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.

<p>Extending the functional lifetime of acrylic poly(methyl methacrylate) (PMMA) bone cement may reduce the number of revision total joint replacement (TJR) surgeries performed each year. We developed a system utilizing an encapsulated water-reactive, FDA-approved tissue adhesive, 2-octyl cyanoacrylate (OCA), as a healing agent to repair microcracks within a bone cement matrix. The proposed research tested the following hypotheses: (1) reactive OCA can be successfully encapsulated and the resulting capsules thoroughly characterized; (2) the static mechanical properties of the PMMA composite can be improved or maintained through inclusion of an optimal wt% of OCA-containing capsules; (3) PMMA containing encapsulated OCA has a prolonged lifetime when compared with a capsule-free PMMA control as measured by the number of cycles to failure; and (4) the addition of capsules to the PMMA does not significantly alter the biocompatibility of the material. Based on the experiments reported herein, the primary conclusions of this dissertation are as follows: (1) functional OCA can be encapsulated within polyurethane spheres and successfully incorporated into PMMA bone cement; (2) lower wt% of capsules maintained the tensile, compressive, fracture toughness, and bending properties of the PMMA; (3) inclusion of 5 wt% of OCA-containing capsules in the matrix increased the number of cycles to failure when compared to unfilled specimens and those filled with OCA-free capsules; and (4) MG63 human osteosarcoma cell proliferation and viability were unchanged following exposure to OCA-containing PMMA when compared with a capsule-free control.</p> / Dissertation

Acrylic bone cements are one of the most important biomaterials used in orthopaedic surgery and dental applications to fill the cavities or provide mechanical interlock between prosthesis and the bone. Their biocompatibility can be increased by addition of different materials into the formulation, such as hydroxyapatite. Besides all the advantages, bone cements have several drawbacks including tissue necrosis, chemical necrosis, shrinkage of the cement and aseptic loosening. Therefore painstaking research and study are carried out on development of new formulations to improve mechanical and thermal properties as well as biocompatibilities. In this study, bone cements with different compositions were prepared and new formulations were examined to improve mechanical properties and to reduce maximum curing temperature. It was observed that addition of hydroxyapatite, while keeping polymer-to-monomer ratio constant at 2.0, decreased curing temperature and increased compressive strength about 11% (Group-C) when hydroxyapatite addition was 12%. Further addition of hydroxyapatite destroyed homogeneity of the cement dough and made it difficult to handle. The composition which contains 8% hydroxyapatite was chosen as the optimum composition in respect of mechanical properties with 102.62&deg / C curing temperature. In order to decrease the curing temperature ammonium nitrate this gives endothermic reactions with water, was added into the formulations. Addition of 0.5 g NH4NO3 decreased curing temperature from 94&deg / C to 79.3&deg / C while compressive strength kept in acceptable range with 95.99 MPa. Experiments demonstrated that the proposed formulation is acceptable for workability, homogeneity, mechanical strength and thermal properties. Further studies especially on curing temperature and biocompatibility should be achieved.

Acrylic bone cements are used in dentistry and orthopedic surgery to fix prosthetic devices into the bone. Bone cements transfer and distribute the applied load and increase the load-carrying capacity of the prosthesis/cement/bone system with the help of mechanical bonding between the device and the bone. In spite of all their advantages, bone cements have several drawbacks such as insufficient mechanical properties, high exothermic polymerization temperature, release of monomer to the environmental tissue and loosening of implant. Studies are being carried out to improve bone cement formulations with low curing temperature, good mechanical properties and good biocompatibility. In this study, bone cements with different compositions were prepared by using poly(methyl methacrylate) (PMMA) microspheres, barium sulphate (BaSO4) radiopaque agent, inorganic hydroxyapatite (HA) particles and 1-dodecyl mercaptan (DDM) chain stopping agent. Mechanical and thermal properties of the prepared bone cements were examined. When 8% hydroxyapatite was added into the formulation, both tensile and compressive strengths were increased and curing temperature was decreased. Addition of 13% BaSO4 caused 0.98% and 10.29% decrease in tensile and compressive strength values, respectively. Addition of 1%, 2% and 3% DDM, relative to the amount of methyl methacrylate monomer, decreased the maximum temperature from 101.78&deg / C to 91.80&deg / C, 78.38&deg / C and 71.35&deg / C, respectively. All compositions of the prepared bone cements fulfilled the minimum compressive strength (70 MPa) requirement and the minimum curing temperature was obtained as 71.35&deg / C. In order to have optimum desired properties, further studies to improve biocompatibility, mechanical and thermal properties of bone cements are needed.

