β – Tricalcium phosphate (β-TCP, Ca3(PO4)2) is a commonly used bone substitute material due to its biocompatibility and resorption. This study focused on the production of almost fully dense β-TCP ceramics with varying degrees of impurities (Ca/PO4 ratio, addition of 5% Mg). Three methods were used to produce the β-TCP ceramics, uniaxial pressing, slip-casting and isostatic pressing. In this study the isostatic pressing and sintering at 1150ºC for 20h and 15min, resulted in the densest β-TCP ceramics (97.7-99.2%). No significant differences of grain size and density could be detected between the samples produced with various compositions. These isostatically pressed samples sintered at 1150ºC were then dissolved in 0.08M aceticacid solution to simulate the in vivo resorption. It was found that the samples containing extra Mg dissolved slower. Attempts to determine the chemical composition of the grain boundaries were made without success. However, SEM observations of partly dissolved β-TCP ceramics revealed that the grain boundaries dissolved faster than the grains. The study was performed at the RMS foundation in Switzerland.

The silicon complexes in silicon doped calcium phosphate bioceramics have been studied using $^{29}$Si magic angle spinning nuclear magnetic resonance spectroscopy. The replacement of phosphorus by silicon in these materials requires a charge compensation mechanism which is difficult to study by many experimental techniques due to the small amount of silicon added. Producing these materials using an isotopically enriched source of silicon made the use of NMR spectroscopy feasible. Three different materials have been studied: a multiphase material commercially available under the trade name Skelite$^{\rm TM}$ composed of predominantly a silicon stabilized $\alpha$-tricalcium phosphate ($\alpha$-TCP) phase as well as a silicon doped hydroxyapatite (HA) phase, a single phase Si-HA material and a single phase silicon stabilized $\alpha$-TCP material. Slight changes to the material production method were first introduced to accommodate the switch to an isotopically enriched silicon source. Characterization of the enriched materials was carried out using Rietveld refinement of X-ray powder diffraction spectra and X-ray fluorescence spectroscopy to confirm that these materials were similar to the previously studied, non-enriched, materials in terms of the silicon contents, Ca/(P+Si) molar ratios and lattice parameters. NMR Spectroscopy showed that in all three materials, the silicon formed Q$^1$ structures in which two silicate tetrahedra joined together by sharing an oxygen, creating an oxygen vacancy which compensated the substitution of two silicon for phosphorus. This is the first observation of this charge compensation mechanism in Si-HA and may explain the interesting phase evolution previously found in the system studied in this work in which the Si-HA transforms to silicon stabilized $\alpha$-TCP upon sintering. / Thesis (Master, Physics, Engineering Physics and Astronomy) -- Queen's University, 2007-12-18 14:45:38.721

En raison de l’augmentation de l'espérance de vie, le nombre de personnes âgées et par conséquent le taux de maladies chroniques augmente de plus en plus nécessitant le développement de nouveaux biomatériaux permettant la réparation osseuse. Le but de cette étude était d'évaluer le comportement in vitro de cellules ostéoprogénitrices cultivées sur des pastilles de phosphate tricalcique dopées (β-TCMP, Mg/Ca = 0,15) ou non (β-TCP) avec du magnésium dans un environnement statique et dynamique (débit de 0,3 mL/min), ainsi que la réponse de macrophages humains après contact avec des extraits des matériaux (ISO10993-12). Les pastilles de β-TCMP et β-TCP ont été obtenues par frittage respectivement d’une apatite calcium déficiente en calcium dopée au magnésium et de TCP (Merck). Les diffractogrammes et les spectres infrarouge ont confirmé la production de β-TCP et de β-TCMP, ratio Mg/Ca = 0,14. Des cellules osteoprogénitrices STRO+1A ont été cultivées sur des pastilles pendant 21 jours et leur comportement de prolifération et de différenciation cellulaire ont été vérifiés. Aucune