Thesis (Ph.D.)--University of Nebraska-Lincoln, 2008. / Title from title screen (site viewed Mar. 5, 2009). PDF text: x, 145 p. : ill. (some col.) ; 4.11 Mb. UMI publication number: AAT 3304243. Includes bibliographical references. Also available in microfilm and microfiche formats.

Hydroxyapatite (HA) is a biologically active ceramic that is used in surgery to replace bone. While HA promotes bone growth along its surface, its mechanical properties are not sufficient for major load-bearing medical devices. Carbon nanotubes (CNTs), as one of the strongest and stiffest materials available, have the potential to strengthen and toughen HA, thus expanding the range of clinical uses for the material. Furthermore, studies have suggested that the nanotubes themselves possess some bioactive properties. This work sought to develop and characterise HA-CNT composites in four main areas: 1) production and characterisation of green materials, 2) investigation of appropriate sintering atmospheres, 3) evaluation of mechanical properties, and 4) assessment of biological response to in vitro cell culture. HA was synthesised by a precipitation reaction between Ca(OH)2 and H3PO4, and multi-walled CNTs were produced by chemical vapour deposition. Composites were produced by adding the CNTs to the Ca(OH)2 solution as the HA was precipitating. Both as-made (nfCNTs) and acid-treated CNTs (fCNTs) were used to make composites with loadings of 0.5-5 wt.% CNTs. The resulting slurry was shear mixed and then processed to make a powder. The powder was then uniaxially pressed into tablets of ~45% theoretical density. Characterisation of the green material with XRD and FTIR found that the primary phase was HA which was well hydroxylated. The powder particles were found to have a bimodal size distribution, and all materials had similar surface areas, as determined by BET. Composites made with fCNTs were found to have a better dispersion of CNTs in the HA matrix and better interaction between the HA and CNTs compared with nfCNT composites. CNTs oxidise at the high temperatures needed to sinter HA, yet water is necessary to prevent dehydroxylation and decomposition of the HA. Using 5 wt.% fCNT composite, fourteen sintering atmospheres were investigated to determine their effect on phase purity, hydroxylation, sintered density, and remaining CNT content after sintering. An atmosphere of CO + H2 bubbled through ice water resulted in optimal properties. Additionally, it was found that increasing the gas flow rate and the number of samples sintered in one batch increased CNT retention. However, this came at the expense of the density of the sintered samples, as composites with a higher CNT content were more porous. To optimise the composite microstructure for mechanical studies, six different sintering time/temperature profiles were examined to determine their effect on density (balanced with CNT retention) and grain size. HA and both nfCNT and fCNT composites with CNT loadings of 0.5, 1, 2 and 5 wt.% were produced using the optimised atmosphere and profile, and then tested to determine tensile strength (using diametral compression) and hardness, and to look for evidence of toughening. It was found that CNTs had little reinforcing effect; instead, mechanical behaviour results were mainly attributed to differences in porosity, due at least in part to the CNTs' presence. The in vitro cellular response to the materials was examined by culturing human osteoblast-like cells on HA and nfCNT (0.88 wt.%) and fCNT (3.3 wt.%) composites for 12 days. Cells were found to attach and grow well on HA and the nfCNT composite, with slightly enhanced response on the composite. The fCNT composite, on the other hand, showed a decrease in cell viability between days 1 and 12. These results were mainly attributed to the effects of a lower local pH due to remnant acid on the fCNTs and differences in material characteristics, such as CNT loading and surface roughness. This systematic study of the production and properties of HA-CNT composites has resulted in improved understanding of the production and processing of these materials and the effects of a wide range of sintering atmospheres on their characteristics. Additionally, it has yielded interesting preliminary results of their mechanical reinforcement potential and biological behaviour.

