This thesis combines four manuscripts of which I am the first author. The first manuscript examines the phase separation process and related process parameters. This article provides detailed experimental results of the delivery and separation process. During the delivery of 40% Liquid-to-Powder-Ratio (LPR) paste, only 62[plus ou moins]3 % of the paste initially present in the 10-mL syringe could be injected. Thereafter, the remaining paste in the syringe was not amendable to injection suggesting the existence of liquid separation. The LPR of the extruded fraction of a 37% LPR paste ranged from 40.9[plus ou moins]2.0 % to 42.7[plus ou moins]2.1 %. On the other hand, a shortage of water content was measured for the paste left in the syringe. Furthermore, this shortage was gradual, ranging from 27.3[plus ou moins]1.9 % at the plunger side to 30.9[plus ou moins]1.6 % at the tip side. In addition, this article presents rheological measurements of the paste showing clearly that the limitation was not related to the viscosity of the paste but rather to the phase separation process. Specifically, the yield stresses were around 66[plus ou moins]2 Pa, 19[plus ou moins]2 Pa, and 8[plus ou moins]0 Pa for 40%, 50%, and 65% LPR suspensions, respectively. For the three studied LPRs, the viscosity rapidly dropped with an increase of shear rate to a level below 10 Pas. The second manuscript examines the possibility that fine particles migrate faster than large particles during injection, hence leading to a so-called size separation. This size separation process can be expected from the scientific literature, but had not been investigated prior to my study. In a way, the size separation is very similar to the phase separation process. An electrohydraulic system was used to control the delivery process. The result of this second study, showed no evidence of size separation. It was therefore concluded that the main mechanism underlying the limited injectability is the liquid phase filtration through the porous particles bed of the paste. The third manuscript examines the role of powder porosity ([epsilon]) and permeability. For that purpose, an electronically assisted device was used to measure the powder permeability. In this study, three powders were examined for comparison and better understanding. In addition, the powder permeability was correlated with the paste injectability. Adding 3 wt% of a fine nanosized powder to the [bêta]-TCP powder decreased the mixture permeability at a porosity of [varepsilon] = 67.5% from 6.4.10[exposant]-13 m[exposant]2 to 5.6.10[exposant]-13 m[exposant]2 and increased the injected volume fraction from 70.8[plus ou moins]1.9 % to 84.5[plus ou moins]0.9 %. The results showed clear evidence that the injectability can be improved by admixing different powders. However, permeability was not a strong predictor of the liquid separation phenomenon. The last manuscript provides a practical solution to reduce phase separation occurrence. For that purpose an ultrasonication process was suggested and applied during the delivery process to improve injectability. Specifically, sonicating the paste reduced agglomeration, decreased paste viscosity due to the shear thinning and therefore reduced phase separation. The result of the ultrasound assisted delivery was remarkably effective since it has been able to fully deliver highly concentrated paste, with minimal force exerted by hand. For instance, the injectable volume fraction of a 40% LPR paste injected with a 5-mL syringe increased significantly from 71.3[plus ou moins]0.5 % to 99.1[plus ou moins]0.9 % using 150 microns ultrasonic amplitude at a 20 kHz frequency. This chapter provides clear evidence that an electromechanical approach can be used to improve the injectability of a calcium phosphate paste. This thesis addresses an important limitation of calcium phosphate cements, namely phase separation during injection. This thesis also provides a scientific understanding and a practical solution for this problem. The electromechanical solution proposed here is one out of several possible solutions. Future work may focus on building numerical tools to help in the design of the powder and to understand the link between powder properties, rheology, syringe geometry and phase separation."--Résumé abrégé par UMI

