De nombreux traitements de surface (sablage, attaques acides…) ont été mis au point sur les implants dentaires afin de favoriser leur ostéointégration. Par ailleurs, depuis plusieurs années des revêtements à base de phosphates de calcium sont également développés dans le même but.L’objectif principal de la thèse est de mettre au point un procédé de revêtement à basse température afin de déposer à la surface de l’implant en titane une couche mince de phosphate de calcium, de structure et de composition analogue au minéral osseux en vue de favoriser l’ostéointégration. Il est aussi souhaité que ce revêtement présente des propriétés antibactériennes afin de lutter contre les infections post-opératoires. Dans un premier temps, un traitement de surface de l’implant en titane composé d’une étape de sablage et d’une attaque acide a été développé. Il permet d’obtenir une rugosité moyenne de surface comprise entre 1,4 et1,8 µm ainsi qu’une texture microporeuse et une mouillabilité de surface améliorée. Puis, les procédés de revêtement d’électrodéposition et d’immersions successives ont été étudiés. L’étapede centrifugation implémentée dans le procédé d’immersions successives s’est révélée cruciale et un revêtement d’environ 2 µm d’épaisseur composé d’apatite biomimétique a été obtenu. La composition et l’épaisseur du revêtement élaboré par électrodéposition est fortement influencée par la durée du dépôt. Ainsi une durée d’électrodéposition de 1 mn menée à un potentiel de -1,6V/ECS permet d’obtenir un revêtement d’environ 1,5 µm d’épaisseur composé d’une couche de phosphate octocalcique et de cristaux de brushite. Un test de vissage/dévissage dans une mâchoire artificielle a démontré la tenue mécanique des revêtements obtenus selon les deux procédés. Enfin, des ions antibactériens tels que l’argent, le cuivre ou le zinc ont été incorporésaux revêtements. Il a été démontré que des taux importants d’incorporation allant jusqu’à 40 %molaire par rapport au calcium peuvent être atteints pour le cuivre et le zinc. Des tests biologiques permettant d’évaluer l’effet de ces revêtements sur l’activité biologique de cellules mésenchymateuses humaines ainsi que sur la formation d’un biofilm (modèle de péri-implantite)en vue de la prévention des infections post-opératoires ont conduit à des résultats prometteurs pour le développement de tels revêtements bioactifs. Ces travaux de thèse s’inscrivent dans le cadre du projet BIOACTISURF, soutenu par la Région Midi-Pyrénées, et réalisé en collaboration avec le Laboratoire de Génie Chimique (LGC) ainsi qu’un partenaire industriel / Numerous surface treatments have been developed in order to improve osseointegration of dentalimplants (sandblasting, acid etching…). Moreover, various strategies involving calcium phosphate coatings have emerged for the same target for a few decades. The main purpose of this work is todevelop a low temperature process allowing the deposition of a thin calcium phosphate layer at the titanium implant surface. The composition and structure of this calcium phosphate coating have to be close to the bone mineral to enable osseointegration improvement. Moreover, thecoating should have antibacterial properties in order to prevent post-operative infections. A surfacetreatment protocol composed of sandblasting and acid etching was firstly developed creating anaverage roughness of 1.4 – 1.8 µm with micropits and improved wettability. Secondly, two processes were studied to produce the calcium phosphate coating: the alternate soaking processand the electrodeposition. It was demonstrated that the centrifugation step implemented in thealternate soaking process is crucial and a coating of about 2 µm thick composed of biomimeticapatite was obtained. Among all the operating parameters of the electrodeposition process, time ofelectrodeposition has the major impact on the composition and the thickness of the coating. An electrodeposition of 1 mn at -1.6 V/SCE leads to a 1.5 µm thick coating composed of a layer ofoctacalcium phosphate and dicalcium phosphate dihydrate crystals. A screw/unscrew test demonstrated the mechanical stability of the coatings obtained by both processes. Finally,antibacterial ions such as silver, copper and zinc were incorporated in the coatings. Highincorporation rate up to 40 mol.% compared to calcium were determined for copper and zinc.Biological tests were conducted to qualify the effect of these coatings on the biological activity ofhuman mesenchymal cells and on the formation of a biofilm (peri-implantitis model) to preventpost-operative infections. They led to promising results for the development of such bioactivecoatings. This work is part of the BIOACTISURF project, supported by the Midi-Pyrénées Region,and carried out in collaboration with the Laboratory of Chemical Engineering (LGC) and an industrial partner