différence entre les deux pastilles n’a été observée concernant le nombre de cellules après 21 jours de culture, ni sous condition statique ni dynamique. Cependant, il semble que l'environnement dynamique accélère la différenciation ostéoblastique. D'une façon générale, le β-TCMP n'a pas modifié la réponse des macrophages (le profil des cytokines) activés ou non par du lipopolysaccharide bactérien, cultivés pendant 72 heures avec des extraits de biomatériaux, par rapport au β-TCP. D’après ces résultats, les deux biomatériaux semblent être prometteurs pour le traitement des pertes osseuses. / Research on bone tissue regeneration is constantly expanding due to the improvement of life expectancy with a consequent increase in the rate of chronic diseases. The aim of this work was to evaluate the in vitro behavior of STRO+1A osteoprogenitor cells cultured onto dense tablets of tricalcium phosphate doped (β-TCMP, Mg/Ca = 0.15) or not (β-TCP) with magnesium under static and dynamic (flow rate of 0.3 mL/min), as well as the response of human macrophages after contact with the granules extracts of the materials (ISO10993-12: 2007). The β-TCMP and β-TCP tablets were obtained by sintering a calcium-deficient apatite doped with magnesium and commercial TCP (Merck), respectively. The diffractograms and infrared spectra confirmed the presence of β-TCP and β-TCMP with a Mg/Ca ratio of 0.14 (plasma spectrometry). A cell density of 5x103 was inoculated onto the tablets and then STRO+1A were cultured at 37°C/5% CO2 for up to 21 days, in which the proliferation and differentiation rate were assessed. There was no difference in cell density between the materials after 21 days of culture, neither under static nor dynamic conditions; however, it seems that the dynamic environment accelerated osteoblast differentiation. In a general way, β-TCMP did not change the response of macrophages (cytokine profile), activated or not, by bacterial lipopolysaccharide, cultured for up to 72 hours with the extracts of biomaterials, when compared to β-TCP. Based on these results, both materials appear to be adequate for bone loss therapy.

Este trabalho teve como objetivo avaliar as propriedades biológicas de cimentos experimentais a base de resina metacrilato contendo α-tricálcio fosfato (α-TCP) ou hidroxiapatita nanoparticulada (HAp) in vitro e in vivo. Para isto, os cimentos experimentais foram avaliados e comparados com AH Plus (AHP). Na etapa in vitro, os materiais foram mantidos em contato com meio de cultura por 24 horas, coletados e avaliados na concentração de 10%. Células-tronco da papila apical humana (SCAPs) foram submetidas aos ensaios de viabilidade brometo de 3-(4,5-dimetiltiazólio)-2,5-difenil tetrazólio (MTT) e sulfurodamina B (SRB) no período de 24 horas; e a bioatividade foi avaliada pela atividade da enzima fosfatase alcalina (ALP) e deposição de nódulos mineralizados pelo corante vermelho de Alizarina (AR), nos períodos de 1, 5, 10 e 15 dias. Na etapa in vivo, os materiais foram inseridos em tubos de polietileno e colocados no tecido subcutâneo de ratos para avaliação da reação inflamatória, sendo utilizado um tubo vazio como controle e avaliados os períodos de 7, 30 e 90 dias; para avaliação da deposição óssea, os cimentos α-TCP e AHP foram inseridos em cavidades confeccionadas no fêmur de ratos, sendo utilizada uma cavidade vazia como controle e avaliados os períodos de 30 e 90 dias. Para o ensaio de viabilidade e ensaios in vivo, foram utilizados os testes de Kruskal-Wallis e post hoc de Dunn; para avaliação da bioatividade in vitro foram utilizados os testes ANOVA e post hoc de Tukey (P < 0.05). HAp e AHP não apresentaram diferenças estatísticas entre si em ambos os ensaios de citotoxicidade (P> 0,05) e o α-TCP apresentou menor resultado de viabilidade no teste MTT, sendo estatisticamente diferente dos outros (P <0,05). Os ensaios de bioatividade demonstraram aumento na atividade da ALP em todos os grupos (P < 0.05). Observou-se semelhança entre os grupos no primeiro período (P > 0.05), AHP apresentou menores valores em 5 dias (P < 0.05), α-TCP apresentou os maiores valores em 10 dias (P < 0.05), e em 15 dias este