O presente estudo teve por objetivo desenvolver um cimento reparador injetável a base de cimento Portland (CP) e, uma vez determinada a formulação deste cimento experimental (CE), avaliar suas propriedades físico-químicas, mecânicas e ópticas em comparação ao Agregado Trioxido Mineral (MTA). Partiu-se de uma mistura de CP branco e 20% de oxido de bismuto, que foi utilizada como Modelo de MTA para realização de ensaios piloto realizados para determinar a proporção po/liquido (PPL), os agentes radiopacificador, antimicrobiano, plastificante e acelerador de presa. Apos determinação dos constituintes do CE de forma a obter um material com características adequadas ao uso clinico, seu desempenho foi comparado ao MTA frente aos ensaios de injetabilidade, tempo de presa, escoamento, pH, liberação de íons cálcio e arsênio, resistência a compressão (RC), avaliação da estabilidade de cor e MEV. O cimento experimental foi totalmente injetado por meio de seringa comum acoplada a agulha 19 G, diferente do MTA (p<0,05) que atingiu a forca de injeção máxima estabelecida para o teste (100 N) com apenas 10% da massa injetada. O MTA apresentou a menor media de tempo de presa inicial e final, com diferença estatisticamente significante em relação ao CE. Enquanto o escoamento do MTA foi nulo, o CE apresentou bom escoamento segundo a norma n&ordm; 57 da ADA. Não houve diferença estatisticamente significante (p>0,05) entre o pH dos cimentos testados nos períodos de 2 h e 24 h, porem, apos 168 h, o MTA apresentou pH mais elevado, diferente estatisticamente (p<0,05) do CE. No período de 2 h, ambos os cimentos tiveram liberação semelhante de íons Ca+ (p>0,05), entretanto, após 24 h e 168 h, o CE teve liberação de Ca+ significativamente maior (p<0,05) do que o MTA. Não foi detectada liberação de íons arsênio nos cimentos avaliados. O CE apresentou maiores valores de RC que o MTA em todos os tempos estudados, com diferença estatisticamente significante (p<0,05) apos 24 h e 7 d. Ambos os cimentos apresentaram alteração de cor (&Delta;E) em níveis clinicamente inaceitáveis (&Delta;E3,3), no entanto, quando o CE foi testado sem adição de prata, apresentou (&Delta;E) semelhante (p>0,05) ao grupo controle (sem cimento). De acordo com os resultados obtidos, conclui-se que a combinação dos aditivos utilizada no estudo foi capaz de proporcionar ao cimento experimental boas propriedades, o que permitiu a obtenção de um cimento reparador injetável com atividade antimicrobiana melhorada / The aim of this study was to develop an injectable repair cement based on Portland cement (PC) and, once the formulation of this experimental cement (EC) was defined, to assess its physical-chemical, mechanical and optical properties in comparison to the Mineral Trioxide Aggregate (MTA). A mixture of white PC and 20% bismuth oxide, was used as a MTA Model to perform the pilot tests in order to choose the powder-to-liquid ratio (PLR), radiopacifier agent, antimicrobial agent, liquefier and setting accelerator for the EC. Once all the constituents of the EC were chosen and after it demonstrated to be suitable for clinical application, its performance was compared to MTA through injetability tests, setting time, flow, pH, calcium and arsenic ion release, compressive strength (CS), evaluation of color stability and SEM. The EC was fully injected through a 19G needle coupled to a common syringe, different (p <0.05) from MTA, which reached the maximum injection force (100N) with only 10% of its mass injected. The MTA had statistically significant lower initial and final setting times compared to EC. MTA did not flow, while EC showed good flow according to n&ordm; 57 ADA standard. There was no statistically significant difference (p> 0.05) between the pH of the cements after 2 h and 24 h, but after 168 h, MTA had higher pH, different (p <0.05) from EC. Regarding calcion ion release, both cements had similar results (p> 0.05) after 2 h, however, after 24 h and 168 h, Ca+2 release was significantly greater (p <0.05) for EC. Arsenic ions were not detected in any cement. The EC had higher RC values than MTA in all periods evaluated, with a statistically significant difference (p <0.05) after 24h and 7d. Both cements showed color change (&Delta;E) at clinically unacceptable levels (&Delta;E3,3), however, when the EC was tested without the addition of silver had (&Delta;E) similar (p> 0,05) to control group (without cement). According to the results, it can be concluded that the combination of additives selected in the study was able to provide good properties to the EC, allowing the obtainancy of an injectable repair cement with improved antimicrobial activity

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.