The research activity described in the present thesis is devoted to the design and development of porous bioactive ceramic scaffolds addressed to the regeneration of bone tissue and was mainly carried out at the Institute of Science and Technology for Ceramics, belonging to the National Research Council of Italy (ISTEC-CNR), during my Ph.D. in Civil, Environmental and Mechanical Engineering (Curriculum B: Mechanics, Materials, Chemistry and Energy). The regeneration of critical size bone defects is still an unmet clinical need and since decades the development of bioactive scaffolds, capable to instruct and guide bone cells to tissue regeneration is a major research area in material science, including interdisciplinary approaches spanning from the field of chemistry, engineering, biology and medicine. In fact, the currently used bio-inert devices (e.g. metallic devices) can merely provide a mechanical support without regenerating the damaged bone tissue and often inducing adverse side effects such as infections while forcing the patient to frequent revision surgeries, with relevant socio-economic impact. The main aim of my work was the design and optimization of new materials and processes to produce bioactive ceramics implants as potential solution for the treatment of large and load-bearing bone defects, particularly suitable for cranio-maxillofacial, orthopaedic and spinal surgery. In my activity I synthesized new hydroxyapatite-based materials, Ca10(PO4)6(OH)2, exhibiting ionic substitutions designed to mimic the inorganic part of bone, particularly magnesium, strontium, zinc and carbonate, which increase the osteogenic ability and the bio-resorbability, promote the physiological bone turnover, thus suitable also for osteoporotic patients, as well as the antibacterial ability. After a general introduction of bone tissue physiology and an overview on the analytical methods involved in the research (Chapter I and Chapter II, respectively), my thesis focuses on the development of various hydroxyapatite nanophases showing multiple ionic substitutions including strontium or zinc ions, in association with magnesium and carbonate, with the purpose to provide synergistic biological effects such as osteogenic and antibacterial ability, and induce microstructural changes potentially improving the mechanical performance (Chapter III). In this Chapter, an important role was played by sintering, that was investigated varying different parameters like temperature and atmosphere (Air, CO2). The influence of doping ions and conditions of sintering was evaluated by chemical-physical, biological and mechanical characterization in order to understand how the presence of doping ions and different conditions of sintering influence the osteogenic properties and the mechanical behavior of the hydroxyapatite scaffolds. Then, Chapter IV describes novel nanocrystalline, multi-doped hydroxyapatite phases with excellent osteoinductive character and anti-infective properties, evaluated in collaboration with University of Pavia. Physico-chemical analysis highlighted the role of the surface state and charge, as induced by the ion doping, in the enhancement of the biological features. Finally, Chapter V describes the preparation of 3-D devices endowed where the porosity could be controlled and tailored to achieve suitable compromise between mechanical properties and porosity extent, relevant for bone invasion and osteointegration. The devices are obtained via direct foaming of multi-doped hydroxyapatite ceramic suspension with high-energy planetary ball milling. This method enabled the development of large and complex shape porous scaffolds, recapitulating composition, porosity and structure of the natural bone, thus promising for future practical applications in bone surgery. A better understanding of how dopant ions affect the mechanical properties of these scaffolds has been made possible thanks to the several mechanical and microstructural tests performed on them.

