Diseases involving fibrosis cause tens of thousands of deaths per year in the US alone. These diseases are characterized by a large amount of extracellular matrix, causing stiff abnormal tissues that may not function correctly. To take steps towards curing these diseases, a fundamental understanding of how cells interact with their substrate and how mechanical forces alter signaling pathways is vital. Studying the mechanobiology of cells and the interaction between a cell and its extracellular matrix can help explain the mechanisms behind stem cell differentiation, cell migration, and metastasis. Due to the correlation between force, extracellular matrix assembly, and substrate stiffness, it is vital to make in vitro models that more accurately simulate biological stiffness as well as measure the amount of force and extracellular matrix assembly. To accomplish this, blends of two types of poly(dimethylsiloxane) (PDMS) were made and the material properties of these polymer blends were characterized. A field of 5µm or 7µm microscopic pillars (referred to as posts) with a diameter of 2.2µm were fabricated from these blends. Each combination of PDMS blend and post height were calibrated and the stiffness was recorded. Additionally, polymer attachment experiments were run to ensure cells survived and had a normal phenotype on the different blends of PDMS when compared to pure PDMS. Finally, cells were placed onto a field of posts and their forces were calculated using the new stiffness found for each blend of post. Varying the PDMS material stiffness using blends allow posts to be much more physiologically relevant and help to create more accurate in vitro models while still allowing easy and accurate force measurement. More biologically relevant in vitro models can help us acquire more accurate results when testing new drugs or examining new signaling pathways.

Les lésions de cartilage ne cicatrisent pas spontanément et la réparation de ce tissu est un challenge. Les techniques chirurgicales restant insatisfaisantes, la thérapie cellulaire et l'ingénierie tissulaire sont maintenant envisagées. La transplantation de chondrocytes autologues (TCA) existe déjà mais cette procédure nécessite l'amplification des chondrocytes qui s'accompagne d'une perte du phénotype différencié (dont l'indicateur est le collagène de type II), au profit d'un phénotype fibroblastique (dont l'indicateur est le collagène de type I, retrouvé dans les tissus fibreux). La TCA conduit donc à une greffe de chondrocytes dédifférenciés produisant un fibrocartilage, dont les propriétés mécaniques sont différentes du cartilage hyalin natif. L'objectif de mes travaux était de développer un nouveau kit d'ingénierie tissulaire du cartilage par association de chondrocytes humains, de biomatériaux et d'une sélection de facteurs solubles. Nous avons utilisé le cocktail FGF-2/insuline (FI) pour l'amplification cellulaire et le cocktail BMP-2/insuline/T3 (BIT) pour redifférencier les chondrocytes dans des éponges de collagène. Nos résultats ont montré que cette combinaison permet la synthèse d'une matrice cartilagineuse dans les supports collagène. Cependant, cette synthèse s'est trouvée favorisée en périphérie des éponges cultivées en conditions statiques. Nous avons ensuite utilisé un bioréacteur pour perfuser les éponges et nos résultats ont révélé alors un dépôt plus homogène de cartilage dans ces supports. De manière très intéressante, nous avons aussi observé l'arrêt de l'expression du collagène de type I. Ainsi, notre approche multifactorielle combinant des chondrocytes humains, des biomatériaux collagène, une combinaison FI-BIT et une culture en perfusion permet la reconstruction d'un cartilage non fibrotique / Cartilage lesions are irreversible and cartilage repair is challenging. Actual surgical techniques remain unsatisfactory and therefore, cell therapy and tissue engineering approaches are now considered. The Autologous Chondrocytes Transplantation (ACT) already exists but this procedure requires chondrocytes amplification. During this amplification, a dedifferentiation process occurs: chondrocytes lose their differentiated phenotype (characterized by type II collagen) towards a fibroblastic phenotype (characterized by type I collagen, a component of fibrous tissues). ACT leads to the graft of dedifferentiated chondrocytes, hence provoking the production of a fibrocartilage that presents different mechanical properties than native hyaline cartilage. The aim of my work was to develop a new kit of