No description available.

L'implantation de matériaux pour reconstruction osseuse par des techniques chirurgicales peu invasives nécessite des substituts osseux synthétiques, résorbables, injectables et radioopaques. C'est pourquoi le contrôle des propriétés de ces matériaux est primordial. Dans ce contexte, ce travail s'intéresse à la formulation de deux ciments, l'un uniquement à base de carbonate de calcium, le second composé d'un mélange de carbonate de calcium et de phosphate de calcium en quantités égales. Le traitement des phases solides pulvérulentes de ces deux ciments par les procédés de broyage et de co-broyage a été étudié. Ces procédés permettent entre autres de diminuer la taille moyenne des particules. Un mélange intime et homogène entre les constituants de la phase solide est obtenu grâce au co-broyage et les propriétés des ciments sont très significativement améliorées. Le temps de prise est diminué et l'injectabilité de la pâte est fortement augmentée (facteur 100). Cette dernière propriété a pu être évaluée grâce à la mise au point d'un dispositif et d'un protocole de mesure adaptés à un analyseur de texture. Dans le but de visualiser par radiographie aux rayons X l'introduction du ciment injectable dans le site osseux à réparer, du strontium a été introduit en tant qu'agent de contraste radio-opacifiant. Deux voies d'ajout à la formulation du ciment ont été étudiées : la première sous forme de SrCO3 dans la phase solide, la seconde sous forme de SrCl2 dans la phase liquide. Les études réalisées montrent que le co-broyage de la phase solide contenant du SrCO3 est intéressant pour homogénéiser la dispersion de l'agent de contraste et ainsi optimiser la quantité de strontium à incorporer pour atteindre le niveau de radio-opacité requis par la norme en vigueur. De plus, il a été observé que l'ajout de SrCl2 dans la phase liquide rend la pâte plus visqueuse et diminue son injectabilité. Par ailleurs, l'étude de la dissolution de ces ciments à pH physiologique a révélé une libération lente et prolongée du strontium. Enfin, des tests cellulaires in-vitro ont été réalisés sur ces ciments ; ils mettent en évidence l'excellent comportement de cellules ostéoprogénitrices vis-à-vis de ces formulations de ciment ainsi que l'intérêt d'utiliser le sel de SrCO3 plutôt que de SrCl2. La dernière partie de ce travail concerne l'étude de la cristallisation de l'aragonite, variété polymorphe du carbonate de calcium, en présence d'ions phosphate, connus pour inhiber la cristallisation du CaCO3. Grâce à une modélisation à l'aide de la technique de croissance cristalline à composition constante permettant de se placer dans des conditions proches de celles de la prise du ciment uniquement à base de carbonate de calcium in-vivo, il a été montré que la présence d'ions phosphate, même en très faible quantité (concentration &lt; 0,5 µM) diminue à la fois la vitesse de germination et la vitesse de croissance cristalline de l'aragonite. L'ensemble de ces travaux contribue à l'optimisation des propriétés de ces ciments biomédicaux et à mieux appréhender leur comportement que ce soit au moment de leur implantation in-vivo ou de leur évolution et suivi post-opératoires. D'un point de vue fondamental, ces travaux pluridisciplinaires menés dans des conditions modèles in-vitro mais également dans le cadre d'une expérimentation in-vivo ont mis en évidence l'intérêt de confronter ces deux approches pour identifier et comprendre les phénomènes et les réactions impliqués lors de la prise des ciments à base de carbonate de calcium in-vitro et in-vivo. / Implantation of bone substitute materials using minimally invasive surgical techniques requires specific properties for the material including resorbability, injectability and adequate radio-opacity. The control of such properties of the material is of prime importance to meet a surgeon's requirements. In this context, this study deals with two different mineral cements: the first one is only composed of calcium carbonate phases and the second one is a mixture of equal amount of calcium phosphate and calcium carbonate phases. An original methodology involving complementary analytical techniques was implemented to thoroughly investigate the grinding mechanism of separated or mixed reactive powders constituting the solid phase and its effects on cement reactivity and properties. We show that co-grinding the solid phase decreases the mean size of the particles and favours both a homogeneous mixing and good contact between the components, leading to a decrease in the setting time. We also set two