cimento foi superior ao AHP (P < 0.05). AR mostrou aumento na quantidade de depósitos mineralizados após 5 dias (P < 0.05). Não houve diferença entre os grupos em 1 dia (P > 0.05), α-TCP, HAp e controle foram semelhantes aos 5 dias (P > 0.05), e em 10 e 15 dias, α-TCP apresentou os maiores valores, sendo diferente dos outros cimentos (P > 0.05). Na avaliação da resposta inflamatória in vivo, observou-se diminuição da inflamação e aumento de fibras colágenas em todos os grupos. Em 7 dias, α-TCP e HAp mostraram resultados semelhantes ao controle CT (P>0.05) e diferentes do AHP (P < 0.05), que foi o único grupo a apresentar células-gigantes neste período. Na avaliação da deposição óssea, houve aumento na deposição de 30 para 90 dias nos grupos α-TCP e controle (P < 0.05), e estes grupos apresentaram resultados semelhantes em 90 dias (P > 0.05), diferindo do AHP (P < 0.05). Conclui-se que a associação de fosfatos de cálcio à resina metacrilato apresentou bons resultados de biocompatibilidade e bioatividade in vitro e in vivo, apresentando potencial para serem utilizados como cimentos obturadores na prática clínica. / This study aimed to evaluate the biological properties of experimental sealers containing α-tricalcium phosphate (α-TCP) or nanoparticulate hydroxyapatite (HAp) in a methacrylate resin-base in vitro and in vivo. For this, the experimental sealers were evaluated and compared with AH Plus (AHP). At the in vitro assays, the materials were kept in contact with culture medium for 24 hours, collected and evaluated at concentrations of 100% and 10%. Stem cells from human apical papilla (SCAPs) were submitted to 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and sulfurodamine B (SRB) viability assays for 24 hour; and bioactivity was evaluated by alkaline phosphatase enzyme activity (ALP) and deposition of mineralized nodules by Alizarin Red staining (AR), for 1, 5, 10 and 15 days. At in vivo assays, the materials were inserted in polyethylene tubes and placed in subcutaneous tissue of rats to evaluate the inflammatory reaction, using an empty tube as control and evaluating the periods of 7, 30 and 90 days; to evaluate bone deposition, α-TCP and AHP cements were inserted into cavities made in the femur of rats, using an empty cavity as control and evaluating the periods of 30 and 90 days. For viability and in vivo assays, Kruskal-Wallis and Dunn’s post hoc tests were used; for bioactivity, ANOVA and Tukey's post hoc tests were used (P < 0.05). HAp and AHP did not presented statistical differences from each other in both citotoxicity assays (P > 0.05), and α-TCP presented a lower viability result in MTT assay, being statistically different from the other sealers (P < 0.05). The bioactivity assays showed an increase in ALP activity for all groups (P < 0.05). Similar results were found between the groups at the first period (P > 0.05), AHP had the lowest values at 5 days (P < 0.05), α-TCP presented the highest values at 10 days (P < 0.05), and at 15 days, this sealer’s values were higher than AHP (P < 0.05). AR showed an increase in the amount of mineralized deposits after 5 days for all sealers (P < 0.05). No difference between groups were found at 1 day (P > 0.05), α-TCP, HAp and control were similar at 5 days (P > 0.05), and at 10 and 15 days, α-TCP presented the highest values, being different of the other sealers (P > 0.05). Regarding the evaluation of the inflammatory response in vivo, there was a decrease in inflammation and increase of collagen fibers in all groups. At 7 days, α-TCP and HAp showed similar results to the control (P > 0.05) and different from AHP (P < 0.05), which was the only group to present giant cells in this period. In the evaluation of bone deposition, there was an increase in deposition from 30 to 90 days for α-TCP and control groups (P < 0.05), and these groups presented similar results in 90 days (P > 0.05), differing from the AHP (P < 0.05). It was concluded that the association of calcium phosphates and methacrylate resin showed good biocompatibility and bioactivity results in vitro and in vivo, presenting potential to be used as endodontic sealers in clinical practice.

