Orientador: Elcio Marcantonio Junior / Resumo: O objetivo do presente estudo foi investigar a ocorrência das doenças peri-implantares e a influência de possíveis fatores de risco utilizando duas abordagens metodológicas diferentes. Inicialmente realizou-se um estudo retrospectivo para avaliar a sobrevivência e o sucesso de implantes com superfície tratada com ataque ácido após 8 a 10 anos de função. Quarenta e quatro pacientes e 183 implantes foram incluídos. Dados demográficos, sistêmicos e comportamentais foram obtidos seguidos da avaliação clínica periodontal, peri-implantar e radiográfica realizados em uma única sessão. Nesse estudo relatou-se, nos 183 implantes avaliados, um índice de sobrevivência e sucesso de 97,3% e 84,7%, respectivamente. Dos implantes sobreviventes, 51% apresentavam mucosite e 11% peri-implantite. Posteriormente investigou-se, em um estudo prospectivo, a incidência de mucosite e perda óssea peri-implantar após 1 ano em função. Foram incluídos 56 pacientes totalizando 180 implantes. O exame clínico periodontal e peri-implantar seguido de radiografias periapicais padronizadas foi realizado 15 dias após a instalação das próteses e após 3, 6 e 12 meses de função. Com essa abordagem, observou-se uma incidência de 44,8% de mucosite peri-implantar, porém nenhum caso de peri-implantite foi observado nos 180 implantes avaliados. Implantes com conexão hexagono interno apresentaram incidência de mucosite significativamente maior após 1 ano de acompanhamento. Ademais, uma média de perda óssea peri-implantar... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The purpose of this investigation was to assess the incidence of peri-implant diseases and how they can be associated to possible risk factors. Two different approaches were addressed. Through a retrospective study, survival and success rates of implants with acid-etched-treated surface were initially evaluated in 44 patients, with 183 implants, in function for 8 to 10 years. Analysis included demographic, systemic and behavioral data, followed by one-session radiographic, periodontal and peri-implant clinical evaluations. This first study yielded survival and success rates of 97.3% and 84.7%, respectively, for the 183 investigated implants. Among the surviving implants, 51% were affected by mucosite and 11%, by peri-implantitis. A second study was also carried out to prospectively investigate mucosite incidence as well as peri-implantar bone loss in 180 implants, placed in 56 patients, after 1 year of function, which were assessed by clinical periodontal and peri-implant examinations, followed by standardized peri-apical radiographs, carried out 15 days after installation of the prosthesis, and at 3, 6 and 12 months of function. This observation revealed a 44.8% rate of peri-implant mucosite; however, no case of peri-implantitis was found. Implants with an intern-hexagon platform were significantly more affected by mucositis after one year of observation. In addition, a mean peri-implant bone-loss of 0.35 ± 1.89 mm was detected, however none of the patient or implant-related... (Complete abstract click electronic access below) / Doutor

Orientador: Elcio Marcantonio Junior / Resumo: O objetivo desse estudo foi de avaliar retrospectivamente a taxa de sobrevivência de implantes com diferentes tipos de conexão protética instalados na região posterior de maxila, em osso nativo ou em seios previamente enxertados com diferentes biomateriais. Foram avaliados 310 implantes que foram instalados em 103 pacientes sendo que 87 implantes foram instalados associados a seios maxilares enxertados (56 cone morse - CM e 31 hexágonos externos-HE) em 37 pacientes e 223 implantes foram instalados em áreas de osso nativo (112 CM e 111 HE) em 76 pacientes. Foram realizadas análises clínicas peri-implantares: 1)Sangramento à sondagem; 2)Profundidade de sondagem; 3)Nível da margem periimplantar; 4)Presença de mobilidade ou supuração e análise do nível ósseo radiográfico. Dois implantes foram perdidos, um CM em osso nativo e um HE em seio enxertado, o que forneceu uma taxa de sobrevivência de 99.35 %. Foi verificado que os implantes do tipo CM apresentaram menores profundidades de sondagem e maior nível ósseo periimplantar em comparação aos implantes HE tanto em área enxertada como em área de osso nativo (p<0.05). Não houve diferenças estatisticamente significativas entre os implantes instalados em áreas de osso nativo e enxertado em nenhum parâmetro avaliado. Implantes HE instalados em áreas de osso nativo apresentaram maiores taxas de peri-implantite. Pode-se concluir que implantes de plataforma do tipo CM reduzem a perda óssea periimplantar, porém a instalação de implantes em ... (Resumo completo, clicar acesso eletrônico abaixo) / Doutor