tissue engineering for cartilage repair using human chondrocytes, biomaterials and a selection of soluble factors. We used a cocktail of FGF-2 and insulin (FI) for cell amplification and a cocktail of BMP-2, insulin and T3 (BIT) for chondrocyte redifferentiation in collagen sponges. Our results showed that the combination allows the synthesis of a cartilaginous matrix in collagen scaffolds. However, matrix production is favored in periphery of the sponges cultivated in static conditions. A perfusion bioreactor was then used to perfuse the sponges and our results revealed a more homogeneous deposition of cartilage in the scaffolds. Very interestingly, we also noticed a stop of type I collagen expression. Thus, our multifactorial approach combining human chondrocytes, collagen scaffold, the combination FI-BIT and culture under perfusion allows the reconstruction of a non-fibrotic cartilage

<div>Pancreatic cancer is the present third leading cause of all cancer-associated deaths with a under 9% 5-year survival rate. Aggressive tumor progression and lack of early detection technique lead to the fact that most patients are diagnosed at terminal stage - pancreatic ductal adenocarcinoma (PDAC). Despite that numerous therapeutic approaches have been introduced, most options cannot advance to or fail at the clinical trials. It has been suggested that previous failure is due to insufficient understanding of PDAC tumor microenvironment (TME). Human PDAC is composed of severely fibrotic tissue (i.e., desmoplasia) that harbors a variety of malignant cells (e.g., pancreatic stellate cells, cancer-associated fibroblasts, macrophages, etc.), excessive extracellular matrices (ECM), as well as abnormal expression of growth factors, cytokines, and chemokines. Multiple cell-cell and cell-ECM interactions jointly result in a stiffened, hypoxic, and fluid pressure-elevated PDAC tissue. The resulting pancreatic TME not only physically hinders penetration of therapeutics, but also dynamically interacts with the residing cells, regulating their behaviors.</div><div><br></div><div>Increasing tumor tissue stiffness in PDAC is not only a passive outcome from desmoplasia, but an active environmental factor that promotes tumor survival, growth, and invasion. However, traditional in vitro cell culture systems such as two-dimensional (2D) culture plate and animal models are not ideal for mechanistic understanding of specific cell-matrix interactions. Therefore, dynamic hydrogels have been introduced as a category of advanced biomaterials that exhibit biomimetic, adaptable, and modularly tunable physiochemical property. Dynamic hydrogels can be precisely engineered to recapitulate a variety of aspects in TME, from which to investigate the role of dynamic tumor-stroma interaction in PDAC progression. The goal of this dissertation was to exploit synthetic polymers (i.e., poly(ethylene glycol) (PEG)) or natural ECM (i.e., gelatin and hyaluronic acid (HA)) as precursors to prepare the dynamic cancer-cell laden gels. The design utilized the orthogonal thiol-norbornene photopolymerization to prepare the primary homogenous xxvi</div><div><br></div><div>gel network. Next, through further functionalizing gel precursors with phenolic derivatives, enzymatic reaction (i.e., tyrosinase) or flavin mononucleotide (FMN)-mediated photochemistry could be harnessed to manipulate the dynamic changes of substrate mechanics. Experimentally, a computational model and the associated validation were presented to investigate the process of gel stiffening. Finally, these techniques were integrated to prepare cell-laden gels with spatial-temporally tunable properties that were instrumental in exploring the synergistic effects of dynamical matrix stiffening and presence of HA in promoting epithelial-mesenchymal transition (EMT) in PDAC cancer and stromal cells.</div>