Understanding, and ultimately, predicting the degradation of bioresorbable composites made of biodegradable polyesters and calcium-based ceramics is paramount in order to fully unlock the potential of these materials, which are heavily used in orthopaedic applications and also being considered for stents. A modelling framework which characterises the degradation of bioresorbable composites was generated by generalising a computational model previously reported in literature. The framework uses mathematical expressions to represent the interwoven phenomena present during degradation. Three ceramic-specific models were then created by particularising the framework for three common calcium-based fillers, namely tricalcium phosphate (TCP), hydroxyapatite (HA) and calcium carbonate (CC). In these models, the degradation of a bioresorbable composite is described with four parameters: the non-catalytic and auto-catalytic polymer degradation rates, $k_1$ and $k_2'$ respectively and the ceramic dissolution rate and exponent, $A_\text{d}$ and $\theta$ respectively. A comprehensive data mining exercise was carried out by surveying the existing literature in order to obtain quantitative degradation data for bioresorbable composites containing TCP, HA and CC. This resulted in a database with a variety of case studies. Subsequently, each case study was analysed using the corresponding ceramic-specific model returning a set of values for the four degradation constants. Both cases with agreement and disagreement between model prediction and experimental data were studied. 76% of the 107 analysed case studies displayed the expected behaviour. In general terms, the analysis of the harvested data with the models showed that a wide range of degradation behaviours can be attained using different polymeric matrix - ceramic filler combinations. Furthermore, the existence of discrepancies in degradation behaviour between a priori similar bioresorbable composites became apparent, highlighting the high number of hidden factors affecting composite degradation such as polymer tacticity or ceramic impurities. The analysis of the case studies also highlighted that the ceramic dissolution rate needed to depict the portrayed degradation behaviours is significantly higher than that reported for ceramics alone in dissolution studies under physiological conditions, indicating that studies of the filler elements alone do not provide a complete picture. Lastly, the computational analysis provided insight into the complex influence of factors such as sample porosity and degradation protocol in the degradation behaviour. In addition to the computational analysis of literature data, an experimental degradation study was carried out with nanocomposites made of calcium carbonate and poly(D,L-lactide-co-glycolide). This study showed the existence of a clear buering effect with the addition of the ceramic filler and confirmed the assumptions employed in the modelling framework in this particular bioresorbable composite. The detailed nature and modest size of these data enabled a more precise and thorough analysis using the CC composites degradation model. In summary, the modelling framework is able to capture the main degradation behaviour of bioresorbable composites and also point to factors responsible for dissimilar behaviours. The degradation maps generated with the values of $k_1$, $k_2'$, $A_\text{d}$ and $\theta$ output by the models appear to be a good tool to summarise, classify and facilitate the analysis and search of specific bioresorbable composites.

The ever increasing global demand for materials has placed aluminium as the world’s second most used metal, with world annual production currently >24 million tons. Consequently, the global alumina industry is perpetually striving to meet demands in conjunction with research, development and implementation of more efficient and sustainable processes and practises. Of specific concern for many proponents within the industry is that increased alumina production inadvertently results in increased Bayer Process-derived alkaline solid and liquid waste loads. Furthermore, in-house power generation at all Australian alumina refineries contributes to acid gas emissions, particularly SOx and NOx, both of which have environmental and anthropogenic impacts of global concern. The focus of this work is SO2 emission. SOx emission control measures can be achieved before, during or after combustion; the latter is termed flue gas desulphurisation (FGD). Commercially available FGD systems are dominated by once-through wet processes whereby the flue gas passes up through an absorbtion tower. The most favourable medium for industrial use is seawater, followed by limestone, and in some cases, a combination of both. However, the ever-increasing stringency of environmental emission legislation continues to inflict tighter controls on power production and is forcing industry to investigate alternative cost-effective FGD mediums. Therefore much research is currently dedicated to the utilisation of high volume, alkaline waste streams over manufactured sorbents. Modern environmental engineering approaches to waste product minimisation, neutralisation and/or reuse have lead to many new processes which change the view of many materials from waste product to environmental resource. Subsequently, this work examines the application of an isolated Bayer Process waste product, tricalcium aluminate hexahydrate (TCA6), as a FGD medium. Initial research assessed the dissolution behaviour and performance of the proposed medium with sulphuric acid, followed by batch reactor trials with a simulated flue gas. Data derived from this research indicated the suitability of TCA6 as a FGD medium and was subsequently applied to a preliminary model and proposed design parameters required for further pilot scale investigations. This work provides strong support for an economically viable and more sustainable approach to FGD for the alumina industry.