original protocols designed to evaluate paste injectability and phase separation during paste extrusion. Co-grinding leads to synergistic positive effects on cement injectability and radio-opacity. It allows maintaining a low and constant load during the extrusion of paste, which composition remains constant. Moreover, the cement's mechanical properties can be enhanced by lowering the L/S ratio because of the lower plastic limit. To be able to follow in situ the injection of the bone cement using X-ray radiography, strontium has been introduced as a contrast agent in the cement composition. Two different routes have been investigated: SrCO3 has been added to the solid phase or SrCl2 has been dissolved in the liquid phase. We show that co-grinding process permits to homogenise strontium distribution in the cement allowing us to optimise the minimum amount of strontium to add into the cement paste to reach the radio-opacity required by ISO 9917-1 standard. Moreover, adding SrCl2 in the liquid phase makes the cement paste more viscous and diminishes its injectability. Release tests performed on Sr-loaded cements show a sustained release of strontium at 37°C and pH 7.4. Finally, in-vitro cell tests have shown the excellent behaviour of osteoprogenitor cells, especially on cements including SrCO3. The last part of this work deals with the study of the crystallization of aragonite CaCO3 in the presence of phosphate ions, naturally present in biological fluids, to better understand the setting ability of calcium carbonate cements in-vivo. Using the constant composition crystal growth technique, we show that the presence of phosphate ions, even in very low amount (concentration &lt; 0.5 µM) diminishes both the nucleation and the crystal growth rates of aragonite. This work contributes to the optimization of the properties of calcium carbonate-based cements and a better understanding and control of their behaviours during implantation and their evolution in-vivo. From a fundamental point of view, this multidisciplinary work performed in model conditions in-vitro and completed by preliminary in-vivo experiments have underlined the interest in combining these two approaches to identify and understand the phenomena and the chemical reactions involved during the setting of biomedical cements.

L'implantation de matériaux pour reconstruction osseuse par des techniques chirurgicales peu invasives nécessite des substituts osseux synthétiques, résorbables, injectables et radioopaques. C'est pourquoi le contrôle des propriétés de ces matériaux est primordial. Dans ce contexte, ce travail s'intéresse à la formulation de deux ciments, l'un uniquement à base de carbonate de calcium, le second composé d'un mélange de carbonate de calcium et de phosphate de calcium en quantités égales. Le traitement des phases solides pulvérulentes de ces deux ciments par les procédés de broyage et de co-broyage a été étudié. Ces procédés permettent entre autres de diminuer la taille moyenne des particules. Un mélange intime et homogène entre les constituants de la phase solide est obtenu grâce au co-broyage et les propriétés des ciments sont très significativement améliorées. Le temps de prise est diminué et l'injectabilité de la pâte est fortement augmentée (facteur 100). Cette dernière propriété a pu être évaluée grâce à la mise au point d'un dispositif et d'un protocole de mesure adaptés à un analyseur de texture. Dans le but de visualiser par radiographie aux rayons X l'introduction du ciment injectable dans le site osseux à réparer, du strontium a été introduit en tant qu'agent de contraste radio-opacifiant. Deux voies d'ajout à la formulation du ciment ont été étudiées : la première sous forme de SrCO3 dans la phase solide, la seconde sous forme de SrCl2 dans la phase liquide. Les études réalisées montrent que le co-broyage de la phase solide contenant du SrCO3 est intéressant pour homogénéiser la dispersion de l'agent de contraste et ainsi optimiser la quantité de strontium à incorporer pour atteindre le niveau de radio-opacité requis par la norme en vigueur. De plus, il a été observé que l'ajout de SrCl2 dans la phase liquide rend la pâte plus visqueuse et diminue son injectabilité. Par ailleurs, l'étude de la dissolution de ces ciments à pH physiologique a révélé une libération lente et prolongée du strontium. Enfin, des tests cellulaires in-vitro ont été réalisés sur ces ciments ; ils mettent en évidence l'excellent comportement de cellules ostéoprogénitrices vis-à-vis de ces formulations de ciment ainsi que l'intérêt d'utiliser le sel de SrCO3 plutôt que