O objetivo do presente estudo foi desenvolver e avaliar um Objeto Virtual de Aprendizagem (OVA) sobre agentes de cimentação com ênfase no Cimento de Fosfato de Zinco (CFZ) e verificar a sua influência no conhecimento teórico e habilidade prática em estudantes de graduação em Odontologia. Foram descritas a metodologia e as ferramentas necessárias para o desenvolvimento do OVA. Foi criado um questionário de avaliação pedagógica e técnica do OVA utilizando a escala Likert (0 nunca e 4 sempre). O OVA foi aplicado em 46 estudantes de graduação em odontologia que foram randomizada em 4 grupos: OVA Imediato (GIOVA n=9), OVA longitudinal (GLOVA n=15) e dois grupos controles sem OVA (GIC n=9 and GLC n=13). Os grupos imediatos tiveram acesso ao OVA ou livro por 20 minutos antes do teste de habilidade, enquanto os grupos longitudinais tiveram acesso por 15 dias. O desenvolvimento do objeto permitiu a criação de uma simulação virtual da manipulação do CFZ. O questionário de avaliação mostrou que aproximadamente 65% dos alunos deram 4 pontos e 14,85% deram 3 pontos. O software utilizado foi capaz de reunir as mídias em um OVA, sendo que esse objeto com simulação virtual sobre o CFZ possui alta taxa de aprovação entre os alunos de odontologia. Um pré e pós-teste de conhecimento teórico e dois testes laboratoriais foram realizados por todos os grupos e avaliados por examinadores cegos. Os estudantes que utilizaram o OVA obtiveram melhores resultados nos testes de habilidade do que seus controles. O pós-teste de conhecimento mostrou diferença estatística nos grupos longitudinais GLC (6.0±1.15) e GLOVA (7.33±1.43). Menor espessura de película foi encontrada com diferença estatística nos grupos que utilizaram o OVA: (GIC 25±9,3) e GIOVA (16,24±5,17); GLC (50±27,08) e GLOVA (22,5±9,65). Os grupos que utilizaram o OVA obtiveram maior tempo de presa do que seus controles, e o grupo imediato mostrou diferença estatística GIC (896±218,90) e GIOVA (1138,5±177,95). O OVA com simulação virtual sobre o CFZ possui alta taxa de aprovação entre os alunos de odontologia. O CFZ manipulado por estudantes que utilizaram o OVA tiveram melhores propriedades mecânicas nos testes laboratoriais. Portanto, os grupos que utilizaram o OVA obtiveram melhor habilidade clínica que seus controles e maior retenção de conhecimento após 15 dias. / The aim of this study was to develop and evaluate a Virtual Learning Object (VLO) on cementing agents with emphasis on Zinc Phosphate Cement (ZPC), verifying its influence in theoretical knowledge and practical ability of dentistry undergraduates. The methodology and tools needed to develop the VLO were described and a pedagogical and technique assessment using the Likert Scale (0 never and 4 always) about the object was created. The VLO was applied to 46 dentistry undergraduates randomized into 4 groups: immediate VLO (GIOVA n=9), longitudinal VLO (GLOVA n=15) and two control groups without VLO (GIC n=9 and GLC n=13). Immediate groups had access to VLO or book for 20 minutes before the skill test, while the longitudinal groups had access to VLO or book for 15 days. The development of the object allowed the creation of a virtual simulation of ZPC manipulation. The questionnaire indicates that, approximately, 65% of students gave 4 points to VLO and 14.85% gave 3 points to it. The software used to construct the VLO enables to gather all media in one object, including the virtual simulation on the ZPC, that has a high approval rating among dentistry undergraduates. Pre and post test theoretical knowledge and two laboratory skill tests were performed by all groups and evaluated by blinded examiners. Students who used the VLO obtained better results in skill tests than their controls. Theoretical knowledge showed statistically significant differences in post-test of longitudinal groups: GLC (6.0 ± 1.15) and GLOVA(7:33 ± 1.43). VLO groups achieved a smaller film thickness in the skill test with statistical difference: (GIC 25 ± 9.3) and GIOVA (16.24 ± 5.17); GLC (50 ± 27.08) and GLOVA (22.5 ± 9.65). The higher setting time occurred in the VLO groups, and the immediate group showed a significant difference: GIC (896 ± 218.90) and GIOVA (1138.5 ± 177.95). The VLO with virtual simulation on ZPC has high approval rating among dentistry undergraduates. The ZPC manipulated by students who used the VLO had better mechanical properties in laboratory tests. Therefore, the groups that used the VLO had better clinical skills than their controls and greater retention of knowledge after 15 days.