<p>Bioresorbable iron-manganese (Fe-Mn) alloys are considered as a new class of biomaterials for the development of orthopedic fixation devices due to their promising mechanical properties, comparable to the human cortical bone, and the ability to degrade in the physiological environment and release small quantities of metallic ions/particles that are absorbable by the host. The greatest challenge for developing an ideal resorbable Fe-Mn alloy is to increase the degradation rate of the alloy without compromising the alloy biocompatibility, that is, causing zero or minimal local and systemic toxicity to the tissue. Another challenge is to improve osteo-integration through inducing a cascade of events leading to tissue ingrowth.</p> <p> </p> <p>The incorporation of porosity into the Fe-Mn alloys aimed to increase the corrosion rate and to provide the three-dimensional structure for cellular activity and nutrient transport. The Fe-30wt.%Mn alloys with 0-, 5-, 10-, and 60-volume percent porosity were produced through the space holder technique in powder metallurgy. The space-holder material, ammonium bicarbonate (NH₄HCO₃), was sieved to a particle size ranging 355~500 µm. The microstructures and mechanical properties of the alloys, as well as the influence of the degree of porosity on the alloy corrosion rates comparing to the concentrations of the degraded metal ions were investigated. Although the Fe-30Mn alloys containing 60-vol% porosity exhibited the lowest average ultimate compressive strength of 381 MPa among the tested groups, they were still mechanically stronger than a typical human wet compact bone. Furthermore, the alloys had the highest average corrosion rate of 0.98 ± 0.20 mm/year, compared to 0.13 ± 0.07 mm/year for the non-porous Fe-30Mn alloys. Nevertheless, the extract from the 60%-pore group had a cytotoxicity effect to the bone marrow stem cells (BMSCs) at an average normalized cell viability of 58%, which was below the standard viability of 70%, considered as cytotoxic in the indirect cytotoxicity study. The cytotoxicity study also corresponded to the highest level of transition metal ions Mn²⁺ released into the media for the 60%-pore group at an average ion released rate of 7 mg/day, compared to the other groups presenting similar Mn²⁺ released rates about 4 mg/day after 1 day of incubation. The extreme case of the 60%-pore group demonstrated the tradeoff between the corrosion rates and biocompatibility. On the other hand, the 10%-pore group showed an average ultimate compressive strength of 737 MPa comparable to the stainless steel 316L, an average corrosion rate of 0.260 ± 0.09 mm/year, which was 2-fold higher than the non-porous group, and an average cell viability of 86% close to the non-porous group. It is promising based on the above results, however, the osteo-integration of the 10%-pore group in terms of cell-to-cell and alloy-to-cell interactions was not ideal. </p>

Les Interfaces Cerveau-Machine assurent une connexion bidirectionnelle entre un patient et son environnement. Un patient atteint de déficience motrice lourde peut, au moyen d'un dispositif implanté dans son cerveau, commander des objets connectés par la seule action de son activité cérébrale. Une des premières exigences que cela requiert est de concevoir un implant, dit neuroprothèse, susceptible de rester implanté de façon chronique. L’utilisation des micro-nano-technologies permet de fabriquer une neuroprothèse qui réponde aux exigences d’un tel dispositif : performant, fiable et limitant la réaction de rejet par l’organisme. Pour cela, l’implant est conçu sur un substrat flexible à base de polymère biocompatible. La souplesse de l’implant lui permet de mieux s’adapter aux tissus cérébraux et d’assurer un contact intime avec les neurones en diminuant la réaction inflammatoire. Cet implant est inséré au moyen d’un support rigide biodégradable issu de la fibroïne de soie. Des premiers tests sur culture in vitro et sur petit animal (souris) ont montré des résultats prometteurs en termes de biocompatibilité et biostabilité sur le court et moyen terme. / Brain-Computer Interfaces ensure a bidirectional connection between a patient and his environment. Using an implant in his brain, a patient suffering from severe motor deficiency can control external devices through the sole action of his cerebral activity. One of the major requirements for such application is to conceive an implant, also called neuroprosthesis, that is able to be implanted for long periods of time.Micro-nano-technology enable the fabrication of a neuroprosthesis that gives in the demands of such item: efficient, reliable and limiting body rejection mechanisms. To that aim, the implant is designed on a flexible substrate provided by a biocompatible polymer. Implant flexibility allows for better compliance with the brain tissues and insures a more intimate contact with the neurons while maintaining minimal inflammation. This implant is inserted in the brain using a bioresorbable support made of silk fibroin. First tests in vitro on culture cells, and in vivo on mice showed promising results in terms of biocompatibility and biostability in the short and medium term.