Caries is one of the most common diseases in dentistry. The key to preventing caries is the balance between demineralization and remineralization. Dental delivery methods such as toothpaste, gels, and varnishes are commonly applied as preventative methods against caries. With the advancement of nano-technology, dentistry can supplement traditional diagnostic and treatment methods with more advanced, efficient, and personalized dental care. Hydroxyapatite (HA) is a biomimetic agent that aims to remineralize and protect the enamel from erosion. It is formed by nanoparticles similar to apatite crystals of tooth enamel. Furthermore, it is one of the most biocompatible and bioactive materials. Because HA is present in our enamel, it will be proven as an effective biomimetic agent for the prevention and remineralization of caries. The Caries Management by Risk Assessment (CAMBRA) tool helps dental care professionals identify high-risk patients more susceptible to caries. With the addition of biomimetic agents such as hydroxyapatite, dentists can effectively provide treatment to detect early-stage lesions and correctly intervene with remineralization techniques in all patient types. Studies have shown that HA toothpastes have anti-bacterial properties against S. mutans caries causing bacteria, and inhibit demineralization, similar to fluoride. In orthodontic patients, no significant difference was found between fluoride and HA dentifrice on caries progression nor between HA and fluoride gel in remineralizing initial caries. Similar reports found non-inferiority of hydroxyapatite toothpaste compared to fluoride toothpaste. Fluoride's mechanism of action differs from HA in that hydroxyapatite protects enamel by creating a new layer of enamel, and fluoride hardens the existing enamel layer. A comparison of three biomimetic agents, Casein Phosphopeptides Amorphous Calcium Phosphate (CPP-ACP), Tricalcium Phosphate (TCP), and hydroxyapatite found hydroxyapatite to have the highest amount of remineralization with nHA being more effective in managing early caries and decreasing lesion depth. Hydroxyapatite toothpaste was also shown to be a favorable alternative to oxidizing bleaching agents and zinc-carbonate hydroxyapatite being more effective than a fluoride/potassium nitrate dentifrice in reducing dentin hypersensitivity. With the high consumption of acidic food and beverages, a Zinc-nHA toothpaste was to be more effective than fluoride toothpaste in remineralization and protection after the acid attack and demineralization from Coca-Cola. In conclusion, with the reported results of the studies in this paper, it is known that nano- hydroxyapatite is an effective and safe alternative to fluoride. Many studies have proven nano-hydroxyapatite effective in helping to remineralize early carious lesions. In some studies, it is just as promising as fluoride is. It is especially beneficial for high-risk patients to implement nHA into their oral care routine. Nano-hydroxyapatite (nHA) has been proven to promote remineralization, inhibit demineralization, whiten teeth, protect against dental erosion, and reduce dentin hypersensitivity.

No description available.

Faculty of Health Sciences, Degree of Master of Science in Medicine. 9208366a / The initiation of new bone formation within the porous spaces of hydroxyapatite (HA) implants involves the expression of osteogenic markers belonging to the TGF-β superfamily. To study the genetic expression of these osteogenic markers in relation to the type of HA implant used and implantation period, five different types of porous HA biomaterials were implanted in the rectus abdominis muscles of adult baboons Papio ursinus, and were harvested at two, three and 12 months. The total RNA of all harvested samples was extracted and analysed using the Northern blot technique. The results showed that Collagen type IV, GDF-10 and BMP-7 were expressed at the early time points at relatively high levels, and their expression levels were significantly reduced at 12 months. The expression of these makers was not affected by the type of porous HA implant used. The histological sections of these specimens at two and three months showed vascularised connective tissue within the porous spaces of the implants with no bone formation. However, at 12 months there were substantial amounts of bone formed in all the studied implants. The down-regulation of the expressed osteogenic markers at 12 months correlates to the amount of bone formed, suggesting some negative feedback mechanism which may be acting via inhibitory Smads proteins in relation to the amount of bone formed. Neither TGF-β1 nor BMP-3 messages were detected in any of the studied samples, It is possible that these bone markers are not expressed locally within the vicinity of the porous HA implants but are adsorbed to the HA implants from the circulatory system.

The aim of this project was to study the in vitro release of cephalothin, vancomycin and strontium from hydroxyapatite particles and its PMMA composite. The hydroxyapatite spheres containing strontium were prepared in the laboratory. The in vitro release study for the hydroxyapatite was carried out in phosphate buffer saline solution (PBS) with differing pH value at 37 °C for five days and the PMMA composites for 21 days. All of the releases showed a burst release within the first 24 hours followed by a slow release. The pH value of the release medium had influence on the release rate to some extent for the antibiotic release and the acidic solution had a more significant impact on the strontium release. All of the composite groups had a much lower strontium release rate than the strontium release from the hydroxyapatite spheres.

published_or_final_version / abstract / toc / Orthopaedics and Traumatology / Doctoral / Doctor of Philosophy

Thesis (M. Phil.)--Hong Kong University of Science and Technology, 2004. / Includes bibliographical references. Also available in electronic version. Access restricted to campus users.

Thesis (Ph. D.)--University of Washington, 2000. / Vita. Includes bibliographical references (leaves 185-195).