Os cimentos de fosfato de cálcio (CFCs) têm atraído grande interesse para uso em ortopedia e odontologia como substitutos para partes danificadas do sistema esquelético, mostrando boa biocompatibilidade e osteointegração, permitindo sua utilização como enxerto ósseo. As características que determinam os CFCs biomateriais atrativos para a reconstituição ou remodelação óssea, são a facilidade de manipulação e moldagem, sem ter de dar forma prévia ao implante, adaptando-se totalmente à forma da cavidade óssea. Diversos estudos, têm mostrado que a adição de aditivos poliméricos tem uma forte influência sobre as propriedades do cimento. A baixa resistência mecânica é o principal obstáculo a uma maior utilização de CFC como material de implante. O objetivo deste trabalho foi avaliar as propriedades de um cimento com base em α-fosfato tricálcico (α -TCP ), adicionado de PVA (poli (álcool vinílico)) (10%, 8%, 6%), hidrogel de PVA (10%,8%,6%) reticulado com ácido cítrico (10%), hidrogel de alginato de sódio (2%) e poliacrilato de amônia (1%), todos em massa, foram adicionados ao pó de α -TCP sintetizado. As amostras foram moldadas e avaliadas quanto à densidade, porosidade, teste ―in vitro‖ (Simulated Body Fluid), fases cristalinas e propriedades mecânicas. Os resultados mostram o aumento das propriedades mecânicas do cimento, quando adicionado destes polímeros. A reticulação dos hidrogéis de PVA com ácido cítrico foi eficiente.O hidrogel de PVA, o hidrogel de alginato de sódio e o poliacrilato de amônia agiram como redutor de líquido. / The calcium phosphate cements (CPCs) have great interest for use in orthopedics and dentistry as replacements for damaged parts of the skeletal system, showing good biocompatibility and osseointegration, allowing its use as a bone graft. The characteristics that determine CPCs attractive biomaterials for bone remodeling or rebuilding, is ease of handling and molding, without having to shape prior to implantation, adapting itself fully to the shape of the bone cavity. Several studies in literature have shown that the addition of polymeric additives has a strong influence on the mechanical properties of cement. The low mechanical strength is the main impediment to a broader use of calcium phosphate bone cement as implant material. The aim of this work was evaluate the strength of a CPC based on α-tricalcium phosphate, with polymeric additions. CPC was synthesized and PVA (poli (vinyl alcohol)) (10%, 8%, 6%), sodium alginate hydrogel (2%) and ammonium polyacrylate (1%), all by weight, were added to the powder. Specimens were molded and evaluated for density, porosity, in vitro test (Simulated Body Fluid), crystalline phases and mechanical properties. The results show the increase of the mechanical properties of cement when added of polymeric additives. The crosslinking of PVA hydrogels with citric acid was effective. The PVA hydrogel, the hydrogel sodium alginate and ammonium polyacrylate acted as a reducing liquid.

O objetivo do presente estudo foi desenvolver e avaliar um Objeto Virtual de Aprendizagem (OVA) sobre agentes de cimentação com ênfase no Cimento de Fosfato de Zinco (CFZ) e verificar a sua influência no conhecimento teórico e habilidade prática em estudantes de graduação em Odontologia. Foram descritas a metodologia e as ferramentas necessárias para o desenvolvimento do OVA. Foi criado um questionário de avaliação pedagógica e técnica do OVA utilizando a escala Likert (0 nunca e 4 sempre). O OVA foi aplicado em 46 estudantes de graduação em odontologia que foram randomizada em 4 grupos: OVA Imediato (GIOVA n=9), OVA longitudinal (GLOVA n=15) e dois grupos controles sem OVA (GIC n=9 and GLC n=13). Os grupos imediatos tiveram acesso ao OVA ou livro por 20 minutos antes do teste de habilidade, enquanto os grupos longitudinais tiveram acesso por 15 dias. O desenvolvimento do objeto permitiu a criação de uma simulação virtual da manipulação do CFZ. O questionário de avaliação mostrou que aproximadamente 65% dos alunos deram 4 pontos e 14,85% deram 3 pontos. O software utilizado foi capaz de reunir as mídias em um OVA, sendo que esse objeto com simulação virtual sobre o CFZ possui alta taxa de aprovação entre os alunos de odontologia. Um pré e pós-teste de conhecimento teórico e dois testes laboratoriais foram realizados por todos os grupos e avaliados por examinadores cegos. Os estudantes que utilizaram o OVA obtiveram melhores resultados nos testes de habilidade do que seus controles. O pós-teste de conhecimento mostrou diferença estatística nos grupos longitudinais GLC (6.0±1.15) e GLOVA (7.33±1.43). Menor espessura de película foi encontrada com diferença estatística nos grupos que utilizaram o OVA: (GIC 25±9,3) e GIOVA (16,24±5,17); GLC (50±27,08) e GLOVA (22,5±9,65). Os grupos que utilizaram o OVA obtiveram maior tempo de presa do que seus controles, e o grupo imediato mostrou diferença estatística GIC (896±218,90) e GIOVA (1138,5±177,95). O OVA com simulação virtual sobre o CFZ possui alta taxa de aprovação entre os alunos de odontologia. O CFZ manipulado por estudantes que utilizaram o OVA tiveram melhores propriedades mecânicas nos testes laboratoriais. Portanto, os grupos que utilizaram o OVA obtiveram melhor habilidade clínica que seus controles e maior retenção de conhecimento após 15 dias. / The aim of this study was to develop and evaluate a Virtual Learning Object (VLO) on cementing agents with emphasis on Zinc Phosphate Cement (ZPC), verifying its influence in theoretical knowledge and practical ability of dentistry undergraduates. The methodology and tools needed to develop the VLO were described and a pedagogical and technique assessment using the Likert Scale (0 never and 4 always) about the object was created. The VLO was applied to 46 dentistry undergraduates randomized into 4 groups: immediate VLO (GIOVA n=9), longitudinal VLO (GLOVA n=15) and two control groups without VLO (GIC n=9 and GLC n=13). Immediate groups had access to VLO or book for 20 minutes before the skill test, while the