The primary objective of this work is to reformulate glass composition used in the Al-free GPCs by incorporating Cu in the glass composition, and to investigate the effect of Cu on the rheology, mechanical properties and in vitro suitability of zinc based GICs. Glass composition modification based on Cu incorporation is performed for two main reasons:
1.) to improve physical properties and mechanical strength between cement and bone mineral, and 2.) to improve biological behavior and the antibacterial efficacy of the resultant GPCs. Divalent cations in the glass have the potential to link two polyanion chains. Where the ionic strength of the bond proceeds as M=Al3+>Cu2+>Zn2+>Ca2+>Mg2+
63, Cu2+ can act as a strong ionic crosslink to carboxylic acid (COO-) side groups, resulting in hardened set materials, which suggests the Cu is a mechanically relevant ion when formulating GPCs.
Cu has been widely cited as an antibacterial material in health care settings105. The study of the antibacterial properties of metallic Cu surfaces is a relatively recent development and has gained momentum. Prior to that, a number of studies have already dealt with the kinetics of contact killing upon exposure of bacteria to Cu surfaces. The disruption of microbes due to the presence of Cu ions appears to occur in three parallel
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ways (Figure 2.10) and as such, prevents the risk of bacterial resistance106. As it is depicted in Figure 2.10, there are four possible mechanisms for antibacterial effects of Cu; (a) Cu dissolves from the copper surface and causes cell damage, (b) The cell membrane ruptures because of Cu and other stress phenomena, leading to loss of membrane potential and cytoplasmic content, (c) Cu ions induce the generation of reactive oxygen species (ROS), which cause further cell damage, and (d) Genomic and plasmid DNA becomes degraded.
Contact with Cu surfaces has been shown to damage the integrity of bacterial membranes, Cu ions can directly damage bacterial proteins and they can also induce the formation of highly damaging hydroxyl radicals via a Fenton-like chemistry, which can then damage the cells via their interactions with DNA, enzymes and other proteins, as well as the peroxidation of lipids and subsequent membrane damage106-107.
Figure 2.10. Mechanisms of Cu antibacterial properties (a) Cu causes cell damage, (b) cell membrane rupture, (c) generation of ROS, and (d)
DNA degradation107.
Cu ions have been reported to be an essential component of the angiogenic response106, 108. Cu ions have been reported to stimulate the proliferation of endothelial cells in a dose dependent manner during in vitro culture, and the ability of Cu ions to promote wound healing in rats has been linked to the upregulation of VEGF expressed by stimulated cells which plays a very important role in cell differentiation and in blood vessel formation105, 109. Another important benefit of Cu ions is the low cost and the high stability
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when are compared with growth factors. Furthermore, these metallic ions are vital in human metabolism due to the significant amount found in human endothelial cells in the course of physiological angiogenesis110.
For the reasons mentioned above, Cu has been combined with biomaterials in order to improve the biological effect. Previous studies suggested that incorporation of Cu ions in bioactive materials is a feasible way to improve antibacterial properties and angiogenesis. In some recent studies, various concentrations, up to 10 mol% of copper oxide were used, in order to demonstrate the properties of this metal oxide in various glass systems111-113. Popescu et al. reported highly antibacterial, bioactive, and biocompatible glass ceramics by incorporation of 4 mol% CuO114. In another study, Lin et al showed that Cu-BGC scaffolds significantly facilitated the regeneration of cartilage and osteochondral interface, as well as inhibited inflammatory response, which may prevent the development of osteoarthritis associated with osteochondral defects113. Bernhardt et al directly mixed Cu2+ solutions with calcium phosphate cements and found that Cu2+ ions could enhance cell activity and proliferation of osteoblastic cells115. It was found that Cu has a positive influence on the angiogenic mechanisms of blood vessel formation, enhances bone metabolic activity, has a valuable antibacterial action, and could play the role of an enzymatic cofactor in metabolic signals during tissue formation116-117.
The research contained herein, covers four main tasks:
1. Development of novel Cu incorporated glasses for synthesizing GPCs, by incorporating of Cu in the base glass composition and furthermore characterizing glasses with respect to structural changes and glass solubility.
2. Synthesizing GPCs and investigating their rheological behavior, evaluating their mechanical properties and bond strength as outlined by relevant ISO standards.
3. Analyzing solubility and biocompatibility of GPCs with respect to their ion release profiles, antibacterial activity, mineralization potential through SBF trials and cytocompatibility with respect to maturation times in DI water.
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4. Investigating the surface crystallization of the of heat-treated glass particles, to modify the cross-linking mechanism in the setting reaction, and to improve the mechanical properties of the resultant GPCs.
Next chapter is focused on the structural characterization of the novel Cu- containing glass series and extrapolating their potential to form glass-based adhesives, traditionally known as glass polyalkenoate cement (GPC). The first part of the next chapter describes the chemistry and morphology of the glasses, and the structural effects of Cu incorporation in glass, using DTA, MAS-NMR, XPS. Later on, GPCs will be formulated, and some of the preliminary results regarding the rheological, compressive strength, and antibacterial properties of will be examined.