Retalho posicionado coronalmente associado ao enxerto de tecido conjuntivo subepitelial (ETCS) é o padrão ouro para o tratamento de retrações gengivais. A matriz de colágena suína bioabsorvível Mucoderm® (MD) tem sido amplamente utilizada como substituto do ETCS e tem alcançado resultados semelhantes. o MD tem a vantagem de disponibilidade que supera as limitações do sítio doador em enxertos autógenos. O objetivo deste estudo é investigar o uso do MD nos procedimentos de recobrimento radicular combinado com retalho extendido posicionado coronalmente (REPC), grupo teste (GT), em comparação ao ETCS associado ao REPC, grupo controle (GC). Dezoito pacientes adultos, apresentando recessão tipo 1 bilateral foram selecionados. Parâmetros clínicos, profundidade de sondagem, nível clínico de inserção, altura (RG) e largura (LRG) da retração, altura (GQ) e espessura (EGQ) da gengiva queratinizada e área da retração (ARG) foram registrados no início, 3 e 6 meses após os procedimentos cirúrgicos por um examinador cego. Aos 6 meses, um periodontista realizou uma Escala Estética de Recobrimento Radicular (ERR) (Cairo et al. 2009) analisando a posição da margem gengival (MG), contorno do tecido marginal (CTM), textura do tecido mole (TTM), alinhamento da junção mucogengival (AJG) e coloração da gengiva (CG). Aos 3 e 6 meses, um questionário estético funcional para o paciente foi utilizado para avaliar a satisfação com a taxa de recobrimento (STR), coloração da gengiva (CG) e sensibilidade dentinária (SEN), esta última aplicada também no baseline, e se necessário, voltaria a realizar a cirurgia (CIR) em outras áreas. O paciente respondeu ao questionário em uma escala VAS. O GT e o GC apresentaram redução significativa na média da RG (3,33 ± 0,89mm a 1,31 ± 1,03mm (p &lt0,05) e 3,21 ± 0,80mm a 0,83 ± 0,86mm ( p &lt0,05)), LRG (4,03 ± 0,57mm a 2,73 ± 1,62mm 12 e 4,10 ± 0,63mm a 2,07 ± 1,79mm (p &lt0,05)) e ARG (222638 ± 99731pix&sup2 para 72727 ± 82631pix&sup2 e 196461 ± 84815pix&sup2 para 48414 ± 63398pix&sup2 (p &lt0,05)) respectivamente e ganho de GQ (1,87 ± 1,17mm para 2,85 ± 1,43mm (p &lt0,05) e 1,91 ± 0 , 95mm a 2,83 ± 1,41mm (p &lt0,05)) e EGQ (0,76 ± 0,21mm a 1,10 ± 0,31mm (p &lt0,05) e 0,86 ± 0,39mm a 1, 36 ± 0,40mm (p &lt0,05)) respectivamente em um período de 6 meses. A quantidade média de cobertura radicular não foi diferente entre GT (61,33%) e GC (73,90%) (p&gt 0,05). Não houve diferença entre o GC e o GT nos parâmetros analisados no ERR aos 6 meses e para o questionário estético funcional ao paciente houve redução significativa no parâmetro SEN no GT (54,55 ± 32,60% para 19,11 ± 25,73% (p &lt0,05)) e GC (55,61 ± 30,88% a 11,17 ± 17,51% (p &lt0,05)). Ambos os grupos mostraram uma redução significativa na RG. Considerando-se que não foram observadas diferenças significativas entre o GC e o GT para RG, LRG, ARG e GQ e EGQ foram significativamente diferentes favorecendo GT, pode-se especular que o MD possa ser usado como alternativa ao CTG para o tratamento de recessões gengivais / Coronally advanced flap plus connective tissue graft (CTG) is the gold standard therapy for root coverage. The bioabsorbable porcine collagen matrix Mucoderm® (MD) has been widely used in periodontal and mucogingival surgery as a substitute for CTG and has achieved similar results. The MD has the advantage of availability overcoming the limitations of donor site in autograft. The aim of this study is to investigate the use of MD in root coverage procedures combined with extended coronally positioned flap (ECAF), test group (TG) in comparison to the CTG associated with the ECAF, control group (CG). Eighteen adult patients, non-smokers, presenting bilateral Cairo´s Recession Type 1 (RT1) were selected. Clinical parameters, probing depth, clinical attachment level, recession height (RH) and width (RW), keratinized tissue height (KTH) and thickness (KTT) and gingival recession área (GRA) were recorded at baseline,3 and 6 months after the surgical procedures by a blinded examiner. At 6 months a specialist in