Os cimentos de fosfato de cálcio (CFCs) formam uma pasta viscosa após a mistura de uma fase sólida (sal de fosfato de cálcio) com uma fase líquida (água ou uma solução aquosa). Esta pasta endurece, dando lugar a um precipitado que contenha um ou mais fosfatos de cálcio, que graças à sua formação à temperatura corporal evita uma resposta imunológica negativa do organismo. Embora uma das caraterísticas mais importantes dos cimentos de -TCP seja sua reabsorbilidade pelo organismo, a taxa de reabsorção In Vivo pode ser lenta devido à ausência de macroporos abertos. No presente trabalho foram obtidas estruturas macroporosas com presença de interconexões a partir da mistura de cimento de -TCP com uma fase líquida espumada. A fase líquida foi constituída de diferentes concentrações de hidrogenofosfato de sódio e um surfactante (Lutensol ON 110 ou Lauril Sulfato de Sódio), sendo espumada por agitação manual num sistema composto por 2 seringas conectadas por uma válvula de PVC. Após, foi acrescentado o pó de cimento, o qual foi misturado com a espuma no mesmo sistema. Verificou-se que as soluções com Lutensol apresentaram maior espumabilidade (218 – 400%) que as soluções com Lauril (63 – 209%). A difração de raios X evidenciou a transformação de -TCP em Hidroxiapatita deficiente em cálcio em todas as amostras após a imersão em solução de Ringer. As amostras preparadas com Lutensol apresentaram macroporos abertos com diâmetros maiores a 100m. Além disso foi observado que a macroestrutura final e o tamanho dos macroporos dos cimentos espumados varia em função das concentrações de fosfato e surfactante, além da proporção L/P. Por outro lado, a resistência a compressão das amostras macroporosas diminuiu com o aumento da porosidade total. Finalmente, foi observada a formação de uma camada continua de apatita sobre a superfície dos cimentos após imersão em SBF durante 21 dias. Este estudo sugere que as amostras de cimento de fosfato de cálcio espumadas com Lutensol possuem potencial para uso como arcabouços (scaffolds) para crescimento de tecidos. / Calcium phosphate cements (CPCs) form a viscous paste after mixing a solid phase (a calcium phosphate salt) with a liquid phase (water or an aqueous solution). This paste hardens, forming a precipitate with one or more calcium phosphates, which thanks to their formation at body temperature prevent a negative immune response. Even though one of the most important characteristics of -TCP cements is their resorbability in the body, their In Vivo resorption rate is low due to the lack of open macropores. In the present work, macroporous interconnected structures were obtained by mixing the -TCP cement with a foamed liquid phase. The liquid phase was composed of different concentrations of sodium hydrogenphosphate and a surfactant (Lutensol ON 110 or Sodium Lauril Sulfate), and it was foamed by manual agitation in a system of two syringes connected by a PVC valve. The cement powder was then added to the system and mixed with the foam likewise. Solutions with Lutensol showed better foamability (218 - 400%) than solutions with Lauril (63 - 209%). X-ray diffraction showed the transformation of -TCP into Calcium Deficient Hydroxyapatite in every sample after immersion in Ringer’s solution. Samples prepared with Lutensol showed open macropores with diameters greater than 100m. It was found that final macrostructure and size of macropores in the foamed cements vary according to phosphate and surfactant concentrations, as well as to the L/P ratio. It was also found that compressive strength of the macroporous samples decreased with the increase of the total porosity. Finally, a continuous apatite layer was observed on the surface of the cements after immersion in SBF for 21 days. This study suggests that the calcium phosphate cement samples foamed with Lutensol have potential to be applied as scaffolds for bone tissue regeneration.

