34
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bone bonding in vivo and is widely regarded as a positive indicator of bioactivity. Early studies on the 45S5 Bioglass® formulation determined that a permanent bone to bone tissue occurred in animal models2. This led to Bioglass® being commercially applied as an osteoconductive bone graft/void filler or both skeletal and dental applications. They are used currently for craniofacial defects including periodontal defects, alveolar ridge augmentation and dental extraction sites in bone tissue2, 3, 7-9.
The applicability of bioactive glasses and ceramics have increased since the success of 45S5 Bioglass®. Many glass-based medical materials such as glass-ceramic scaffolds for bone void repair3, 10-15, composites materials16, 17, glass microspheres18-20 and bone cements21-23 have been investigated. Glass has previously been applied for bone cementation to improve the bioactivity. Conventional bone cements are primarily based on acrylic polymers that are used for applications that include total hip and total knee arthroplasty (THA/TKA), in addition to spinal surgical procedures such as Vertebroplasty and Kyphoplasty23. Polymers such as polymetylmethacrylate (PMMA)23 and Bisphenyl-a glycidyal di-methacrylate (Bis-GMA)24 have appropriate mechanical properties for load bearing applications however, they lack any chemical interaction in vivo, and anchor implant materials through mechanical interaction with the surrounding bone tissue22, 23, 25. However, this lack of chemical integration will eventually lead to micro-motion within the joint space which can lead to the formation of fibrous tissue at the bone-bone cement interface. In addition, the curing of acrylic materials leads to high exothermic reactions which is known to damage the surrounding cell and soft tissues25. This has led to the inclusion of bioactive glass particles being incorporated into the materials to improve osseointegration with the host tissue. One commercially available composite material based on Bis-GMA chemistry included combeite (SiO2-Na2O-CaO) glass particles which resulted in the precipitation of a CaP surface layer when tested using Simulated Body Fluid (SBF) which greatly improved the bioactive response5, 26. Bioactive glasses are characterized by this ability which promotes osseous healing within the body. This process involves partial dissolution of the glass particulate surface which promotes ion exchange upon exposure to an aqueous physiological medium. The specific mechanism includes the release of soluble Si4+ into the surrounding medium in the form of silicic acid due to
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exchange with H+ and H3O. This mechanism results in the precipitation of an initial amorphous calcium phosphate layer which subsequently crystallizes to HaP3, 5, 27. Additionally, it is known that the ionic dissolution products from bioactive glasses can stimulate many critical physiological processes such as angiogenesis, and expression and upregulation several genes in osteoblasts28, which suggested that their applicability may influence many important processes in addition to mineral deposition in osseous tissue29. Therefore, the solubility of the glass particles is critical to promoting the desired bioactive response. An important characteristic that is critical to controlling glass solubility is related to the concentration of network formers/network modifiers within the glass30, 31. This will greatly influence the distribution of bridging oxygens (BO) and non-bridging oxygens (NBO) in the glass30, 32. It has previously been determined that the concentration of NBO (Si-NBO) has a significant effect on the glass solubility, and these NBO species are created by the inclusion of alkali/ alkali earth cations in the glass. This facilitates the ion exchange process and promotes the rate of Si4+ dissolution, and the bioactive response overall30, 31,
33.
The first part of this chapter aims to study the structure of glass compositions of SiO2-ZnO-CaO-SrO-P2O5-CuO used in novel glass-based adhesives, traditionally known as glass polyalkenoate cement (GPC). This composition was selected as it contains components that can serve a therapeutic value in vivo. Briefly, zinc has been cited to increase the rate of DNA synthesis in rat models34-36. Strontium is known to have a dual effect on the metabolism of bone cells where it increases the activity of osteoblast cells while at the same time decreasing the activity of osteoclast cells, which results in a net increase in bone mineral density37, 38. Silica, calcium and phosphate are primary components of the 45S5 Bioglass system and are critical determinants of the mineralization process. However, for this study the primary goal is to develop Cu containing glasses that can be used to form a skeletal adhesive. Cu has previously been cited as having promising bone metabolic properties in addition to being an antibacterial agent. The materials formed will be a novel class of glass polyalkenoate cements. GPCs are materials that were originally developed for use in restorative dentistry for lining, luting and filling applications. Traditional GPCs employ an aluminosilicate or fluoro-aluminosilicate based
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glass system as the aluminum (Al3+) plays a critical role in the setting of the materials39, however, neurotoxic concerns and claims of imparting defective mineralization has limited its use for GPC based bone adhesives40-42. When the glass component is mixed with Polyacrylic acid (PAA) and water, the surface of the glass partially degrades and releases cations that serve to crosslink the ionized PAA chains43. This results in a hard cement like material that can bond to both HaP in bone and tooth, in addition to bonding to surgical metals44. This acid-base setting reaction is non-exothermic and with the degradation of the glass, ionic species are liberated into the polysalt matrix43, 45-47. This study investigates the replacement of Si4+ with Cu2+ as Cu is cited as forming strong bonds with carboxylic acid groups on the PAA chains during setting48. This study investigates the effect that Cu has on the glass structure and solubility, characterizing important physical properties such as rheological and mechanical trends, in addition to determining the antibacterial effects49, 50 of Cu-GPCs in a range of relevant bacteria species. Bioactive Cu-GPCs could potentially be a safer and more practical alternative to antibiotic doped bone cements23, as the evolution of antibiotic resistant microbes such as methicillin resistant Staphylococcus aureus (MRSA) and vancomycin resistant Staphylococcus aureus (VRSA) are a persistent cause for concern when developing implantable bone cements.
3.3 Materials & Methods