Orientador: Joni Augusto Cirelli / Resumo: A qualidade do tecido ósseo representa condição “sine qua non” para a estabilidade e longevidade de implantes biomédicos. Diante de fatores sistêmicos relacionados à insuficiência e/ou má qualidade do tecido ósseo peri-implantar, o desenvolvimento de superfícies de titânio com atividade osteogênica é amplamente incentivado na área da implantodontia. Sendo assim, este Estudo avaliou diferentes formas de tratamentos da superfície das amostras de titânio comercialmente puro (Ticp) e titânio liga 6Alumínio-4Vanádio, que visam o favorecimento dos mecanismos celulares de osteogênese. Este estudo foi divido em 2 capítulos. Na publicação 1 as amostras foram divididas em 3 grupos de acordo com os tratamentos (Grupo 1: Titânio comercialmente puro – MS; Grupo 2: Tratamento com NaOH - AES; Grupo 3: Tratamento com NaOH associado à deposição de Estrôncio (Sr) – Sr-AES. Os resultados demonstraram que as superfícies dos Grupos 2 e 3 apresentaram-se mais rugosas, quando avaliadas em perfilômetro, e mais hidrofílicas em teste de molhabilidade, em comparação às do Grupo 1 (p < 0.05, One Way Anova). As células em contato com a superfície do Grupo 3 apresentaram espraiamento celular mais evidente, em comparação aos Grupos 1 e 2, indicando que a adição do estrôncio às amostras foi favorável ao desenvolvimento das células precursoras ósseas. Na publicação, as amostras foram divididas em 3 grupos de acordo com os diferentes tratamentos. Grupo A: titânio comercialmente puro – Ticp; Grupo B: Ti-6Al-4V... (Resumo completo, clicar acesso eletrônico abaixo) / Doutor

Introduction: Gram-negative prosthetic joint infections (GN-PJI) present unique challenges in management due to their distinct pathogenesis of biofilm formation on implant surfaces. The purpose of this study is to establish a clinically representative GN-PJI model that can reliably recapitulate biofilm formation on titanium implant surface in vivo. I hypothesized that biofilm formation on an implant surface will affect its ability to osseointegrate. Methods: The model was developed using 3D-printed titanium hip implants, to replace the femoral head of male Sprague-Dawley rats using a posterior surgical approach. GN-PJI was induced using two bioluminescent Pseudomonas aeruginosa (PA) strains: a reference strain (PA14-lux) and a mutant strain that is defective in biofilm formation (flgK-lux). Infection was assessed in real-time using the in vivo imaging system (IVIS) and Magnetic Resonance Imaging (MRI) and in vitro by quantifying bacterial loads on collected implants surface and in periprosthetic tissues as well as biofilm visualization using the Field emission scanning electron microscopy (FE-SEM). The implant stability, as an outcome, was directly assessed by quantifying the osseointegration in vitro using microCT scan, and indirectly assessed by identifying the gait pattern changes using DigiGaitTM system in vivo. Results: Bioluminescence detected by IVIS, was focused on the hip region, demonstrating localized-infection, with the ability of PA14-lux to persist in the model compared to flgK-lux defective in biofilm formation. This was corroborated by MRI as the PA14-lux induced relatively larger implant-related abscesses. Biofilm formation at the bone-implant-interface induced by the PA14-lux was visualized using FE-SEM versus defective-biofilm formation by flgK-lux. This could be quantitatively confirmed, by average viable-colony-count of the sonicated implants, 3.77x108CFU/ml versus 3.65x103CFU/ml for PA14-lux and flgK-lux, respectively (p=0.0025; 95%CI: -6.08x108 to -1.45x108). This difference in the ability to persist in the model was reflected significantly on the implant osseointegration with a mean intersection surface 4.1x106μm2 1.99x106 for PA14-lux versus 6.44x106μm2 2.53x106 for flgK-lux and 7.08x106μm2 1.55x106 for non-infected control (p=0.048). Conclusions: To date, the proposed in vivo biofilm-based model is the most clinically representative for GN-PJI since animals can bear weight on the implant and poor osseointegration correlates with biofilm formation. Clinical Relevance: The current model will allow for reliable testing of novel biofilm-targeting therapeutics.