<p>In two prospective, clinical studies the stability of implants and prosthetic constructions were evaluated after three years of loading. In the first study, the implant and the bridge stability of 39 patients with 1-stage bone grafts, were compared to a reference-group of 37 patients who did not need bone grafts. In the second study, 40 patients were randomised to have either 1-stage sinus inlay bloc grafts or 2-stage sinus inlay particulated grafts. </p><p>Implant success in Paper 1, was 75.3% in the study group and 93.1% in the reference group. In Paper 2 implant survival in the 1-stage group was 77.7% and 86.5% in the 2-stage group. Bruxism and post-operative complications, such as unexpected pain, dehiscence and infection were found to be associated with the later loss of implants. </p><p>The volumes of onlay block and inlay particulated bone grafts, after 6 months as evaluated by computed tomography showed the decrease of 49.5% and 47% respectively, although there was a wide range in both groups. </p><p>Using of cutting torque measurements during the placement of implants in grafted and non-grafted jaw bone, showed a significant inverse correlation to the commonly used clinical estimation of jaw bone quality, acc. to Lekholm & Zarb. Significantly lower torque values were recorded in grafted regions when compared to non-grafted. </p><p>It was shown that autogenous bone grafts and implants to the edentulous maxilla, after early high failure rates, showed stable and predictable results after three years. Bruxism was found to be significantly associated with implant failures and initially reduced biomechanical properties was seen in the grafted bone. </p>

In two prospective, clinical studies the stability of implants and prosthetic constructions were evaluated after three years of loading. In the first study, the implant and the bridge stability of 39 patients with 1-stage bone grafts, were compared to a reference-group of 37 patients who did not need bone grafts. In the second study, 40 patients were randomised to have either 1-stage sinus inlay bloc grafts or 2-stage sinus inlay particulated grafts. Implant success in Paper 1, was 75.3% in the study group and 93.1% in the reference group. In Paper 2 implant survival in the 1-stage group was 77.7% and 86.5% in the 2-stage group. Bruxism and post-operative complications, such as unexpected pain, dehiscence and infection were found to be associated with the later loss of implants. The volumes of onlay block and inlay particulated bone grafts, after 6 months as evaluated by computed tomography showed the decrease of 49.5% and 47% respectively, although there was a wide range in both groups. Using of cutting torque measurements during the placement of implants in grafted and non-grafted jaw bone, showed a significant inverse correlation to the commonly used clinical estimation of jaw bone quality, acc. to Lekholm &amp; Zarb. Significantly lower torque values were recorded in grafted regions when compared to non-grafted. It was shown that autogenous bone grafts and implants to the edentulous maxilla, after early high failure rates, showed stable and predictable results after three years. Bruxism was found to be significantly associated with implant failures and initially reduced biomechanical properties was seen in the grafted bone.