[pt] O cimento ósseo ou acrílico, também conhecido por polimetilmetacrilato (PMMA), é um biomaterial empregado em cirurgias. Utilizado principalmente na fixação de próteses, além do preenchimento e reconstrução de segmentos ósseos, o cimento ósseo é colocado nos espaços vazios entre o implante e a superfície óssea endosteal, endurecendo em pouco tempo e assegurando a firme colocação da prótese ao preencher por completo o espaço vazio entre o implante e o osso. Avaliou-se a qualidade de cinco marcas de cimento ósseo comum (sem adição de antibióticos), de viscosidade normal, comercializadas no mercado brasileiro, sendo três de fabricação nacional e duas importadas, de acordo com os parâmetros da norma ABNT NBR ISO 5833. Realizou-se a inspeção visual dos componentes a fim de verificar requisitos de aparência, embalagem e rotulagem, aferição de conteúdos (massa e volume), e os seguintes ensaios para obtenção das propriedades físicas e mecânicas do material: estabilidade do componente líquido, temperatura máxima, tempo de colocação, tempo de formação de massa, intrusão, resistência à compressão e resistência e módulo de flexão. Todas as marcas foram reprovadas no item 9.1- Rotulagem da referida norma, e duas marcas, sendo uma nacional e outra importada, reprovadas nos testes de intrusão. Nas demais verificações e ensaios todas as marcas avaliadas obtiveram resultados satisfatórios. / [en] The bone or acrylic cement, also known for polymethylmethacrilate (PMMA), is a biomaterial used in surgeries. Used mainly in the fixation of prostheses, beyond the fulfilling and reconstruction of bone segments, the bone cement is placed in the empty spaces between the implant and the endosteal bone surface, hardening in little time and assuring the firm rank of prostheses when filling completely the empty space between the implantation and the bone. Quality of five marks of common bone cement (without antibiotic addition), of normal viscosity, commercialized in Brazil, was evaluated, being three of brazilian manufacture and two imported, in accordance with the parameters of norm ABNT NBR ISO 5833. They had become fullfilled it visual inspection of the components in order to verify requirements of appearance, packing and labelling, gauging of contents (mass and volume), and the following tests for attainment of the physical and mechanical properties of the material: stability of the liquid component, maximum temperature, setting time, doughing time, intrusion, compressive strength, bending modulus and bending strength. All the marks had been disapproved in the item 9.1-Labelling of the related norm, and two marks, being national and other imported, disapproved in the intrusion tests. In the too much verifications and assays all the evaluated marks had gotten resulted satisfactory.

Os cimentos de fosfato de cálcio (CFCs) formam uma pasta viscosa após a mistura de uma fase sólida (sal de fosfato de cálcio) com uma fase líquida (água ou uma solução aquosa). Esta pasta endurece, dando lugar a um precipitado que contenha um ou mais fosfatos de cálcio, que graças à sua formação à temperatura corporal evita uma resposta imunológica negativa do organismo. Embora uma das caraterísticas mais importantes dos cimentos de -TCP seja sua reabsorbilidade pelo organismo, a taxa de reabsorção In Vivo pode ser lenta devido à ausência de macroporos abertos. No presente trabalho foram obtidas estruturas macroporosas com presença de interconexões a partir da mistura de cimento de -TCP com uma fase líquida espumada. A fase líquida foi constituída de diferentes concentrações de hidrogenofosfato de sódio e um surfactante (Lutensol ON 110 ou Lauril Sulfato de Sódio), sendo espumada por agitação manual num sistema composto por 2 seringas conectadas por uma válvula de PVC. Após, foi acrescentado o pó de cimento, o qual foi misturado com a espuma no mesmo sistema. Verificou-se que as soluções com Lutensol apresentaram maior espumabilidade (218 – 400%) que as soluções com Lauril (63 – 209%). A difração de raios X evidenciou a transformação de -TCP em Hidroxiapatita deficiente em cálcio em todas as amostras após a imersão em solução de Ringer. As amostras preparadas com Lutensol apresentaram macroporos abertos com diâmetros maiores a 100m. Além disso foi observado que a macroestrutura final e o tamanho dos macroporos dos cimentos espumados varia em função das concentrações de fosfato e surfactante, além da proporção L/P. Por outro lado, a resistência a compressão das amostras macroporosas diminuiu com o aumento da porosidade total. Finalmente, foi observada a formação de uma camada continua de apatita sobre a superfície dos cimentos após imersão em SBF durante 21 dias. Este estudo sugere que as amostras de cimento de fosfato de cálcio espumadas com Lutensol possuem potencial para uso como arcabouços (scaffolds) para crescimento de tecidos. / Calcium phosphate cements (CPCs) form a viscous paste after mixing a solid phase (a calcium phosphate salt) with a liquid phase (water or an aqueous solution). This paste hardens, forming