La presente tesis doctoral (i.e., “New developments in calcium phosphate bone cements: approaching spinal applications”) aporta nuevos conocimientos en el campo de los cementos óseos de fosfato de calcio (CPBCs) en relación a su aplicación clínica en el campo de la cirugía vertebral mínimamente invasiva. La hipótesis central de esta investigación fue formulada en los siguientes términos: “Los cementos apatíticos pueden ser (si se optimizan) una alternativa mejor (debido a sus propiedades de fraguado, endurecimiento y bioactividad) a los actuales cementos poliméricos utilizados en vertebroplastia y cifoplastia”. En este sentido, la presente tesis doctoral ha investigado nuevas soluciones para obtener cementos apatíticos con: (a) mejores propiedades mecánicas (Cap. 2); (b) capacidad para desarrollar macroporosidad abierta e interconectada (Cap. 3); (c) mejor estabilidad y reactividad química (Cap. 4 & 5); (d) óptimas propiedades de biocompatibilidad y osteogénicas (Cap. 6, 7 & 8); y (e) mejores propiedades de inyectabilidad (Cap. 7). Además, en esta tesis se ha investigado la aplicación de los ultrasonidos a la monitorización del fraguado inicial de cementos de base cerámica con el objetivo de relacionar la evolución de las propiedades acústicas con las características de inyectabilidad de estos cementos (Cap. 9 &10). El Capítulo 2 muestra que las propiedades mecánicas, de trabajabilidad y de fluidez de los cementos apatiticos pueden mejorarse con la adición de superplastificantes en la fase líquida de los cementos. Los resultados muestran que estos aditivos pueden mejorar la inyectabilidad inicial de los cementos sin afectar a su resistencia mecánica final. El Capítulo 3 muestra que la adición de cristales de sulfato de calcio dihidratado (CSD) a la fase en polvo de un cemento de base alfa-fosfato tricálcico (α-TCP) puede modular la formación de macroporosidad durante su fraguado. Las propiedades resultantes del fraguado de estos nuevos cementos bifásicos son debidas a la disolución del α-TCP y a la precipitación de una matriz de cristales entrecruzados de hidroxiapatita deficiente en calcio (CDHA) que contiene porosidad homogéneamente distribuida gracias a la disolución pasiva de la fase de CSD. Estos cementos bifásicos mostraron resistencias mecánicas adecuadas para la aplicación en hueso trabecular. El Capítulo 4 trata sobre la problemática del proceso de fabricación de la fase reactiva principal de los cementos apatíticos, i.e. del α-TCP (α- Ca3(PO4)2). Los resultados muestran que si la relación calcio-fosforo (Ca/P) de la mezcla reactiva inicial se desvía de la relación estequiométrica Ca/P=1.50 entonces los cementos resultantes poseen malas propiedades de fraguado y de endurecimiento. Estas desviaciones ocurren fácilmente durante el proceso de sinterización del α-TCP cuando los reactivos de mezcla utilizados varían su pureza de un lote a otro. En estos casos el α- TCP obtenido produce cementos no-reactivos, i.e. que no fraguan ni endurecen. El Capítulo 5 plantea nuevas soluciones para controlar y mejorar la reactividad química del α-TCP. En este sentido, se han estudiado nuevas soluciones sólidas sinterizadas del tipo (3.CaO-1.P2O5)1-x(FeO)x con el objetivo de reemplazar al reactivo α-TCP en las actuales formulaciones de CPBCs. Los resultados muestran que la modificación del α-TCP con hierro permite recuperar la reactividad química de cementos no-reactivos de base α-TCP con una mejora adicional de las propiedades de fraguado y reológicas de los cementos resultantes. El Capítulo 6 centra su atención sobre la citocompatibilidad de las nuevas formulaciones de cementos (investigadas en los Caps. 3-5). Los resultados mostraron que los nuevos cementos de fosfato de calcio modificados con hierro (IM-CPCs) poseen características apropiadas de citocompatibilidad ya que la adhesión y la viabilidad celular no fueron afectadas con el tiempo de cultivo por la concentración de hierro. El Capítulo 7 hace referencia a nuevas aproximaciones para mejorar la inyectabilidad de los cementos óseos de base α-TCP. Los resultados demostraron que la adición de nanopartículas de óxido de hierro en la fase en polvo de un cemento de base α-TCP mejora la inyectabilidad inicial y también la resistencia máxima a compresión del cemento sin afectar a sus reacciones físico-químicas de fraguado ni a su citocompatibilidad. El Capítulo 8 se centra sobre el carácter de citocompatibilidad, biocompatibilidad y osteogénico de los nuevos cementos bifásicos porosos/modificados con hierro (estudiados en los Caps. 3-7). Los resultados demostraron que los cementos bifásicos formulados a base de CSD y α-TCP modificado con hierro poseen la habilidad de favorecer la colonización celular in vitro y proporcionan aposición ósea firme in vivo. Se concluye que estas nuevas formulaciones tienen características de cito- y biocompatibilidad de interés como biomaterial para la sustitución/reconstrucción del tejido óseo esponjoso en aplicaciones de cirugía vertebral tales como la vertebroplastia o la cifoplastia. En el Capítulo 9 y en el Capítulo 10 se aproximan los ultrasonidos como una técnica fiable para caracterizar las propiedades iniciales de fraguado de materiales de tipo cemento. Esta técnica no-destructiva permite monitorizar el fraguado del cemento en su totalidad. Los resultados obtenidos relacionan las propiedades acústicas y de