Zirconia has been established as a promising material for dental implants. Various surface treatment methods have been utilized to promote better osseointegration and improve the success rate of dental implants. However, a better understanding of the influences of topographic characteristics on cell attachment, proliferation, and differentiation is needed. Different surface topographic zirconia specimens, As sintered, Mild rough, Moderate rough, and Rough zirconia groups were fabricated with sandblasting method in various distances and stages. The surface texture, microstructure, and wettability were inspected with the optical profiler, SEM, and contact angle measurement respectfully. Human primary osteoblast cells were cultured on the four groups of zirconia with different surface modifications in 24 well plates and on plates without test material as control. Crystal violet and triton X-100 solution were used to evaluate cell attachment efficiency at 9 hours and proliferation rate at 7, 14, and 21 days after seeding. ALP activity was measured with fluorometric assay. The expression of osteocalcin was measured with an ELISA kit. Alizarin red staining was conducted to evaluate the mineralization. The cell morphologies were inspected under SEM after cell fixation and critical point drying process. The data were analyzed with one-way ANOVA for experiment on each time interval and two-way ANOVA for all time points. Tukey post hoc test was used for pairwise comparison. P value < 0.05 was considered statistically significant. Topographic parameters and contact angle measured in As sintered, Mild rough, Moderate rough, and Rough surface groups were as follow: Sa = 0.23, 0.50, 2.13, 5 µm, Sal = 49.88, 21.20, 30.42, 49.87 µm, Sdq = 64.64, 248.60, 511, 734.66 µm/mm, Sk = 0.7, 1.54, 4.19,16 µm, Spk = 0.31, 0.64, 1.47, 5.13 µm, Svk = 0.35, 0.71, 5.96, 6.18 µm respectively, and contact angle = 64.6°, 55.2°, 43.5°, 38.6° respectively. The result showed that Rough zirconia group induced the highest cell attachment efficiency at 9 hours (p<.001). As sintered zirconia group promoted significant cell proliferation rate at 21 days (p<.001) while Rough zirconia group drastically down-regulated cell proliferation (p<0.001). The most elevated levels of ALP, osteocalcin, and mineralization expressions at 21 days were found in the Moderate rough group with significant differences (p<.001, p<.001, p<.001 accordingly) Within the limitations of this in vitro study, it can be concluded 1) the modified microroughened zirconia surfaces of Sa 5 µm would promote human osteoblast attachment but down-regulate cell proliferation, 2) the As sintered zirconia surface would stimulate cell proliferation, and 3) the microroughened surfaces of Sa 2 µm would up-regulate osteoblast differentiation. These findings could be incorporated into designing and fabricating the dental implant surfaces for optimal osseointegration.

Medical implants constitute an essential advancement in modern medicine, often restoring or replacing functionality to failed organs. Whether a medical implant is temporary or permanent, medical implants carry the risk of implant failure due to an infection. Implant-associated infections (IAI) are challenging to treat and often result in increased medical costs, prolonged hospital stays, implant failure, and, in some instances, severe infections that can lead to amputations, sepsis, or mortality. Eradicating an IAI can be challenging since bacteria can form biofilms on the implant’s surface. The biofilms comprise an extracellular matrix protecting the bacterial cells against systemic antibiotics and the host’s immune system. Treating an IAI usually entails a broad range of antibiotic treatment and surgical procedures for tissue debridement or implant replacement. For the reasons stated above, scientists and engineers continue to develop technologies to protect the surface of medical implants against infections. Amongst the new technologies, Liquid-Infused Surfaces (LIS) are renowned for their repellent and anti-fouling properties created by tethering a stable liquid layer onto the surface. However, many challenges remain to adopt this technology for implantable devices. For instance, the high repellent properties can hinder implant-tissue interaction and discourage proper integration with the body. Furthermore, the stable liquid layer is contingent on the surface properties of the coated material. In other words, the long-term stability of these coatings may be compromised if the surface chemistry is covered by biological processes such as biofilm formation from adherent bacteria. This thesis aims to expand on the applications of LIS coatings and enhance their properties for implantable materials. This thesis reviews different types of antibiotic surface coatings and further examines LIS technologies as a viable antibacterial coating for medical implants. Then, three novel multifunctional LIS coatings are presented. The first developed coating enhanced the antibacterial properties of the coating by adding bactericidal agents within the LIS coating. The developed antibiotic liquid-infused coating not only repelled bacteria but also lysed bacteria upon contact. The second coating was designed to promote tissue integration. This multifunctional coating promoted cell deposition and proliferation while remaining repellent toward bacteria, while the conventional LIS coating displayed poor cell availability. Lastly, a collagen-bacteriophage conjugated liquid-infused coating was developed to promote tissue integration while having a two-tier layer of antibacterial protection. This coating was tested in a mouse sepsis model and prevented mortality of all mice, with other groups as high as 90% mortality. These coatings constitute essential steppingstones to bring LIS technology to medical implants. / Dissertation / Doctor of Philosophy (PhD) / Implant-associated infections (IAI) remain a significant problem in modern medicine. IAIs are challenging to treat and often result in increased medical costs, prolonged hospital stays, implant failure, and, in some instances, severe infections that can lead to sepsis or mortality. For these reasons, new technologies have been developed to protect the surface of medical implants against infections. Amongst the new technologies, Liquid-Infused Surfaces (LIS) are renowned for their repellent and anti-fouling properties created by tethering a stable liquid layer onto the surface. This thesis aims to expand on the applications of LIS coatings and enhance their properties for implantable materials. This thesis reviews different types of antibiotic surface coatings, examines LIS technologies, and presents three novel multifunctional LIS coatings. The newly developed coatings enhance the LIS coatings through the addition of antibacterial properties and biomolecules to promote tissue integration.