longitudinal groups had access to VLO or book for 15 days. The development of the object allowed the creation of a virtual simulation of ZPC manipulation. The questionnaire indicates that, approximately, 65% of students gave 4 points to VLO and 14.85% gave 3 points to it. The software used to construct the VLO enables to gather all media in one object, including the virtual simulation on the ZPC, that has a high approval rating among dentistry undergraduates. Pre and post test theoretical knowledge and two laboratory skill tests were performed by all groups and evaluated by blinded examiners. Students who used the VLO obtained better results in skill tests than their controls. Theoretical knowledge showed statistically significant differences in post-test of longitudinal groups: GLC (6.0 ± 1.15) and GLOVA(7:33 ± 1.43). VLO groups achieved a smaller film thickness in the skill test with statistical difference: (GIC 25 ± 9.3) and GIOVA (16.24 ± 5.17); GLC (50 ± 27.08) and GLOVA (22.5 ± 9.65). The higher setting time occurred in the VLO groups, and the immediate group showed a significant difference: GIC (896 ± 218.90) and GIOVA (1138.5 ± 177.95). The VLO with virtual simulation on ZPC has high approval rating among dentistry undergraduates. The ZPC manipulated by students who used the VLO had better mechanical properties in laboratory tests. Therefore, the groups that used the VLO had better clinical skills than their controls and greater retention of knowledge after 15 days.

O objetivo do presente estudo foi desenvolver e avaliar um Objeto Virtual de Aprendizagem (OVA) sobre agentes de cimentação com ênfase no Cimento de Fosfato de Zinco (CFZ) e verificar a sua influência no conhecimento teórico e habilidade prática em estudantes de graduação em Odontologia. Foram descritas a metodologia e as ferramentas necessárias para o desenvolvimento do OVA. Foi criado um questionário de avaliação pedagógica e técnica do OVA utilizando a escala Likert (0 nunca e 4 sempre). O OVA foi aplicado em 46 estudantes de graduação em odontologia que foram randomizada em 4 grupos: OVA Imediato (GIOVA n=9), OVA longitudinal (GLOVA n=15) e dois grupos controles sem OVA (GIC n=9 and GLC n=13). Os grupos imediatos tiveram acesso ao OVA ou livro por 20 minutos antes do teste de habilidade, enquanto os grupos longitudinais tiveram acesso por 15 dias. O desenvolvimento do objeto permitiu a criação de uma simulação virtual da manipulação do CFZ. O questionário de avaliação mostrou que aproximadamente 65% dos alunos deram 4 pontos e 14,85% deram 3 pontos. O software utilizado foi capaz de reunir as mídias em um OVA, sendo que esse objeto com simulação virtual sobre o CFZ possui alta taxa de aprovação entre os alunos de odontologia. Um pré e pós-teste de conhecimento teórico e dois testes laboratoriais foram realizados por todos os grupos e avaliados por examinadores cegos. Os estudantes que utilizaram o OVA obtiveram melhores resultados nos testes de habilidade do que seus controles. O pós-teste de conhecimento mostrou diferença estatística nos grupos longitudinais GLC (6.0±1.15) e GLOVA (7.33±1.43). Menor espessura de película foi encontrada com diferença estatística nos grupos que utilizaram o OVA: (GIC 25±9,3) e GIOVA (16,24±5,17); GLC (50±27,08) e GLOVA (22,5±9,65). Os grupos que utilizaram o OVA obtiveram maior tempo de presa do que seus controles, e o grupo imediato mostrou diferença estatística GIC (896±218,90) e GIOVA (1138,5±177,95). O OVA com simulação virtual sobre o CFZ possui alta taxa de aprovação entre os alunos de odontologia. O CFZ manipulado por estudantes que utilizaram o OVA tiveram melhores propriedades mecânicas nos testes laboratoriais. Portanto, os grupos que utilizaram o OVA obtiveram melhor habilidade clínica que seus controles e maior retenção de conhecimento após 15 dias. / The aim of this study was to develop and evaluate a Virtual Learning Object (VLO) on cementing agents with emphasis on Zinc Phosphate Cement (ZPC), verifying its influence in theoretical knowledge and practical ability of dentistry undergraduates. The methodology and tools needed to develop the VLO were described and a pedagogical and technique assessment using the Likert Scale (0 never and 4 always) about the object was created. The VLO was applied to 46 dentistry undergraduates randomized into 4 groups: immediate VLO (GIOVA n=9), longitudinal VLO (GLOVA n=15) and two control groups without VLO (GIC n=9 and GLC n=13). Immediate groups had access to VLO or book for 20 minutes before the skill test, while the longitudinal groups had access to VLO or book for 15 days. The development of the object allowed the creation of a virtual simulation of ZPC manipulation. The questionnaire indicates that, approximately, 65% of students gave 4 points to VLO and 14.85% gave 3 points to it. The software used to construct the VLO enables to gather all media in one object, including the virtual simulation on the ZPC, that has a high approval rating among dentistry undergraduates. Pre and post test theoretical knowledge and two laboratory skill tests were performed by all groups and evaluated by blinded examiners. Students who used the VLO obtained better results in skill tests than their controls. Theoretical knowledge showed statistically significant differences in post-test of longitudinal groups: GLC (6.0 ± 1.15) and GLOVA(7:33 ± 1.43). VLO groups achieved a smaller film thickness in the skill test with statistical difference: (GIC 25 ± 9.3) and GIOVA (16.24 ± 5.17); GLC (50 ± 27.08) and GLOVA (22.5 ± 9.65). The higher setting time occurred in the VLO groups, and the immediate group showed a significant difference: GIC (896 ± 218.90) and GIOVA (1138.5 ± 177.95). The VLO with virtual simulation on ZPC has high approval rating among dentistry undergraduates. The ZPC manipulated by students who used the VLO had better mechanical properties in laboratory tests. Therefore, the groups that used the VLO had better clinical skills than their controls and greater retention of knowledge after 15 days.

