Ce travail s’inscrit dans le cadre général du développement de biomatériaux ostéoinducteurs pour la réparation de grands défauts osseux. L’étude est une contribution à la compréhension des interactions physiques et chimiques entre des céramiques phosphocalciques et deux protéines d’intérêt : la fibronectine, protéine d’adhésion cellulaire, et le VEGF (pour Vascular Endothelial Growth factor) qui est impliqué dans la vascularisation et l’amélioration de la formation osseuse.Les interactions physiques fibronectine/biocéramique ont été étudiées par spectroscopie de force afin d’évaluer l’influence de la topographie et de la composition chimique de céramiques phosphocalciques en hydroxyapatite (HA), hydroxyapatite silicatée (SiHA) et hydroxyapatite carbonatée (CHA) sur l’adhésion de la fibronectine. Les résultats obtenus par cartographie de forces mettent en évidence une absence d’incidence de la chimie des céramiques polies sur la répartition en surface et l’intensité des forces d’adhésion. En revanche ces dernières sont plus fortes au niveau des joints de grains des céramiques non polies mettant en avant une influence de la topographie de surface des matériaux modulée par la chimie.Le protocole de fonctionnalisation par le VEGF consiste en trois étapes : silanisation, addition du SM(PEG)6 et immobilisation du VEGF. Les interactions chimiques VEGF/biocéramique ont été étudiées principalement par imagerie Raman pour suivre ces étapes successives de la fonctionnalisation par le VEGF de céramiques polies en hydroxyapatite (HA) et hydroxyapatite carbonatée (CHA). Cette approche a permis de cartographier l’évolution chimique de la surface des matériaux et de mettre en évidence la distribution spatiale ainsi que les réactions préférentielles entre les molécules intermédiaires et le VEGF en fonction de la nature du substrat. / This work is ascribed within the framework of the development of osteoinductive biomaterials for the repair large bone defects. It is a contribution to the understanding of the physical and chemical interactions between phosphocalcic ceramics and two proteins of interest: fibronectin (Fn), a cell adhesion protein, and Vascular Endothelial Growth Factor (VEGF) which is involved in vascularisation and improvement of bone formation.Fibronectin/bioceramic physical interactions were studied by force spectroscopy to evaluate the influence of the topography and the chemical composition of phosphocalcic ceramics made of hydroxyapatite (HA), silicated hydroxyapatite (SiHA) and carbonated hydroxyapatite (CHA) on fibronectin adhesion. The results obtained in terms of force cartography do not indicate any impact of the polished ceramics chemistry on the surface distribution and intensity of adhesion forces. However, these forces are more intense at the level of the grain boundaries of unpolished ceramics, highlighting an influence of the topography modulated by the chemical composition.The protocol for functionalisation by VEGF consists of three steps: silanisation, addition of SM(PEG)6 and immobilisation of VEGF. VEGF/bioceramic chemical interactions were studied mainly by Raman imaging in order to follow the successive steps of the functionalisation by VEGF of the polished surface of ceramics made of hydroxyapatite (HA) and carbonated hydroxyapatite (CHA). This approach allowed to map the surface chemical changes and to point out the spatial distribution as well as the preferential reactions between the intermediate molecules and VEGF depending of the substrate.