a precipitate with one or more calcium phosphates, which thanks to their formation at body temperature prevent a negative immune response. Even though one of the most important characteristics of -TCP cements is their resorbability in the body, their In Vivo resorption rate is low due to the lack of open macropores. In the present work, macroporous interconnected structures were obtained by mixing the -TCP cement with a foamed liquid phase. The liquid phase was composed of different concentrations of sodium hydrogenphosphate and a surfactant (Lutensol ON 110 or Sodium Lauril Sulfate), and it was foamed by manual agitation in a system of two syringes connected by a PVC valve. The cement powder was then added to the system and mixed with the foam likewise. Solutions with Lutensol showed better foamability (218 - 400%) than solutions with Lauril (63 - 209%). X-ray diffraction showed the transformation of -TCP into Calcium Deficient Hydroxyapatite in every sample after immersion in Ringer’s solution. Samples prepared with Lutensol showed open macropores with diameters greater than 100m. It was found that final macrostructure and size of macropores in the foamed cements vary according to phosphate and surfactant concentrations, as well as to the L/P ratio. It was also found that compressive strength of the macroporous samples decreased with the increase of the total porosity. Finally, a continuous apatite layer was observed on the surface of the cements after immersion in SBF for 21 days. This study suggests that the calcium phosphate cement samples foamed with Lutensol have potential to be applied as scaffolds for bone tissue regeneration.

Made available in DSpace on 2014-06-11T19:31:09Z (GMT). No. of bitstreams: 0 Previous issue date: 2006-05-03Bitstream added on 2014-06-13T20:27:20Z : No. of bitstreams: 1 moraes_pc_dr_jabo.pdf: 795188 bytes, checksum: 42b1e329c08d5dc84c409bddce314a86 (MD5) / Universidade Estadual Paulista (UNESP) / Foi utilizado na presente pesquisa o ultra-som pulsado de baixa intensidade, com a finalidade de avaliar, experimentalmente, seus efeitos sobre a reparação de falhas ósseas produzidas em rádio de coelhos, preenchidas ou não com o cimento de fosfato de cálcio adicionado com fibras de náilon. Foram utilizados 12 coelhos, raça Nova Zelândia, separados em dois grupos experimentais iguais (n=6) e escolhidos aleatoriamente (Grupo Tratado- GT e Grupo Controle-GC). As falhas ósseas de aproximadamente oito milímetros de extensão foram produzidas na diáfise de ambos os rádios, sendo as do membro direito preenchidas com o cimento de fosfato de cálcio sob a forma granulada e as do esquerdo, não preenchidas. Os animais do grupo tratado receberam estímulo pelo ultra-som pulsado de baixa intensidade durante 15 minutos nos primeiros cinco dias e dez minutos nos cinco dias seguintes, em ambos os membros. Os animais do grupo controle não foram estimulados pelo ultra-som. O controle radiográfico foi realizado no pós-operatório imediato e aos sete, 15 e 30 dias, de acordo com o tempo de observação de cada subgrupo (15 e 30 dias). Após o sacrifício, as áreas que continham as falhas ósseas foram processadas para a avaliação histopatológica. Os resultados das análises radiográfica e histolopatológica revelaram uma evolução mais rápida e intensa da proliferação de tecido ósseo nas falhas, preenchidas ou não pelo cimento, porém que receberam estímulo pelo ultra-som. Os resultados obtidos neste trabalho mostraram que o ultra-som pulsado de baixa intensidade é ser um recurso extremamente eficaz na aceleração do processo de ossificação e que, associado ao cimento de fosfato de cálcio com fibras de náilon, tem este processo intensificado, demonstrando, assim, o poder osteoindutor deste biomaterial. / The present experimental research evaluated the effects of low intensity pulsed ultrasound for repair bone defects produced in rabbit's radius, filled in or not with calcium phosphate cement incorporated with nylon fibers. Twelve rabbits, from the New Zealand lineage, were randomly allocated in two equal experimental groups. An eight millimeters bone gap was surgically produced in the radius bone diaphysis and filled with the cement (right radius). The left limb bone gap remained empty. Animais were submitted to dessions of pulsed ultrasonic stimulus for 15 minutes during five days and ten minutes during more five days, in both radius. Radiological examinations were performed in the immediate postoperative and seven, 15 and 30 days after surgery (according with the postoperative follow-up -15 and 30 days). The bone defects were collected and submitted to optical microscopy. The results showed an increase and faster evolution of ossification's process in the bone defects, filled or not with the bone cement, but that received stimulus by ultrasound when compared to the control group. These results suggest that low-intensity pulsed ultrasound is an effective resource for acceleration of the ossification process and, when combined with calcium phosphate cement, this effect was increased.