Os cimentos de fosfato de cálcio (CFCs) têm atraído grande interesse para uso em ortopedia e odontologia como substitutos para partes danificadas do sistema esquelético, mostrando boa biocompatibilidade e osteointegração, permitindo sua utilização como enxerto ósseo. As características que determinam os CFCs biomateriais atrativos para a reconstituição ou remodelação óssea, são a facilidade de manipulação e moldagem, sem ter de dar forma prévia ao implante, adaptando-se totalmente à forma da cavidade óssea. Diversos estudos, têm mostrado que a adição de aditivos poliméricos tem uma forte influência sobre as propriedades do cimento. A baixa resistência mecânica é o principal obstáculo a uma maior utilização de CFC como material de implante. O objetivo deste trabalho foi avaliar as propriedades de um cimento com base em α-fosfato tricálcico (α -TCP ), adicionado de PVA (poli (álcool vinílico)) (10%, 8%, 6%), hidrogel de PVA (10%,8%,6%) reticulado com ácido cítrico (10%), hidrogel de alginato de sódio (2%) e poliacrilato de amônia (1%), todos em massa, foram adicionados ao pó de α -TCP sintetizado. As amostras foram moldadas e avaliadas quanto à densidade, porosidade, teste ―in vitro‖ (Simulated Body Fluid), fases cristalinas e propriedades mecânicas. Os resultados mostram o aumento das propriedades mecânicas do cimento, quando adicionado destes polímeros. A reticulação dos hidrogéis de PVA com ácido cítrico foi eficiente.O hidrogel de PVA, o hidrogel de alginato de sódio e o poliacrilato de amônia agiram como redutor de líquido. / The calcium phosphate cements (CPCs) have great interest for use in orthopedics and dentistry as replacements for damaged parts of the skeletal system, showing good biocompatibility and osseointegration, allowing its use as a bone graft. The characteristics that determine CPCs attractive biomaterials for bone remodeling or rebuilding, is ease of handling and molding, without having to shape prior to implantation, adapting itself fully to the shape of the bone cavity. Several studies in literature have shown that the addition of polymeric additives has a strong influence on the mechanical properties of cement. The low mechanical strength is the main impediment to a broader use of calcium phosphate bone cement as implant material. The aim of this work was evaluate the strength of a CPC based on α-tricalcium phosphate, with polymeric additions. CPC was synthesized and PVA (poli (vinyl alcohol)) (10%, 8%, 6%), sodium alginate hydrogel (2%) and ammonium polyacrylate (1%), all by weight, were added to the powder. Specimens were molded and evaluated for density, porosity, in vitro test (Simulated Body Fluid), crystalline phases and mechanical properties. The results show the increase of the mechanical properties of cement when added of polymeric additives. The crosslinking of PVA hydrogels with citric acid was effective. The PVA hydrogel, the hydrogel sodium alginate and ammonium polyacrylate acted as a reducing liquid.