periodontics performed a Root Coverage Esthetic Score (RES) (Cairo et al. 2009) analyzing position of the gingival margin (GM), marginal tissue contour (MTC), soft tissue texture (STT), mucogingival junction alignment (MJA) and gingival color (GI). At 3 and 6 months a functional aesthetic questionnaire to the patient was used to evaluate the satisfaction with recovering rate (SRR), gingival color (GI) and dentin sensitivity (SEN) (the latter applied initially in the baseline) and, if necessary, would return to perform the surgery (SUR) in other areas. The patient answered the questionnaire on a VAS scale.The TG and CG showed a significant reduction in average for RH (3.33 ± 0.89mm to 1.31±1.03mm (p&lt0.05) and 3.21±0.80mm to 0.83±0.86mm (p&lt0.05)), RW (4.03±0.57mm to 2.73±1.62mm and4.10±0.63mm to 2.07±1.79mm (p&lt0.05)) and GRA (222638±99731pix&sup2 to 72727±82631pix&sup2 and 196461±84815pix&sup2 to 48414±63398pix&sup2 (p&lt0.05)) respectively and gain of KTH (1.87±1.17mm to 2.85±1.43mm (p&lt0.05) and 1.91±0.95mm to 2.83±1.41mm (p&lt0.05)) and KTT 14 (0.76±0.21mm to 1.10±0.31mm (p&lt0.05) and 0.86±0.39mm to 1.36±0.40mm (p&lt0.05)) respectively in a period of 6 month. The average amount of root coverage was not different between TG (61.33%) and CG (73.90%) (p&gt0.05). There was no differences between CG and TG on the parameters analyzed in the RES on 6 months and for the functional aesthetic questionnaire to the patient significant reduction was found on SEN parameter on TG (54.55±32,60% to 19.11±25.73% (p&lt0.05)) and CG (55.61±30.88% to 11.17±17.51% (p&lt 0.05)).In these 6 months follow up study, both groups showed a significant reduction in recession height. Considering no significant differences were observed between CG and TG for RH, RW, GRA and KTH and KTT were significant different favoring TG, it can be speculated that MD can be used as an alternative to CTG for the treatment of gingival recessions

Os aços inoxidáveis ferríticos são naturalmente ferromagnéticos, o que impossibilita sua utilização em próteses ortopédicas. Apesar disso, em algumas aplicações específicas, faz-se necessário o uso de um biomaterial ferromagnético, como nas próteses odontológicas e faciais com conectores magnéticos. Este trabalho apresenta o estudo da resistência à corrosão e citotoxicidade do aço inoxidável ferrítico AISI 444, para avaliar seu potencial de uso como um biomaterial. O aço AISI 444 possui baixo teor de níquel, teores extrabaixos de intersticiais (C e N) e é estabilizado com Ti e Nb. Como materiais de referência foram utilizados o aço inoxidável austenítico ISO 5832-1 (ASTM F-138), por ser o biomaterial metálico mais empregado na fabricação de próteses ortopédicas, e uma base ferromagnética do sistema de fixação de próteses odontológicas, feita em aço inoxidável ferrítico (NeoM). O ensaio de citotoxicidade in vitro, pelo método de incorporação do corante vermelho neutro, revelou que o aço inoxidável AISI 444 não apresentou citotoxicidade. O comportamento frente à corrosão foi estudado por meio de curvas de polarização anódica potenciodinâmicas e espectroscopia de impedância eletroquímica (EIE). O meio de ensaio foi uma solução salina tamponada de fosfato (PBS), em condição naturalmente aerada e em fresta, a temperatura de 37 ºC. Para simular a condição de fresta dos ensaios eletroquímicos foi desenvolvido um novo equipamento. As propriedades eletrônicas do filme passivo foram avaliadas pela técnica de Mott-Schottky. Em meio aerado, os resultados de EIE indicaram que todos os materiais se mostraram passivos. As curvas de polarização indicaram que a resistência à corrosão por pite do aço AISI 444 foi equivalente à do aço ISO 5832-1, porém superior à do NeoM. Pelos diagramas de Mott-Schottky, conclui-se que o filme óxido no aço AISI 444 possui menor concentração de dopantes que o aço NeoM. Isto sugere que o aço AISI 444 apresenta maior resistência à transferência de carga através do filme passivo. Em condição de fresta, as polarizações indicaram taxas de corrosão baixas para ambos