Cette thèse a pour objet la mesure de déformations sans contact lors d'un essai de traction à l'aide de la méthode de corrélation d'images numériques DIC (Digital Image Correlation). Cette technologie utilise le repérage d'un motif aléatoire de tachetures pour mesurer avec précision les déplacements sur une surface donnée d'un objet subissant une déformation. Plus précisément, un algorithme DIC plus efficace a été formulé, appliqué et validé. La présente thèse comporte cinq parties consacrées au développement et à la validation du nouvel algorithme DIC: (a) la formulation mathématique et la programmation, (b) la vérification numérique, (c) la validation expérimentale, par essai de traction, en comparant les mesures DIC à celles obtenues par des jauges de déformation, (d) l'étude d'un procédé d'atomisation novateur pour générer de façon reproductible le motif de tachetures pour un repérage plus exact, et (e) l'analyse des sources d'erreur dans les mesures DIC. Plus précisément, l'algorithme DIC a servi à analyser, à titre d'exemple d'application, les propriétés mécaniques du polyméthyl métacrylate utilisé pour la reconstruction du squelette. Avec l'algorithme DIC, les images d'un objet sont acquises pendant la déformation de celui-ci. On applique ensuite des techniques d'optimisation non linéaire pour suivre le motif de tachetures à la surface des objets subissant une déformation en traction avant et après le déplacement. Ce procédé d'optimisation demande un choix de valeurs de déplacement initiales. Plus l'estimation de ces valeurs de déplacement initiales est juste, plus il y a de chances que la convergence du processus d'optimisation soit efficace. Ainsi, cette thèse présente une technique de traitement novatrice reposant sur une logique floue incluant aussi l'approximation des valeurs initiales du déplacement pour démarrer un processus itératif d'optimisation, ayant pour résultat une reproduction plus exacte et efficace des déplacements et des déformations. La formulation mathématique du nouvel algorithme a été développée et ensuite mise en œuvre avec succès dans le langage de programmation MATLAB. La vérification de l'algorithme a été faite à l'aide d'images de synthèse simu­lant des déplacements de corps rigides et des déformations de traction uniformes. Plus particulièrement, les images de déplacement simulaient (1) des déplacements de 0, 1 - 1 pixel en translation, (2) des angles de rotation de 0, 5 - 5°, et (3) de grandes déformations en traction de l'ordre de 5000 à 300000µE déformation, respectivement. Les processus de vérification ont démontré que le taux d'exactitude du nouvel algorithme DIC est supérieur à 99% en ce qui concerne les mesures des différents types et niveaux de déplacements simulés. Une validation expérimentale a été menée afin d'examiner l'efficacité de la nouvelle tech­nique dans des conditions réalistes. Des échantillons de PMMA normalisés, respectant la norme ASTM F3087, ont été produits, inspectés et soumis à une charge de traction jus­qu'à la rupture. La déformation de la surface des échantillons a été mesurée au moyen (a) du nouvel algorithme DIC, et (b) des techniques utilisant des jauges de déformation de type rosette. La force maximale moyenne et la limite de résistance mécanique des quatre échantillons étaient de 880 ± 110 N et 49 ± 7 MPa, respectivement. La limite moyenne de déformation mesurée par la jauge de déformation et provenant de l'algorithme DIC étaient de 15750±2570 et 19890±3790 µs déformation, respectivement. Des déformations d'un tel ordre sont courantes pour les matériaux polymériques, et jusqu'à maintenant, la technique DIC n'n’était pas développée pour faire des mesures de déformations aussi importantes. On a constaté que l'erreur relative de la mesure DIC, par rapport à la technique de la jauge de déformation, s'élevait à 26 ± 8%. Par ailleurs, le module de Young moyen et le coefficient de Poisson moyen mesurés en utilisant des jauges de déformations étaient de 3, 78 ± 0, 07 G Pa et 0, 37 ± 0, 02, alors qu'ils étaient de 3, 16 ± 0, 61 GPa et 0, 37 ± 0, 08, respectivement lorsque mesurés avec l'algorithme DIC. L'écart croissant entre les mesures de déformation DIC et celles obtenues au moyen de jauges de déformation est probablement lié à la dis­torsion graduelle du motif de tachetures à la surface des échantillons de traction. Par la suite, on a introduit un facteur de correction de 1, 27 afin de corriger l'erreur systématique dans les mesures de déformation provenant de l'algorithme DIC. La limite de déformation des mesures DIC a été rajustée à 15712±357 µs déformation avec un taux d'erreur moyen relatif de -0, 5 ± 7, 1 %, comparé