Ce travail porte sur le conditionnement de déchets radioactifs dans une matrice cimentaire. Il vise plus particulièrement à évaluer la compatibilité chimique entre un mortier à base de ciment phospho-magnésien et l’aluminium métallique. Dans un premier temps, les processus physico-chimiques responsables de la prise et du durcissement du ciment phospho-magnésien sont étudiés : la diffraction des rayons X (DRX), la thermogravimétrie (ATG) et la résonance magnétique nucléaire (RMN-MAS du 31P et 11B) permettent d’identifier les phases solides précipitant au cours de l’hydratation du ciment ; la spectroscopie à plasma à couplage inductif (ICP-AES), la conductimétrie et la pH-métrie apportent des informations sur la composition de la solution porale. Dans un second temps, la corrosion de l’aluminium dans des mortiers phospho-magnésiens est étudiée par suivi du potentiel d’équilibre (OCP) et par spectroscopie d’impédance électrochimique (SIE).Le ciment phospho-magnésien est préparé à partir d’oxyde de magnésium (MgO) et de dihydrogénophosphate de potassium (KH2PO4). En présence d’eau, il s’hydrate selon un processus de dissolution / précipitation. La dissolution des réactifs conduit principalement à la formation de K-struvite (MgKPO4.6H2O), précédée par celle de deux hydrates intermédiaires : la phosphorrösslerite (MgHPO4.7H2O) et la phase Mg2KH(PO4)2.15H2O. L’acide borique retarde l’hydratation du ciment en ralentissant la formation des hydrates. La précipitation initiale d’un ou plusieurs composés boratés et phosphatés amorphes ou très mal cristallisés ainsi que la stabilisation des cations en solution (magnésium, potassium) pourraient en être la cause. Par comparaison avec une matrice à base de ciment Portland, la corrosion de l’aluminium dans le mortier phospho-magnésien est fortement limitée.Le pH de la solution interstitielle, proche de la neutralité, est en effet situé dans le domaine de passivation de l’aluminium. La corrosion dépend de plusieurs paramètres : elle est favorisée pour un rapport massique eau/ciment (e/c) très supérieur à la demande chimique en eau du liant (e/c = 0.51) ainsi que par la présence d’acide borique. Au contraire, le nitrate de lithium ajouté à l’eau de gâchage agit comme un inhibiteur de corrosion. Un mécanisme de corrosion en 4 étapes permet de modéliser les diagrammes d’impédance. L’évolution de la vitesse de corrosion et de la production de dihydrogène qui lui est associée peut alors être calculée au cours du temps. Les résultats obtenus sont en bon accord avec les mesures expérimentales du dihydrogène relâché par des plaques d’aluminium enrobées dans un mortier phospho-magnésien. / This work deals with the stabilization / solidification of radioactive waste using cement.More particularly, it aims at assessing the chemical compatibility between metallic aluminum and mortars based on magnesium phosphate cement. The physical and chemical processes leading to setting and hardening of the cement are first investigated. X-ray diffraction (XRD), thermogravimetry (TGA) and nuclear magnetic resonance spectroscopy (31P and11B MAS-NMR) arefirst used to characterize the solid phases formed during hydration, while inductively coupled plasma atomic emission spectroscopy analysis (ICP-AES), electrical conductimetry and pH measurementsprovide information on the pore solution composition. Then,the corrosion of metallic aluminum in magnesium phosphate mortars is studied by monitoring the equilibrium potential and by electrochemical impedance spectroscopy (EIS).Magnesium phosphate cement is prepared from a mix of magnesium oxide (MgO) and potassium dihydrogen orthophosphate (KH2PO4). In the presence of water, hydration occurs according to a dissolution – precipitation process. The main hydrate is K-struvite (MgKPO4.6H2O). Its precipitation is preceded by that of two transient phases: phosphorrösslerite (MgHPO4.7H2O) and Mg2KH(PO4)2.15H2O. Boric acid retards cement hydration by delaying theformation of cement hydrates. Two processes may be involved in this retardation: the initial precipitation of amorphous or poorly crystallized minerals containing boron and phosphorus atoms, and/or the stabilization of cations (Mg2+, K+) in solution.As compared with a Portland cement-based matrix, corrosion of aluminum is strongly limited in magnesium phosphate mortar. The pore solution pH is close to neutrality and falls within the passivation domain of aluminum. Corrosion depends on several parameters: it is promoted by a water-to-cement ratio (w/c) significantly higher than the chemical water demand of cement (w/c = 0.51), and by the addition of boric acid. On the contrary, lithium nitrate, dissolved in the mixing solution, acts as a corrosion inhibitor.A 4-step mechanism makes it possible to model the impedance diagrams. The evolution of the corrosion rate and of the amount of dihydrogen released with ongoing hydration is then calculated The results are in good agreement with the experimental determination of the H2 production by aluminum sheets embedded in magnesium phosphate mortar.

Ce travail porte sur la mise au point, le développement et l’étude de la dégradation et de la biocompatibilité d’un nouveau ciment phosphocalcique modifié par ajout de strontium. Un ciment composite formé par l’insertion de microsphère de PLAGA a aussi été développé. Ces ciments ont un intérêt thérapeutique en orthopédie et en chirurgie maxillo-faciale pour le comblement ou le renforcement osseux. Les caractéristiques mécaniques, rhéologiques et radiologiques du ciment et du composite ont été évaluées et optimisées pour rendre leurs formulations à la fois résistantes, injectables et radio-opaque. Un travail de développement à été mené pour répondre au mieux au cahier des charges clinique de ce type de substitut osseux. La chimie de la réaction au sein du ciment à été étudiée pour connaître les mécanismes réactionnels, l’évolution et le produit final de la réaction de prise. Des tests in vitro sur la dégradation par dissolution passive des constituants du ciment et du composite ont été réalisés ainsi que l’étude de la biocompatibilité sur des cultures cellulaires. Des expérimentations animales sur la peau de souris et sur le tibia de lapin ont permis de confirmer la biocompatibilité du ciment et du composite et de donner une première évaluation de sa résorption et de son remplacement par du tissu osseux néo formé. / The aim of this thesis is to design and develop a new calcium phosphate cement modified by addition of strontium and a composite cement formed by the insertion of PLAGA microspheres.These cements have a therapeutic interest in orthopaedic and maxillofacial surgery for bone filling or reinforcement.The mechanical, rheological and radiological properties of cement and composite were evaluated and optimized to improve their mechanical strength, injectability and radio-opacity. Development works were conducted to meet clinical specifications required for this type of bone substitute.The cement chemistry was studied to determine the reaction mechanisms, evolution and the final product of the setting reaction. In vitro tests on the degradation of cement components and composites were performed and the biocompatibility was studied by cell cultures.Animal experiments on mouse skin and rabbit tibia have confirmed the biocompatibility of these cements and provide a preliminary assessment of its resorption and replacement by newly formed bone tissue.