Indiana University-Purdue University Indianapolis (IUPUI) / Brasseler USA (Savannah, GA) developed and introduced a bioceramic putty called EndoSequence Root Repair Material (ERRM) that can be used as a retrofilling material for surgical endodontics. The material is said to have many of the same chemical, physical, and biological properties as mineral trioxide aggregate (MTA), but with superior handling characteristics. The material is composed of calcium silicates, monobasic calcium phosphate, zirconium oxide, tantalum oxide, proprietary fillers, and thickening agents. ERRM is said by the manufacturer to bond to adjacent dentin, have no shrinkage, be highly biocompatible, hydrophilic, radiopaque, and antibacterial due to a high pH during setting. Investigations on the sealing properties of this material have not yet been conducted. The purpose of this study was to compare the microbial leakage of Enterococcus faecalis in teeth with root-end fillings using ProRoot MTA and Brasseler’s ERRM in a dual-chamber bacterial leakage model as described by Torabinejad and colleagues. The aim of this investigation was to compare the bacterial microleakage of these two root-end filling materials exists. Sixty-two human, single-rooted, mandibular premolars in which extraction was indicated were accessed and instrumented in an orthograde fashion with hand and rotary files. Root resection of the apical 3 mm was then completed and root-end retropreparations were created for placement of root-end filling material. Twenty-seven of these premolars had root-end fillings using ProRoot MTA and 27 had root-end fillings using ERRM. Two teeth were used as a positive control group with no root-end filling, and two other teeth were used as a negative control group and were sealed and coated with dentin bonding agent. The teeth were then evaluated for microleakage using a dual-chamber bacterial microleakage model for 40 days as described by Torabinejad and colleagues. Microleakage was determined by the presence of turbidity in the lower chamber of the apparatus and was assessed each day. Fresh samples of E. faecalis were used every three days to inoculate the apparatus and serve as a bacterial challenge for the materials. Results were recorded every day for 30 days. The outcome of interest (bacterial turbidity) and time-to-leakage (in days) were determined for each of the samples. Survival analysis was used to compare the two groups with a Kaplan-Meier plot to visualize the results and a nonparametric log-rank test for the group comparison. The microleakage of ERRM was not statistically different (p > 0.05) than leakage of ProRoot MTA when subjected to E. faecalis over the 40 day observation period. Both groups had a small number of early failures (within 4 days) and no leakage was observed for the remaining 40 days of the study. Therefore, the null hypothesis was rejected. The results of this research support the use of either of these two materials when compared with the controls. The microleakage of Brasseler’s EndoSequence Root Repair Material was at least as good as ProRoot Mineral Trioxide Aggregate when tested with E. faecalis.

Despite the recent development in PLA and PLGA based medical devices, there are still needs to further improve the mechanical performance of bioresorbable medical implants and their bioactivity. This is normally done by optimizing the filler compositions in selected groups ofbiodegradable polymer matrices. In this study, the effects of various filler levels on mechanical strength and thermal properties of PLA and PLGA composites were investigated. Composites containing different dosage of osteoconductive HAp with various particles size (0-5μm, 0-50 μm, nano size), β-TCP, bioactive glass and biodegradable Poly-L-lactide and Polylactide-glycolic acid was manufactured with melt blending, using a twin-screw extruder.The samples were investigated by Differential Scanning Calorimetry (DSC), thermo gravimetric analysis (TGA), Scanning Electron Microscopy (SEM), viscometer, three points bending machine, and Optical Microscopy (OM). The Extruder produced a porous profile. The result from TGA and SEM indicated that there was homogenous filler dispersion in the matrix after compounding.The result from DSC and Viscometer shows that there was some degradation duringcompounding. Mechanical properties of composites were modified by adding filler to matrix. The addition of Bioactive glass, as a filler, increases the degradation of the polymer matrix. The best filler that was applied is 0-5μm and nano HAp. Also in in-vitro degradation part of this thesis work, the effects of calcium phosphate materialsare investigated on degradation process.

Für das Tissue Engineering von Knochen werden poröse dreidimensionale Substrate (Scaffolds) als Zellträger benötigt, die in der vorliegenden Arbeit über keramische Technologie hergestellt wurden. Neben dem strukturierten und getrockneten Verbundwerkstoff (Grünkörper) und der Sinterkeramik wurde auch der Zwischenzustand nach Ausheizen der organischen Phase (Braunkörper) evaluiert. Bei der Herstellung blieb die Architektur der parallel orientierten Kanalporen, die über den Sol-Gel-Prozess der gerichteten ionotropen Gelbildung des Alginates erzeugt wurde, in allen Materialzuständen erhalten. Die Herstellungstechnologie wurde derart optimiert, dass die neuartigen anisotropen Scaffolds allen prinzipiell gestellten Forderungen für das Tissue Engineering entsprachen – sie waren porös mit weithin einstellbarer Porengröße, sterilisierbar, gut handhabbar unter Zellkulturbedingungen, biokompatibel und degradabel. Der unerwartete Favorit der Biomaterialentwicklung, der Braunkörper – eine nanokristalline, poröse Hydroxylapatit-Biokeramik – lag in einer ersten in vivo-Studie nach 4 Wochen integriert im Knochen vor. Die beobachtete Knochenneubildung deutete auf eine osteokonduktive Wirkung des Materials hin. Die in der vorliegenden Arbeit untersuchten Technologien und Biomaterialien bieten eine Basis für weitere Forschung und motivieren zur Weiterentwicklung und Nutzung als Scaffold für das Tissue Engineering oder Knochenersatzmaterial unter Verwendung der interessanten Architektur.