de SrCl2. La dernière partie de ce travail concerne l'étude de la cristallisation de l'aragonite, variété polymorphe du carbonate de calcium, en présence d'ions phosphate, connus pour inhiber la cristallisation du CaCO3. Grâce à une modélisation à l'aide de la technique de croissance cristalline à composition constante permettant de se placer dans des conditions proches de celles de la prise du ciment uniquement à base de carbonate de calcium in-vivo, il a été montré que la présence d'ions phosphate, même en très faible quantité (concentration &lt; 0,5 µM) diminue à la fois la vitesse de germination et la vitesse de croissance cristalline de l'aragonite. L'ensemble de ces travaux contribue à l'optimisation des propriétés de ces ciments biomédicaux et à mieux appréhender leur comportement que ce soit au moment de leur implantation in-vivo ou de leur évolution et suivi post-opératoires. D'un point de vue fondamental, ces travaux pluridisciplinaires menés dans des conditions modèles in-vitro mais également dans le cadre d'une expérimentation in-vivo ont mis en évidence l'intérêt de confronter ces deux approches pour identifier et comprendre les phénomènes et les réactions impliqués lors de la prise des ciments à base de carbonate de calcium in-vitro et in-vivo. / Implantation of bone substitute materials using minimally invasive surgical techniques requires specific properties for the material including resorbability, injectability and adequate radio-opacity. The control of such properties of the material is of prime importance to meet a surgeon's requirements. In this context, this study deals with two different mineral cements: the first one is only composed of calcium carbonate phases and the second one is a mixture of equal amount of calcium phosphate and calcium carbonate phases. An original methodology involving complementary analytical techniques was implemented to thoroughly investigate the grinding mechanism of separated or mixed reactive powders constituting the solid phase and its effects on cement reactivity and properties. We show that co-grinding the solid phase decreases the mean size of the particles and favours both a homogeneous mixing and good contact between the components, leading to a decrease in the setting time. We also set two original protocols designed to evaluate paste injectability and phase separation during paste extrusion. Co-grinding leads to synergistic positive effects on cement injectability and radio-opacity. It allows maintaining a low and constant load during the extrusion of paste, which composition remains constant. Moreover, the cement's mechanical properties can be enhanced by lowering the L/S ratio because of the lower plastic limit. To be able to follow in situ the injection of the bone cement using X-ray radiography, strontium has been introduced as a contrast agent in the cement composition. Two different routes have been investigated: SrCO3 has been added to the solid phase or SrCl2 has been dissolved in the liquid phase. We show that co-grinding process permits to homogenise strontium distribution in the cement allowing us to optimise the minimum amount of strontium to add into the cement paste to reach the radio-opacity required by ISO 9917-1 standard. Moreover, adding SrCl2 in the liquid phase makes the cement paste more viscous and diminishes its injectability. Release tests performed on Sr-loaded cements show a sustained release of strontium at 37°C and pH 7.4. Finally, in-vitro cell tests have shown the excellent behaviour of osteoprogenitor cells, especially on cements including SrCO3. The last part of this work deals with the study of the crystallization of aragonite CaCO3 in the presence of phosphate ions, naturally present in biological fluids, to better understand the setting ability of calcium carbonate cements in-vivo. Using the constant composition crystal growth technique, we show that the presence of phosphate ions, even in very low amount (concentration &lt; 0.5 µM) diminishes both the nucleation and the crystal growth rates of aragonite. This work contributes to the optimization of the properties of calcium carbonate-based cements and a better understanding and control of their behaviours during implantation and their evolution in-vivo. From a fundamental point of view, this multidisciplinary work performed in model conditions in-vitro and completed by preliminary in-vivo experiments have underlined the interest in combining these two approaches to identify and understand the phenomena and the chemical reactions involved during the setting of biomedical cements.