aux déformations mesurées par la jauge de déformation. Le module de Young moyen et le coefficient moyen de Poisson de l'algorithme DIC et des mesures obtenues par la jauge de déformation ont par ailleurs été rajustés à 3, 8 ± 0, 4 GPa et 0, 368 ± 0, 025, respectivement. Au moyen d'un procédé d'atomisation, des taches de peinture ont été générées de façon reproductible sur la surface d'un objet. Une approche expérimentale de planification facto­rielle a été utilisée pour étudier le motif de tachetures (répartition et gradient de l'échelle des tons de gris) pour mesurer l'exactitude de l'algorithme DIC. Plus particulièrement, neuf motifs de tachetures différents ont été générés au moyen du procédé d'atomisation et testés pour la translation et la rotation de corps rigides. Les résultats ont révélé que l'erreur moyenne relative parmi les neuf motifs de tachetures variait de 1, 1 ± 0, 3% à -6, 5 ± 3, 6%. Le motif de tachetures préféré, lequel se démarquait par une large gamme de taches claires et de valeurs de tons de gris, a produit une erreur relative de 1, 1 ± 0, 3%. Une analyse des erreurs et des sources d'erreurs relatives de la mesure de l'algorithme DIC a été menée. Ti-ois catégories de sources d'erreurs, incluant l'algorithme lui-même, les paramètres du processus (taille des sous-ensembles, nombre de pixels calculés) et l'en­vironnement physique (uniformité des échantillons, motifs de tachetures, effet thermique de la caméra CCD et distorsion de la lentille, erreur de non-linéarité dans le circuit de la jauge de déformation) ont fait l'objet d'une étude et de discussions. Enfin, des solutions ont été amenées afin d'aider à réduire les erreurs systématiques et aléatoires en lien avec les trois catégories de sources d'erreurs susmentionnées. Pour terminer, un nouvel algorithme DIC permettant une approximation plus juste de l'estimation initiale, entraînant par conséquent une convergence efficace et précise de l'op­timisation a été développé, programmé, mis en oeuvre et vérifié avec succès pour ce qui est des déformations importantes. La validation expérimentale a fait ressortir une erreur systé­matique inattendue des mesures DIC lorsque comparées aux mesures obtenues au moyen de la technique des jauges de déformation. Plus l'échantillon se déformait, plus l'erreur augmentait proportionnellement. Par conséquent, la distorsion graduelle des tachetures sur la surface de l'objet était probablement la cause de l'erreur. L'erreur étant systéma­tique, elle a été corrigée. Le procédé d'atomisation a permis de générer des tachetures de façon reproductible sur la surface d'un objet. Grâce aux mesures DIC, le comportement mécanique des polymères soumis à des déformations importantes, comme le polyméthyl métacrylate servant à la reconstruction du squelette, peut être étudié et une fois maîtrisé, servir à l'élaboration de matériaux plus efficaces. / Abstract : The present thesis is focused on the non-contact and efficient strain measurement using the Digital Image Correlation (DIC) method, which employs the tracking of random speckle pattern for accurate measurement of displacements on a surface of an object undergoing deformation. Specifically, a more efficient DIC algorithm was successfully developed, implemented, and validated. This thesis consists of five parts related to the novel DIC algorithm: (a) the development and implementation, (b) the numerical verification, (c) the experimental validation, for tensile loading, by comparing to the deformation measurements using the strain gauge technique, (d) the investigation of a novel atomization process to reproducibly generate the speckle pattern for accurate tracking, and (e) the analysis of the error sources in the DIC measurements. Specifically, the DIC algorithm was used to exemplarily examine the mechanical properties of polymethyl methacrylate (PMMA) used in skeletal reconstruction. In the DIC algorithm, images of an object are captured as it deforms. Nonlinear optimization techniques are then used to correlate the speckle on the surface of the objects before and after the displacement. This optimization process includes a choice of suitable initial displacement values. The more accurate the estimation of these initial displacement values are, the more likely and the more efficient the convergence of the optimization process is. The thesis introduced a novel, fuzzy logics based processing technique, approximation of the initial values of the displacement for initializing iterative optimization, which more accurately and efficiently renders the displacements and deformations as results. The mathematical formulation of the novel algorithm was