Solution combustion synthesis (SCS) with its origin at IPC department of IISc has been widely practiced for synthesis of oxide materials. It is simple and low cost process, with energy and time savings that can be used to produce homogeneous, high purity, uniformly doped, nano crystalline ceramic powders. The powders characteristics such as crystallite size and surface area are primarily governed by enthalpy, flame temperature of combustion, fuel and fuel to oxidizer ratio ( F/O). In the present work an attempt has been made to investigate the process in order to exercise a control over the phase formation and nature of the product. Initial part of the work deals with the effect of fuel to oxidizer ratio on the powder properties of binary oxides with urea as fuel. The variation of adiabatic flame temperatures are calculated theoretically for different F/O ratios according to thermodynamic concept and correlated with the observed flame temperatures. Difference in the measured flame temperature and theoretical flame temperature in the fuel rich region is explained on the basis of incomplete combustion model. The effect of decomposition temperature difference of fuel and oxidizer, solubility of reactants on exothermicity of combustion reaction taking aluminiumnitrate system for various fuels is investigated. The effect of mixed fuel approach is studied by using the urea-glycine mixed fuel system using aluminium nitrate as oxidizer and employed for successful synthesis of the gamma alumina. Further Compaction behavior of SCS nano ceramic powders is studied by using Universal testing machine and the effect of F/O ratio, on agglomeration strength, aggregation strength of powder is investigated. Very few reports can be found on usage of SCS ceramic powder for biomaterial applications. By using these investigations a pyroxene series Diopside (CaMgSi2O6) silicate material is synthesized by SCS. Effect of different fuels on Diopside (DP) phase formation is investigated. Finally the DP and DP-ZnO composites, made by using Uniaxial hot pressing are investigated for their antibacterial, cytocompatibility properties. Antibacterial activity of E.Coli bacterium of Diopside powders was dose dependent type. Results of the bioactivity investigations shown flattened MC3T3 mouse osteoblast cells and MC C2C12 Myoblast cells and linkage bridges formed between them on Diopside and DP-ZnO surfaces show cyto compatibility and MTT results showed that percentage of ZnO needs to be tailored between 0-10 in order to achieve maximum cytocompatibility coupled with antibacterial property.

Für das Tissue Engineering von Knochen werden poröse dreidimensionale Substrate (Scaffolds) als Zellträger benötigt, die in der vorliegenden Arbeit über keramische Technologie hergestellt wurden. Neben dem strukturierten und getrockneten Verbundwerkstoff (Grünkörper) und der Sinterkeramik wurde auch der Zwischenzustand nach Ausheizen der organischen Phase (Braunkörper) evaluiert. Bei der Herstellung blieb die Architektur der parallel orientierten Kanalporen, die über den Sol-Gel-Prozess der gerichteten ionotropen Gelbildung des Alginates erzeugt wurde, in allen Materialzuständen erhalten. Die Herstellungstechnologie wurde derart optimiert, dass die neuartigen anisotropen Scaffolds allen prinzipiell gestellten Forderungen für das Tissue Engineering entsprachen – sie waren porös mit weithin einstellbarer Porengröße, sterilisierbar, gut handhabbar unter Zellkulturbedingungen, biokompatibel und degradabel. Der unerwartete Favorit der Biomaterialentwicklung, der Braunkörper – eine nanokristalline, poröse Hydroxylapatit-Biokeramik – lag in einer ersten in vivo-Studie nach 4 Wochen integriert im Knochen vor. Die beobachtete Knochenneubildung deutete auf eine osteokonduktive Wirkung des Materials hin. Die in der vorliegenden Arbeit untersuchten Technologien und Biomaterialien bieten eine Basis für weitere Forschung und motivieren zur Weiterentwicklung und Nutzung als Scaffold für das Tissue Engineering oder Knochenersatzmaterial unter Verwendung der interessanten Architektur.