Das Ziel der vorliegenden Arbeit war es, die Wachstumsbedingung der nicht kollagenen Knochenproteine auf unterschiedlichen Konversionsoberflächen zu untersuchen. Dazu wurde das Proliferations- sowie Apoptoseverhalten der Knochenproteine in vitro bestimmt. Es kamen neben dem Probekörper Titan als Negativstandard und Ticer als Positivstandard, vier weitere Probekörper auf Titanbasis mit unterschiedlicher Kalzium-Phosphorrelation zur Anwendung. Diese wurden mit humanen Knochenzellen beschickt und über einen Zeitraum vom 3., 5., 7., und 10. Versuchstag ausgewertet. Die Zellkerne und Apoptosefragmente wurden immunhistochemisch markiert und fluoreszenzoptisch untersucht. Desweiteren wurden die relativen Grauwerte ermittelt, welche die Intensität des Bildes wiedergeben. Es zeigte sich in überwiegenden Fällen eine Zunahme der Zellanzahlen auf den verschiedenen Probekörpern. Dagegen verhielt sich die Zahl der apoptotischen Fragmente invers, indem sie auf ein Minimum absanken. In unserer Arbeit kommen wir zu der Annahme, dass Oberflächenmodifikationen die Knochenmineralisierung in der Phase der Knochenneubildung um das Implantat herum, respektive um die Oberflächenstruktur des Implantates, signifikant verbessern. Durch die Beschichtung der Implantatoberflächen mit Kalzium-Phosphor wird einerseits die Oberflächenrauigkeit erhöht, andererseits die Anbindung vom Implantat an die Knochenstruktur verbessert.

A comprehensive understanding of the interactions between orthopaedic and dental implant surfaces with the surrounding host tissue is essential in the design of advanced biomaterials that better promote bone growth and osseointegration of implants. Dental implants with roughened surfaces and high surface energy are well known to promote osteoblast differentiation in vitro and promote increased bone-to-implant contact in vivo. In addition, increased surface roughness increases osteoblasts response to the vitamin D metabolite 1α,25(OH)2D3. However, the exact mechanisms mediating cell response to surface properties and 1α,25(OH)2D3 are still being elucidated. The central aim of the thesis is to investigate whether integrin signaling in response to rough surface microtopography enhances osteoblast differentiation and responsiveness to 1α,25(OH)2D3. The hypothesis is that the integrin α5β1 plays a role in osteoblast response to surface microtopography and that 1α,25(OH)2D3 acts through VDR-independent pathways involving caveolae to synergistically enhance osteoblast response to surface roughness and 1α,25(OH)2D3. To test this hypothesis the objectives of the studies performed in this thesis were: 1) to determine if α5β1 signaling is required for osteoblast response to surface microstructure; 2) to determine if increased responsiveness to 1α,25(OH)2D3 requires the vitamin D receptor, 3) to determine if rough titanium surfaces functionalized with the peptides targeting integrins (RGD) and transmembrane proteoglycans (KRSR) will enhance both osteoblast proliferation and differentiation, and 4) to determine whether caveolae, which are associated with integrin and 1α,25(OH)2D3 signaling, are required for enhance osteogenic response to surface microstructure and 1α,25(OH)2D3. The results demonstrate that integrins, VDR, and caveolae play important roles in mediating osteoblast response to surface properties and 1α,25(OH)2D3. Silencing of the β1 integrin in osteoblast-like MG63 cells significantly reduced osteogenic response to surface topography and 1α,25(OH)2D3. Silencing of the α5 subunit did not alter the response of MG63 cells to changing surface roughness or chemistry, although future work must confirm these results given similar cell surface α5 integrin expression observed in control and α5-silenced cells. Multifunctional RGD, KRSR, and KSSR coated surfaces show that RGD increased osteoblast proliferation and reduced differentiation, KRSR had no affect on osteoblast phenotype, and KSSR increased osteoblast differentiation. These results suggest that titanium surfaces can be modified to manipulate proliferation and differentiation and that RGD/KSSR functionalized surfaces could be further investigated for use as osteointegrative surfaces. The results using VDR deficient osteoblasts demonstrate that 1α,25(OH)2D3 acts via VDR-dependent mechanisms in cells cultured on titanium surfaces that support terminal differentiation. In caveolae deficient osteoblasts, 1α,25(OH)2D3 affected cell number, alkaline phosphatase activity, and TGF-β1 levels, although levels of osteocalcin and PGE2 were not affected. These results are consistent with the hypothesis that VDR is required for the actions of 1α,25(OH)2D3, but that caveolae-dependent membrane 1α,25(OH)2D3 signaling modulates traditional VDR signaling. The exact mechanisms for this interaction remain to be shown. Overall, these results are important in better understanding the role of β1 integrin partners in mediating osteoblast response to implant surfaces and in understanding how integrin signaling can alter osteoblast differentiation and responsiveness to 1α,25(OH)2D3 via genomic and non-genomic pathways.