developed and then successfully implemented into MATLAB programming language. The algorithmic verification was performed using computer-generated images simulating rigid body displacements and uniform tensile deformations. Specifically, the rigid motion images simulated (1) displacements of 0.1-1 pixel for the rigid body translation, (2) rotation angles of 0.5-5 ̊ for rigid body rotation and (3) large tensile deformations of 5000-300000µɛ, respectively. The verification processes showed that the accuracy of the novel DIC algorithm, for the simulated displacement types and levels above 99%. The experimental validation was conducted to examine the effectiveness of the novel technique under realistic testing conditions. Normalized PMMA specimens, in accordance to ASTM F3087, were produced, inspected and subjected to tensile loading until failure. The deformation of the specimen surface was measured using (a) the novel DIC, and (b) strain gauge rosette techniques. The mean maximum force and ultimate strength of four specimens were 882.2±108.3 N and 49.3±6.2 MPa, respectively. The mean ultimate deformation from the gauge and DIC groups were 15746±2567µɛ and 19887±3790µɛ, respectively. These large deformations are common in polymeric materials, and the DIC technique has thus far not been investigated for large deformation. The relative mean error of the DIC measurement, in reference to those of the strain gauge technique, was found to be up to 26.0±7.1%. Accordingly, the mean Young's modulus and Poisson's ratio of strain gauge measurement were 3.78±0.07 GPa and 0.374±0.02, and of the DIC measurements were 3.16±0.61 GPa and 0.373±0.08, respectively. The increasing difference of the DIC strain measurements relative to those of the strain gauge technique is likely related to the gradual distortion of the speckle pattern on the surface of the tensile specimen. Subsequently, a Correction Factor (CF) of 1.27 was introduced to correct for the systematic error in the deformation measurements of the DIC group. The corrected ultimate deformation of the DIC measurements became 15712±357µɛ with the relative mean error of -0.5±7.1%, if compared to those measurements of the strain gauge techniques. Correspondingly, the mean Young's Modulus and Poisson's ratio of the DIC and of the strain gauge measurements became 3.8±0.4 GPa and 0.368±0.025, respectively. Using an atomization process, paint speckles were reproducibly generated on the surface of an object. A factorial design of experiments was used to investigate the speckle pattern (grey value distribution and gradient) for the DIC measurement accuracy. Specifically, nine different speckle patterns were generated using the atomization process and tested for rigid body translation and rotation. The results showed the relative mean errors among the nine speckle patterns varied from 1.1±0.3% to -6.5±3.6%. The preferred speckle pattern, which was characterized by a wide range of sharp speckle and of grey values, produced a mean error of 1.1±0.3%. The analysis of errors and relating sources in the DIC measurement was conducted. Three categories of sources including algorithmic sources, processing parameters sources (subset size, number of pixels computed) and physical environment sources (specimen uniformity, speckle pattern, self-heating effect of the CCD camera and lens distortion of the camera, non-linearity error in strain gauge circuit) were investigated and discussed. Finally, the solutions were provided in order to help reduce the systematic and random errors relating to the aforementioned three categories of sources for errors. In conclusion, a novel DIC algorithm for a more accurate approximation of the initial guess and accordingly for an efficient and accurate convergence of the optimization was successfully formulated, developed, implemented and verified for relatively large deformations. The experimental validation surprisingly showed a systematic error of the DIC measurements, if compared to the measurements of the strain gauge technique. The larger the deformation applied to the specimen, the larger the error gradually became. Therefore, the gradual distortion of the speckles on the surface of the object was likely the underlying cause of the error. The error was systematic and therefore corrected. The atomization process allowed generating reproducible speckles on the surface of an object. Using the DIC measurements, the mechanical behavior of polymers, undergoing large deformations, such as polymethyl methacrylate used in skeletal reconstruction can be investigated and, once understood, the knowledge gained can help develop more effective materials.