material con factores experimentales del proceso de fabricación y con características reológicas. Se concluye que la monitorización ultrasónica del fraguado de cementos óseos puede contribuir a establecer protocolos prácticos adecuados para su inyección mediante técnicas de cirugía mínimamente invasivas en cirugía vertebral. Finalmente, el Capítulo 11 presenta un resumen de los resultados más relevantes de esta investigación. / This thesis is aimed at contributing to close the gap between the research conducted on the field of calcium phosphate bone cements (CPBCs) and their specific spinal clinical use. The main working hypothesis was formulated as follows: “Apatitic cements could be (after further optimization) an alternative or better option (due to its natural setting, hardening and bioactive properties) to the present use of polymeric cements in vertebroplasty and kyphoplasty”. In this regard, this thesis has approached new solutions to obtain apatitic bone cements (ABCs) with: (a) improved mechanical properties (Chapter 2); (b) the ability to develop open-interconnected macroporosity (Chapter 3); (c) improved chemical reactivity and stability (Chapter 4 & 5); (d) suitable biocompatible and osteogenic properties (Chapter 6, 7 & 8); and (e) improved injectability properties (Chapter 7). Moreover, this thesis has also approached ultrasound in order to monitor the early setting stages of ceramic based bone cements to link acoustic and material properties with some intrinsic cement-injectability features (Chapter 9 & 10). Chapter 2 showed that workability, flowing and mechanical properties of ABCs can be improved by adding superplasticizers to the liquid cement phase. The results indicated that superplasticizers can be used to improve the injectability and the strength of apatitic bone cements. Chapter 3 showed that calcium sulfate dihydrate (CSD) crystals can be added into the cement powder phase to modulate the macroporosity of the cement during its setting. This was proved with an alpha-tricalcium phosphate (α-TCP) bone cement. The setting properties of the new biphasic cements resulted from the progressive dissolution-precipitation of α-TCP into calcium-deficient hydroxyapatite (CDHA) crystals and the passive dissolution of the CSD phase, which render porosity homogeneously distributed into an entangled matrix of CDHA crystals. The biphasic cements showed suitable strength for trabecular bone applications. Chapter 4 focused the manufacturing process of α-TCP (α-Ca3(PO4)2), the main cement reactant of most commercial ABCs. It has been shown that if calcium-to-phosphorous (Ca/P) ratio deviated from Ca/P=1.50, the resulting cements had worse setting and hardening properties. These deviations can result from sintering if reactives are not pure from batch to batch; in this case the α-TCP shows no-cement reactivity at all. Chapter 5 approached new solutions to control and improve the chemical reactivity of the α-TCP phase. In this sense, new solid solutions like (3.CaO-1.P2O5)1-x(FeO)x were investigated to replace the α-TCP of the present CPBCs. The results showed that iron modification of α-TCP recovered the chemical reactivity of unreactive α-TCP cements with even better setting and rheological end-cement properties. Chapter 6 focused the attention into the cytocompatibility of the new cement formulations (investigated previously; chapters 3-5). It is showed that the new iron-modified calcium phosphate cements (IM-CPCs) have cytocompatible features (i.e. cells’ adhesion and viability were not affected with culturing time by the iron concentration dose). Chapter 7 concerned a new approach to improve the injectability of α-TCP based bone cements. It has been shown that the addition of iron oxide nanoparticles into the powder phase of α-TCP based cement improved both, the initial injectability and maximum compressive strength of the cement without affecting their physico-chemical setting reactions and their cytocompatibility. Chapter 8 pointed to the cytocompatibility, the biocompatibility and the osteogenic character of new biphasic porous/iron-modified cements (investigated previously; chapters 3-7). The results showed that biphasic cements made of CSD and iron-modified α-TCP had the ability to support cellular colonization in vitro and lead firm bone binding in vivo. It is concluded that these new formulations has cyto- and biocompatible features of interest as further cancellous bone replacement biomaterial for spinal surgery applications such as vertebroplasty or kyphoplasty. Chapter 9 & 10 approached ultrasound as more reliable characterisation technique of the early setting properties of bone cement-like materials than the Gillmore needles standard. This non-destructive technique allowed monitoring the whole setting period of experimental calcium sulphate and calcium phosphate bone cements. The results linked acoustic and material properties with the experimental factors studied and with cement flowing features. It is expected that, after further optimization, ultrasound monitoring should help, in combination with recent approaches that measure certain injectability characteristic for calcium-based bone cements (CBC’s), to set up good practice protocols for CBC’s injection during minimally invasive surgery. Finally, Chapter 11 presents a summary of the major findings of this thesis.