No description available.

Bone implants procedures involve millions of people every year worldwide. One of the main factors determining implant success is related to the ability of the prostheses to osseointegrate, i.e. to create a structural and functional connection with the living bone. Titanium and titanium alloys are widely used biomaterials for bone implants, due to their superior biocompatibility and corrosion resistance, suitable mechanical properties, and natural ability to osseointegrate. To further enhance the inherent tendency of this class of materials to bond with the host bone tissue, the surface of Ti-based implant is often modified to improve cell responses in terms of adhesion, proliferation and differentiation, all factors contributing to successful osseointegration. In particular, surface topography, both at the micro- and nanoscale, can enhance the implant-living bone interaction. Herein, a possible surface modification strategy aimed at the creation of a dual-scale topography on two different titanium alloys, Ti-6Al-4V and Ti-5Al-5Mo-5V-3Cr, is presented. Dual-scale topography was obtained by electrochemically anodizing samples manufactured by selective laser melting to combine their intrinsic microtopography with the nanotopography offered by titanium dioxide nanotubes (TNTs) generated by anodization. Characterization of the as-printed and as-anodized samples was performed to evaluate parameters of significance in the context of osseointegration. Concerning wettability, it was observed that surfaces with TNTs exhibited high hydrophilicity. The influence of the anodization process parameters on TNTs morphology was examined, and linear dependence of the nanotube diameter on the voltage was identified. Annealing of the as-anodized samples showed that anatase was produced, while preserving the nanotube integrity. Preliminary studies to assess the bioactive properties of the samples showed the spreading of bone-like cells on these substrates and the deposition of mineral during simulated body fluid testing. Therefore, both studies provided promising results to corroborate the hypothesis that dual-scale topography could potentially improve osseointegration. / Thesis / Master of Applied Science (MASc) / Bone implants are often made of titanium-based materials, which, despite their suitable properties, may not sufficiently bond with the living bone tissue. This can lead to implant loosening and failure. To produce customized implants, additive manufacturing, or 3D-printing, can be employed. However, these surfaces require substantial post-processing to produce features capable of promoting bone integration. In this work, a dual-scale surface topography to combine the advantages of both micro- and nanoscale roughness was created using electrochemical anodization on 3D-printed titanium alloy substrates. Preliminary physical, chemical, and biological characterizations suggest that the creation of titania nanotubes on the 3D-printed surfaces of Ti-6Al-4V and Ti-5Al-5Mo-5V-3Cr could improve their ability to bond with bone.