O envelhecimento promove o aparecimento de doenças crônicodegenerativas, entre elas a osteoartrose. Artroplastia Total de Quadril (ATQ) tem sido procedimento comumente frequentemente com uso de cimento ósseo metilmetacrilato (MTC). Por outro lado, importantes alterações hemodinâmicas são descritas durante o procedimento de cimentação. A raquianestesia é um procedimento anestésico que produz menores efeitos hemodinâmicos e melhor analgesia pós-operatória em comparação a anestesia geral para a ATQ. Entretanto, especificamente neste procedimento cirúrgico tais alterações permanecem a ser investigadas. Buscamos avaliar os efeitos hemodinâmicos através da técnica de cardioimpedância em pacientes idosos submetidos à cirurgia de ATQ com o uso de MTC e raquianestesia. Utilizamos um estudo transversal, observacional, comparativo, inter-metodológico e com intervenção ativa. Método: Doze pacientes de ambos os sexos, > 65 anos, com indicação ortopédica para ATQ foram estudados. Os sujeitos receberam avaliação pré-anestésica e realizaram exames laboratoriais préoperatórios. Foram submetidos à cirurgia de ATQ com utilização de raquianestesia e implante de cimento de MTC. Os pacientes foram monitorados hemodinamicamente por meio da cardiografia de impedância, da saturação de oxigênio e pressão arterial, no intra-operatório, no momento acordado, durante a indução anestésica, na colocação do MTC e após este procedimento. Após a expansão volêmica observamos que houve aumento do DC quando comparado a raquianestesia, cimentação, inserção, redução da prótese e ao final da cirurgia (P<0,05). Tais resultados foram de certa forma, atenuados na presença de efedrina. No entanto, o VS sofreu alterações nos eventos supracitados na presença ou não da droga. Por outro lado, a FC, o IC e a RVS sofreu poucas alterações durante os eventos estudados. O DC, IC e o VS se correlacionaram com a massa corporal (r = 0,81, 0,60 e 0,67 respectivamente), o VS se correlacionou negativamente com a idade (r = -0.67), o IC se correlacionou negativamente com a classe funcional pela NYHA (r = -0,61) e o DC se correlacionou positivamente com a quantidade de efedrina administrada (r = 0,70). Conclusão: O procedimento cirúrgico de ATQ com MTC sob raquianestesia produz alterações hemodinâmicas e a cardioimpedância foi um instrumento útil para guiar os procedimentos e conduta do intraoperatório, configurando-se como uma técnica interessante para monitorização não invasiva. / Aging promotes the onset of chronic diseases, including osteoarthritis. Hip arthroplasty procedure has been commonly often the use of methylmethacrylate bone cement (MMA) has been used in the surgical procedure. On the other hand, significant hemodynamic changes are described in the cementation procedure. Spinal anesthesia is an anesthetic that produces less hemodynamic effects and better postoperative analgesia compared to general anesthesia for surgery arthroplasty. However, this particular surgical procedure (hip arthroplasty) such changes remain to be investigated. To evaluate the hemodynamic effects through cardioimpedance technique in elderly patients undergoing surgery for hip arthroplasty with the use of MMA for prosthetic hip and spinal. Twelve patients of both sexes, > 65 years, with orthopedic indication for hip arthroplasty were studied. The subjects received preanesthetic evaluation and underwent preoperative laboratory. From then underwent surgery for hip arthroplasty with use of spinal anesthesia and MMA cement. Patients were haemodynamically monitored by impedance cardiography, oxygen saturation and blood pressure intraoperative, when awake, during anesthesia induction, installing the MMA cement and after this procedure. After volume expansion, we observed that there was increase in CO when compared to spinal anesthesia, cementing, insertion, and reduction of the prosthesis at surgery (P<0.05). These results were somewhat attenuated in the presence of ephedrine. However, the SV underwent changes at aforementioned event on the presence or not of drugs. On the other hand, HR, CI and SVR has a few changed during the studied event. The CO, CI and the SV was correlated with body mass (r = 0.81, 0.60 and 0.67 respectively), SV was negatively correlated with age (r = -0.67), the CI was negatively correlated with NYHA functional class (r = -0.61) and CO was positively correlated with the amount of ephedrine administered (r = 0.70).Conclusion: The surgical procedure for hip arthroplasty under spinal anesthesia with MMA produces haemodynamic changes and cardioimpedance was a useful tool to guide the procedures and conduct of the intraoperative considering as interesting technique for noninvasive monitoring.