Tissue engineering is an interdisciplinary field that seeks to address the needs by applying the principles of chemistry, biology and engineering for the development of viable substitutes that restore and maintain the function of human bone and cartilage tissues. In tissue engineering, scaffolds play an important role as temporary supports for the transplantation of specific cells and tissues. In this study, poly(ester-urethane)urea (PEUU) and poly(caprolactone) (PCL) scaffolds were fabricated. Scaffolds were characterized by SEM. Porosities of scaffolds vary from 67 % to 80 %. Controlled drug delivery systems release drugs at predetermined rates for extended periods. In this study / firstly poly(lactic-co-glycolicolide/tricalcium phosphate) (PLGA/TCP) and poly(L-lactide)/tricalcium phosphate (PLLA/TCP) composites loaded with Gentamicin or Vancomycin were prepared as controlled drug delivery systems for the local treatment of osteomyelitis. The release behavior of drugs were monitored by UV-VIS spectrometer. It was shown that, Vancomycin loaded samples released higher amounts of drug than the samples loaded with Gentamicin. Secondly, porous ceramic samples were coated with PLGA and PLLA and they were loaded with dexamethasone. The release behavior of samples were monitored by UV-VIS spectrometer.The cubic ceramics released higher amounts of dexamethasone than cylindrical ceramics. When the mechanical properties of porous ceramic samples were concerned, PLLA coated samples had better mechanical properties.

ABSTRACT AN INVESTIGATION OF THE MICROSTRUCTURAL AND MECHANICAL PROPERTIES OF TRI-CALCIUM PHOSPHATES DOPED WITH ALUMINUM AND FLUORIDE IONS Tahmasebifar, Aydin M. Sc., Department of Engineering Sciences Supervisor: Assoc. Prof. Dr. Zafer Evis August / 88 Pages The aim of this study was to investigate the microstructure and mechanical properties of pure tricalcium phosphate (TCP) and tricalcium phosphates doped with aluminum (Al3+) and fluoride (F-) ions at different compositions. TCP was synthesized via precipitation method and sintered at 1100

The constitutive studies of this thesis were achieved and presented in three parts. In the first part, the effects of solid state synthesis process parameters and the impurity content of primary calcium precursor on the cement-type hydration efficiency for the conversion of &alpha / -tricalcium phosphate (Ca3(PO4)2 or &alpha / -TCP) into hydroxyapatite (Ca10-xHPO4(PO4)6-x(OH)2-x x = 0&ndash / 1, or HAp) have been investigated (at 37&deg / C). &alpha / -TCP was synthesized by thermal processing of stoichiometric amounts of calcium carbonate (CaCO3) and monetite (CaHPO4) at 1150&ndash / 1350&deg / C for 2 h. Three commercial grade CaCO3 powders of different purity were used as starting materials for the synthesis process and the resultant &alpha / -TCP products for all synthesis routes were compared in terms of the material properties and their reactivities. In the second part of the studies, &alpha / -TCP and chitosan fiber (CF) composites were prepared as injectable bone cement systems which have a potential to degrade in time to be replaced by the natural bone tissue. &alpha / -TCP/CF composites were prepared in different compositions and the effect of CF addition on cement properties were examined by mechanical and injectability tests as well as microstructural and phase analysis studies. In the third part of the studies, metal chelating property of CFs was used on development of controlled zinc release systems that can be applied in local zinc deficiency therapies of bone tissue. For this purpose, CF scaffolds were prepared by wet-spinning technique and appropriate amount of zinc was loaded to these scaffolds in regard to the zinc content of a healthy human bone tissue. Zinc release studies were performed on calcium phosphate (CaP) covered and non-covered CF scaffolds and zinc ion concentrations of the release solutions were determined by ICP-MS.