Os cimentos de fosfato de cálcio (CFCs) têm atraído grande interesse para uso em ortopedia e odontologia como substitutos para partes danificadas do sistema esquelético, mostrando boa biocompatibilidade e osteointegração, permitindo sua utilização como enxerto ósseo. As características que determinam os CFCs biomateriais atrativos para a reconstituição ou remodelação óssea, são a facilidade de manipulação e moldagem, sem ter de dar forma prévia ao implante, adaptando-se totalmente à forma da cavidade óssea. Diversos estudos, têm mostrado que a adição de aditivos poliméricos tem uma forte influência sobre as propriedades do cimento. A baixa resistência mecânica é o principal obstáculo a uma maior utilização de CFC como material de implante. O objetivo deste trabalho foi avaliar as propriedades de um cimento com base em α-fosfato tricálcico (α -TCP ), adicionado de PVA (poli (álcool vinílico)) (10%, 8%, 6%), hidrogel de PVA (10%,8%,6%) reticulado com ácido cítrico (10%), hidrogel de alginato de sódio (2%) e poliacrilato de amônia (1%), todos em massa, foram adicionados ao pó de α -TCP sintetizado. As amostras foram moldadas e avaliadas quanto à densidade, porosidade, teste ―in vitro‖ (Simulated Body Fluid), fases cristalinas e propriedades mecânicas. Os resultados mostram o aumento das propriedades mecânicas do cimento, quando adicionado destes polímeros. A reticulação dos hidrogéis de PVA com ácido cítrico foi eficiente.O hidrogel de PVA, o hidrogel de alginato de sódio e o poliacrilato de amônia agiram como redutor de líquido. / The calcium phosphate cements (CPCs) have great interest for use in orthopedics and dentistry as replacements for damaged parts of the skeletal system, showing good biocompatibility and osseointegration, allowing its use as a bone graft. The characteristics that determine CPCs attractive biomaterials for bone remodeling or rebuilding, is ease of handling and molding, without having to shape prior to implantation, adapting itself fully to the shape of the bone cavity. Several studies in literature have shown that the addition of polymeric additives has a strong influence on the mechanical properties of cement. The low mechanical strength is the main impediment to a broader use of calcium phosphate bone cement as implant material. The aim of this work was evaluate the strength of a CPC based on α-tricalcium phosphate, with polymeric additions. CPC was synthesized and PVA (poli (vinyl alcohol)) (10%, 8%, 6%), sodium alginate hydrogel (2%) and ammonium polyacrylate (1%), all by weight, were added to the powder. Specimens were molded and evaluated for density, porosity, in vitro test (Simulated Body Fluid), crystalline phases and mechanical properties. The results show the increase of the mechanical properties of cement when added of polymeric additives. The crosslinking of PVA hydrogels with citric acid was effective. The PVA hydrogel, the hydrogel sodium alginate and ammonium polyacrylate acted as a reducing liquid.

This research project presents a study of the fixation of screws in augmented and non-augmented cancellous bone at a microscopic scale. It is estimated that somewhere close to one million screws are failing each year. Therefore, the aim is to identify the key parameters affecting screw pull-out in order to improve screw fixation in cancellous bone, and hence screw design. The background for this study comes from work by Stryker, comparing screw pull-out from augmented and non-augmented cancellous bone, where a few cases of screw pull-out gave better results without bone augmentation. This is contrary to most evidence and the hypothesis to explain these results is that the screw pull-out from cancellous bone could be strongly affected by the cancellous bone micro architecture. The effect of the influence of the screw’s initial position was first verified with 2D finite element (FE) models of screw pull-out from simplified cancellous bone models. The results showed a force reaction variation up to 28% with small change in position. The hypothesis was then tested with 3D FE models of screw pull-out from more complex cancellous bone models with different volume fractions. Three volume fractions were tested and again the effects were confirmed, but only in models with the lower volume fraction. A variation up to 30% of the force reaction was observed. The 3D simplified cancellous bone models with 5.3% volume fraction were also used to study the influence of augmentation using calcium phosphate cement. A significant improvement of the screw holding power (almost 2 times) as well as an important diminution of the variability of the pull-out force due to the screw initial position was found. Other augmentation geometries were used to model cement. They all showed an increase of the screw pull-out force reaction with an increase of the cement volume. Validation of FE results was achieved by comparing screw pull-out from a cadaver cancellous bone and the FE model constructed from the same bone sample. New studies were then carried out from the cadaver cancellous bone model. The first study examined the screw initial position influence with cancellous and cortical screws and again showed that there is a strong correlation between screw pull-out stiffness and bone volume fraction. The cortical screw showed improved performance over the cancellous screw. Augmentation cases were explored using three bone samples with a range of volume fractions obtained from different sites within the cadaver bone sample. The cancellous screw was tested with 3 types of augmentation and the cortical screw was tested with one augmentation in these 3 samples. The results showed each time a significant improvement of stiffness with augmentation but when compared with the effect of volume variation inside the bone sample, it appeared that the improvement of stiffness from augmentation might not cover the loss in stiffness from a small change in bone structure. Finally, screw design parameters were investigated, as cortical screws seemed to give as good or better stiffness results than cancellous screw. The thread pitch, the thread angle and the core diameter were analysed independently and it appeared that the most important parameter was the thread pitch with an improvement of the stiffness of +46% for cancellous screws with a smaller thread pitch. The two other factors studied (core diameter and thread angle) showed somewhat stiffer results but with a relatively small influence (less than 10%). From this study, the best screw for use in cancellous bone could be a cortical screw (diameter and pitch) with thread angles similar to a cancellous screw.