Das Ziel dieser Arbeit war es, das klinische Resultat der implantatverankerten Ohrepithese retrospektiv zu untersuchen. Es wurden die Daten von 46 Patienten erhoben, die von 1992 bis 2003 mit implantatverankerten Ohrepithesen versorgt wurden. Bei 20 Patienten mit 53 Implantaten wurde eine spezielle Nachuntersuchung zur Beurteilung der periimplantären Weichgewebssituation durchgeführt. Zwei objektive klinische Parameter, die Sondierungstiefe und die Sulcus Fluid Flow Rate (SFFR), wurden hierfür angewendet. Die subjektive Beurteilung der Hautreaktionen war durch das Graduierungsystem von Holgers klassifiziert. 24 Patienten wurden mit Hilfe eines einheitlichen Fragebogens über die Zufriedenheit und auf mögliche Beschwerden befragt. Die kongenitalen Ohrmissbildungen (62,5%) waren die häufigsten Indikationen bei dieser Behandlung. 156 Implantate und eine Trägerplatte (Epitec-System®) bei den 46 Patienten inseriert, darunter waren 23 Implantate aus dem EO-System®, sowie 133 aus dem Brånemark-System®. Intraoperative Komplikationen traten bei der Implantatinsertion nicht auf. Die Implantationserfolgsrate liegt bei 100%. Bei 34 Patienten (74%) wurden insgesamt 42-mal Hautreaktionen (Entzündungen, Blutungen, Schwellungen) während der Nachkontrolle registriert. Die durchschnittliche Tragezeit der Ohrepithesen betrug 2,7 Jahre. Periimplantäre Hauttaschen sind in unserer Studie bei allen untersuchten Implantaten beobachtet worden. In der speziellen Nachuntersuchung lag der mittlere Wert der Sondierungstiefe und der SFFR bei 2,1 mm bzw. 1,8 mm. Zwischen beiden Parameter wurde eine starke Korrelation festgestellt: Je tiefer die Sondierungstiefe desto höher waren die Werte der SFFR. Bei 22 Implantaten (41,5%) ergaben sich keine Hautreaktionen. Die Entzündungen wurden nur an vier Implantaten (7,5%) beobachtet. 91,7% der befragten Patienten waren mit ihrer Ohrepithese zufrieden. Anhand unserer Studie, dass die implantatverankerten Ohrepithese heute ausgezeichnete und stabile Langzeitergebnisse erzielt werden können. Die tiefe Hauttasche spricht für ein Zeichen der periimplantären Entzündung und eine Notwendigkeit einer periimplantäreren Hautausdünnung. / The purpose of this study is to retrospectively evaluate the clinical results of the implant-retained auricular prosthesis. The data of 46 patients who were treated between 1992 and 2003 with implant-retained auricular prosthesis were evaluated. 20 patients with 53 implants were re-examined to evaluate the periimplant soft tissue situation with two objective clinical parameters periimplant sulcus probing depth and sulcus-fluid-flow-rate (SFFR). The subjective evalution of skin reactions around the abutments was classified as reported by Holgers. Satisfaction and eventual complications were evaluated in 24 patients by using standardized Questionnaires. Congenital malformation (62.5%) was the most common indications for auricular prostheses. A total of 156 implants and a plate (Epitec-System®) were placed in 46 patients, 23 of which were EO-System®, and 133 were Brånemark-System®. No intraoperative complications were reported during the insertion of implants. The implant survival rate was 100%. 42 times of skin reactions (inflammation, bleeding, swelling) were registered in 34 patients. The average wearing time of the prosthesis was 2.7 year. Skin pockets were found in all of the 53 re-examined implants. The middle value of sulcus probing depth and SFFR was respectively 2.1 mm and 1.8 mm. A strong correlation was found between the two parameter, which suggests that a deeper sulcus always presents a high value of SFFR. No adverse skin reactions was found in 22 implants (41.5%). Severe inflammation was observed in only 4 implants (7.5%). 91,7% of patients were satisfied with their prostheses. From this study it can be concluded that the implant-retained auricular prostheses offer a good and secure perspective for patients. The deep sulcus shows a sign of periimplantitis and a surgical thinning of subcutaneous periimplant soft tissue should be perfomed to eliminate it.

Cell adhesion to the extracellular matrix through cell-surface integrin receptors is essential to development, wound healing, and tissue remodeling and therefore represents a central theme in the design of bioactive surfaces that successfully interface with the body. This is especially significant in the areas of integrative implant coatings since adhesion triggers signals that regulate cell cycle progression and differentiation in multiple cellular systems. The interactions of osteoblasts with their surrounding extracellular matrix are essential for skeletal development and homeostasis and the maintenance of the mature osteoblastic phenotype. Our objective was to engineer integrin-specific bioactive surfaces that support osteoblastic differentiation and promote osseointegration by mimicking these interactions. We target two specific integrins essential to osteoblast differentiation the type I collagen receptor alpha2beta1 and the fibronectin receptor alpha5beta1. The central hypothesis of this project was that the controlled presentation of type I collagen and fibronectin binding domains onto well-defined substrates would result in integrin-specific bioadhesive surfaces that support osteoblastic differentiation, matrix mineralization, and osseointegration. We have demonstrated that these biomimetic peptides enhance bone formation and mechanical osseointegration on titanium implants in a rat tibia cortical bone model. We have also shown that the presentation of multiple integrin-binding ligands synergize to enhance intracellular signaling and proliferation. Finally, we demonstrate the advantage of the short biomimetic peptides over the native ECM proteins. This research is significant because it addresses current orthopaedic implant limitations by specifically targeting cellular responses that are critical to osteoblastic differentiation and bone formation. This biomolecular approach provides a versatile and robust strategy for developing bioactive surfaces that enhance bone repair and osseointegration of orthopaedic implants.