Objective: To appraise whether adverse events following oral implant placement may be associated with peri-operative use of non-steroidal anti-inflammatory drugs (NSAIDs). Methods: All patients with recorded implant failures between 1979 and 2012 in the Implant Prosthodontics Unit were contacted to solicit additional information about potential peri-operative use of NSAIDs. Results: From a total of 168 patients with 292 implant failures between 1979 and 2012, 122 consented to participate and had intact records. Just over half (56.6%) reported no peri-operative NSAID usage. However, compared to patients who did not use peri-operative NSAIDs, four times as many had complicated medical histories and twice as many patients taking NSAIDs suffered multiple implant failures. Conclusions: Patients with a variety of systemic diseases may be adversely affected by the inhibitory effect of NSAIDs on bone healing. Further prospective clinical studies are warranted to clarify this potential causative relationship in humans.

Objective: To appraise whether adverse events following oral implant placement may be associated with peri-operative use of non-steroidal anti-inflammatory drugs (NSAIDs). Methods: All patients with recorded implant failures between 1979 and 2012 in the Implant Prosthodontics Unit were contacted to solicit additional information about potential peri-operative use of NSAIDs. Results: From a total of 168 patients with 292 implant failures between 1979 and 2012, 122 consented to participate and had intact records. Just over half (56.6%) reported no peri-operative NSAID usage. However, compared to patients who did not use peri-operative NSAIDs, four times as many had complicated medical histories and twice as many patients taking NSAIDs suffered multiple implant failures. Conclusions: Patients with a variety of systemic diseases may be adversely affected by the inhibitory effect of NSAIDs on bone healing. Further prospective clinical studies are warranted to clarify this potential causative relationship in humans.

Absicht: Ziel dieser retrospektiven Arbeit war es den Erfolg des Behandlungskonzeptes der Sofortversorgung von oberen Frontzahnimplantaten unter Anwendung palatinaler kortikaler Satellitenimplantate zu überprüfen. Material und Methode: An der Befragung zur Erfassung der Überlebensrate und der Patientenzufriedenheit nahmen 44 Patienten teil (29 w, 15 m, Durchschnittsalter 58 Jahre), die in der oberen Frontzahnregion mit Implantaten unter Anwendung der palatinalen kortikalen Mikrofixation versorgt wurden. Eine klinische Untersuchung zur Erfassung des Knochenabbaus, der Periotestwerte, der Sondierungstiefen sowie des Papilla Presence Indizes erfolgte bei 35 der befragten Patienten. Ergebnisse: Die Gesamtüberlebensrate der Implantate betrug 98 % (mittlerer Beobachtungszeitraum 46 Monate). Ein mittlerer Knochenverlust von 0,87 mm und ein mittlerer Periotestwert von -0,02 konnten ermittelt werden. Mittlere Sondierungstiefen betrugen 1,72 bis 2,3 mm. Bei der Befragung der Patienten konnte eine hohe Patientenzufriedenheit mit dem Behandlungsergebnis der Implantation festgestellt werden. Fazit: Die Ergebnisse dieser Arbeit zeigen, dass das Konzept der implantologischen Sofortversorgung mit palatinaler subgingivaler kortikaler Mikrofixation in der oberen Frontzahnregion positive Ergebnisse liefert.

Thesis (Ph. D.)--Johann Wolfgang Goethe University, 2003. / Includes bibliographical references.

Thesis (Ph. D.)--Johann Wolfgang Goethe University, 2003. / Includes bibliographical references.