Das multiple Myelom ist eine seltene maligne Knochenerkrankung bei insbesondere älteren Menschen. Dabei vermehren sich im Knochenmark in hohem Maße unkontrolliert entartete Plasmazellen. Diese Myelomzellen unterdrücken einerseits die Bildung von normalen Plasmazellen, andererseits wird das Gleichgewicht zwischen Knochenaufbau und –abbau empfindlich gestört, woraus eine erhöhte Knochenresorption resultiert. Neben den bisher angewandten Chemo- und Strahlentherapien gewinnen innovative Medikamente, wie Proteasominhibitoren und Bisphosphonate, in der Therapie an Bedeutung. Diese Medikamente reduzieren das Myelomzellwachstum und wirken hemmend auf den Knochenabbau. Durch das Auffüllen von durch Resorptionsprozesse geschädigten Knochendefekten mit wirkstoffbeladenen Calciumphosphatzementen (CPC) wird nicht nur der Knochen stabilisiert, sondern im Vergleich zur herkömmlichen oralen oder intravenösen Medikamentenverabreichung eine gezielte Freisetzung des Wirkstoffes direkt am Wirkort in wesentlich reduzierten Dosen ermöglicht. Durch die Kombination des Knochenzementes mit anderen effizienten Drug-Delivery-Systemen (DDS), wie z. B. Polymeren, kann eine optimale Anpassung der Wirkstofffreisetzung ermöglicht werden. Insbesondere haben sich bereits dendritische Polymere aufgrund ihrer globularen Struktur und Vielzahl an peripheren Funktionalitäten als besonders geeignete Wirkstoffträgersysteme herausgestellt. Bei der Anwendung im physiologischen System spielt insbesondere die Biokompatibilität dieser polymeren DDS eine entscheidende Rolle. Durch Modifizierung der peripheren Gruppen mit biokompatiblen Einheiten, wie Oligosacchariden oder Aminosäuren, kann die physiologische Verträglichkeit signifikant erhöht werden. Für die Behandlung des multiplen Myeloms am Knochen sollte in dieser Arbeit ein geeignetes dendritisches DDS auf Basis von hochverzweigtem Polyethylenimin (PEI) synthetisiert und charakterisiert werden. Das DDS sollte dabei verschiedene Anforderungen, wie eine hohe Wasserlöslichkeit und Biokompatibilität, erfüllen. Weiterhin sollten die mechanischen Eigenschaften des CPC nicht negativ beeinflusst werden und der Wirkstoff sollte effektiv vom DDS aufgenommen und kontrolliert aus dem generierten Komposit (Wirkstoff/DDS/CPC) freigesetzt werden. In der sogenannten N-Carboxyanhydrid (NCA)-Polymerisation wurden am PEI(5) (5 ≙ Mw 5 kDa) benzylgeschützte Polyglutaminsäure bzw. Polyasparaginsäureketten aufgepfropft. Durch hydrolytische Abspaltung der Schutzgruppen an den PBLG-Ketten von PEI(5)-PBLG-346 und PEI(5)-PBLA-346 erfolgte die Generierung der wasserlöslichen DDS PEI(5)-PGlu-346 und PEI(5)-PAsp-346. Die Charakterisierung der synthetisierten Kern-Schale-Architekturen PEI(5)-PBLG-346, PEI(5)-PBLA-346, PEI(5)-PGlu-346 und PEI(5)-PAsp-346 zeigte, dass nur wenige lange Polyaminosäureketten an wenigen primären und sekundären Aminogruppen des PEI(5) aufgebaut wurden. Aufgrund der noch freien primären und sekundären Aminogruppen am PEI(5) und den peripheren Aminogruppen an den Polyaminosäureketten wurden durch die Anbindung von Maltose- bzw. Laktoseeinheiten Kern-Schale-Architekturen mit einer binären Doppelschalenstrukturen erzeugt. Im Gegensatz zu reiner Polyglutaminsäure zeigten die mit Glutaminsäure modifizierten Polymerstrukturen PEI(5)-PGlu-346 und PEI(5)-PGlu-346-Mal interessante strukturelle Eigenschaften in wässriger Umgebung. Aufgrund des pH-abhängigen Ladungszustandes resultiert bei reinen Polyglutaminsäureketten normalerweise der typische Helix-Coil-Übergang. Dabei findet eine Konformationsumwandlung der α-helikalen Struktur zur ungeordneten Sekundärstruktur statt. Im Falle der PEI(5)-PGlu-346- und PEI(5) PGlu-346-Mal-Copolymere wurde jedoch keine α-helikale Konformation bei niedrigem pH-Wert nachgewiesen. Die PGlu-Ketten der wasserlöslichen Kern-Schale-Architekturen bildeten sowohl im sauren, als auch im basischen pH-Wertbereich eine