. It is suggested that only three- and six-rings are present in Li-silicate structures, which leads partly to clusters of less defined sizes and partly to mono- and disilicate ions. These sequences are supported by voltammetric measurements in melts and give a structural basis for the interpretation of Raman and NMR data of solid glasses.

Acidity and ionic structure of molten alkali silicates

An attempt has been made to identify the structural elements in binary lithium, sodium, potassium and cesium silicate melts by voltammetry. In the lithium melts g-SiO2 or quartz-like clusters are proposed, although other interpretations are possible. Further, a second voltammetric wave may be an indication of peroxo bonds in lithium melts. In sodium melts, anions derived from cristobalite have been confirmed by comparison with information from Raman spectra, as have the tridymite derivatives in potassium melts. The structural elements in cesium silicate melts resemble those of potassium. The influence of the alkali ion on the acidity of the melt is calculated and is found to increase in the order Cs < K < Na < Li.

On the structure of silicate melts

Abstract A striking similarity is obtained between the structure of binary silicate melts and the Qn distribution in the corresponding glasses. The former are deduced from voltammetric measurements, the latter from published Raman and NMR data. A closer analysis of Raman data based on the proposed neutralisation and depolymerisation scheme for anions in melts is therefore suggested.

Chapter 6:Tailoring of Bioactive Glasses

Development of new bioactive glass compositions to a particular application is often based on minor changes in the composition of a glass with well-established properties. The final glass composition should then hopefully meet all the criteria set by the biological behaviour of the bioactive glass device in the implantation site. The composition must also satisfy various criteria of fabrication. Thus, in composition tailoring, several important criteria must be fulfilled. This chapter discusses various principles and possibilities of tailoring bioactive glass compositions from materials research and chemical engineering points of view. The goal is to explain the possibilities offered by various property–composition relations to tailor and choose the best composition for a specific application. Tailoring can greatly reduce the number of in vitro and especially in vivo tests. Choice of glasses for emerging future applications in hard and soft tissue engineering requires a multidisciplinary understanding of both the properties of the glass during manufacture and the performance of the final bioactive glass device over the time needed for tissue regeneration or healing.