ungeordnete Sekundärstruktur aus. Zusätzlich konnte nachgewiesen werden, dass die Kern-Schale-Architekturen in Abhängigkeit vom pH-Wert als isolierte Makromoleküle bzw. Aggregate mit unterschiedlich lang gestreckten Peptidketten vorliegen. Die Ursache dafür sind nicht-kovalente, intra- und intermolekular wirkende Kräfte. Zur Beurteilung der Kern-Schale-Architekturen als geeignete DDS wurde die Komplexierung des Proteasominhibitors Bortezomib (BZM) in die reinen Copolymere PEI(5)-PGlu-346, PEI(5)-PGlu-346-Mal und PEI(25)-Mal B (25 ≙ Mw 25 kDa, ohne Polyglutaminsäureketten) sowie deren Polyelektrolytkomplexe untersucht. Dabei wurden Copolymer/BZM- bzw. PEK/BZM-Komplexe in verschiedenen Verhältnissen hergestellt und die Komplexierungskapazität durch zeitabhängige Ultrafiltration UV/Vis-spektroskopisch ermittelt. Im Vergleich zu den glutaminsäuremodifizierten Copolymeren wurde durch PEI(25)-Mal B etwa doppelt so viel Wirkstoff in verschiedenen wässrigen Systemen aufgenommen. Der Grund dafür ist der größere PEI-Kern und die dementsprechend höhere Anzahl an peripheren Aminogruppen mit gebundenen Maltoseeinheiten. Die PEK zeigten im Vergleich zu den Copolymeren keine Verbesserung der Komplexierungskapazität. Um eine effektive Wirkstofffreisetzung für eine dosierte Langzeittherapie aus dem Kompositmaterial zu erhalten, ist eine stark verzögerte Freisetzung des Copolymers bzw. PEK selbst aus dem CPC notwendig. In Abhängigkeit von der Konzentration wurde für PEI(25)-Mal B eine geringere Freisetzung aus dem Copolymer/CPC- und PEK/CPC ermittelt. Aufgrund der nanoskaligen Dimension der polymeren Strukturen wird die Diffusion durch das offene CPC-Porensystem erschwert. Für die PEI(5)-PGlu-346, PEI(5)-PGlu-346-Mal und die zugehörigen PEK wurde hingegen keine messbare Freisetzung aus dem CPC nachgewiesen. Die Glutaminsäureeinheiten können Calciumionen komplexieren und beeinflussen dadurch die Keimbildung und das Wachstum der CaP-Phase. Die Copolymerstrukturen werden somit in den CPC integriert und können nur durch Abbau des schwerlöslichen Zementes freigesetzt werden. Bei den Untersuchungen der BZM-Freisetzung aus den BZM/Copolymer/CPC- und BZM/PEK/CPC-Kompositen kristallisierte sich BZM/PEI(5)-PGlu-346-Mal/CPC als effektivstes DDS heraus. Im Vergleich zum reinen BZM in CPC wurde nach 24 h nur etwa die Hälfte des Wirkstoffes aus dem Komposit freigesetzt. Weiterhin steigerte sich die Freisetzungsrate über den gesamten Zeitraum von 14 Tagen auf nur etwa 60 %. Aus dem BZM/CPC-Komposit wurden nach 14 Tagen mehr als 75 % BZM freigesetzt. In Kooperation mit der Arbeitsgruppe von Prof. Michael Gelinsky vom Zentrum für Translationale Knochen-, Gelenk- und Weichgewebeforschung (TU Dresden) wurde keine signifikante Änderung der Druckfestigkeit des CPC durch die Integration der glutaminsäuremodifizierten Copolymere festgestellt. Weiterhin wurde in in vitro-Untersuchungen mit osteogen stimulierten humanen mesenchymalen Stammzellen (hMSC) kein entscheidender Einfluss der in dieser Arbeit hergestellten PEI(5)-PGlu-346- und PEI(5)-PGlu-346-Mal-Copolymere auf die Proliferation der Zellen beobachtet. Zudem war bei beiden Copolymeren eine osteogene Differenzierung der hMSC zu knochenbildenden Osteoblasten nachweisbar, wobei PEI(5)-PGlu-346-Mal die Entwicklung der Stammzellen zu knochenbildenden Zellen sogar zu fördern scheint. Durch die Kombination von hochverzweigtem PEI mit Polyglutaminsäure und Maltose wurde in dieser Arbeit ein innovatives DDS für die kontrollierte und effektiv verzögerte Freisetzung von BZM aus CPC erzeugt, welches die einleitend erwähnten Anforderungen erfüllt. Das Copolymersystem weist eine hohe Biokompatibilität auf, ohne die mechanischen Eigenschaften des CPC zu verändern. Diese Arbeit hat daher einen entscheidenden Beitrag im Bereich der Wirkstofffreisetzung aus festen Materialien geliefert und bildet die Grundlage für zukünftige polymere DDS in CPC.