os aços, porém superiores para o aço ISO 5832-1, em comparação ao aço AISI 444. As micrografias das superfícies dos aços, após polarização, revelaram um maior ataque corrosivo no aço ISO 5832-1 do que no aço AISI 444. O aço NeoM apresentou composição química fora da especificação da norma. Os baixos teores de Cr e de Mo, além das altas concentrações de sulfetos, foram as prováveis causas da menor resistência à corrosão do NeoM, indicada pelos ensaios eletroquímicos. O equipamento proposto para avaliação da resistência à corrosão, em condição de fresta, mostrou boa reprodutibilidade de resultados. O aço inoxidável AISI 444 apresentou alta potencialidade para uso como biomaterial, especialmente na fabricação de componentes protéticos com fixação magnética. / Ferritic stainless steels are ferromagnetic materials. This property does not allow their use in orthopedic prosthesis. Nevertheless, in some specific applications, this characteristic is very useful, such as, for fixing dental and facial prostheses by using magnetic attachments. In this study, the corrosion resistance and cytotoxicity of the AISI 444 ferritic stainless steel, with low nickel content, extra-low interstitial levels (C and N) and with the addition of Ti and Nb as stabilizers, were investigated to evaluate its potentiality for biomaterials fabrication. The ISO 5832 austenitic stainless steel (SS) and a commercial universal keeper for dental attachment (Neo-magnet System) were evaluated for comparison reasons. The first stainless steel is the most used metallic material for orthopedic prostheses fabrication, and the second one, is a ferromagnetic keeper for dental prostheses (NeoM). In vitro cytotoxicity analysis was performed by the red neutral incorporation method. The results showed that the AISI 444 stainless steel is non cytotoxic. The corrosion resistance was studied by anodic polarization methods and electrochemical impedance spectroscopy (EIS), in a saline phosphate buffered solution (PBS) at 37 °C, either naturally aerated or under crevice condition. A new device was developed to simulate the crevice condition on electrochemical tests. The electronic properties of the passive film formed on AISI 444 SS were evaluated by the Mott-Schottky approach. All tested materials showed passivity in the PBS medium and the passive oxide film presented a duplex nature. In aerated condition, the resistance to pitting corrosion associated to AISI 444 SS was similar to that of the ISO 5832 SS and both were superior to that of the NeoM SS. The 444 SS oxide film showed lower dopants concentration than the NeoM SS, suggesting that the 444 SS film presents a higher resistance to charge transfer through it than the fim on the NeoM SS. Under crevice conditions, the potentiodinamic polarization tests indicated low corrosion rates for both steels, but slightly higher for the ISO 5832 SS when compared to the AISI 444 SS tested. Observation of the surface, after crevice polarization, indicated a larger area of corrosive attack on the ISO 5832-1 SS than on the AISI 444 SS.The chemical composition of the NeoM SS was out of the standard specification. The low levels of Cr and Mo in the NeoM, and the high concentration of MnS precipitates, are the probable cause of its lower corrosion resistance. The new devide proposed for crevice corrosion resistance evaluation, showed good reproducibility of results.The AISI 444 stainless steel showed a high potential for use as a biomaterial, especially for the manufacture of prosthetic components with magnetic attachment.

A contaminação dos implantes e seus componentes protéticos por patógenos específicos, ainda é um problema a ser resolvido na Implantodontia. Nanoestruturas associadas à prata, aplicadas em superfície de titânio, têm sido investigadas e vêm demonstrando inibir significativamente a adesão, crescimento e colonização de uma vasta gama de microrganismos patogênicos, inclusive os resistentes a antibióticos. O objetivo deste experimento foi verificar a presença de toxicidade de nanoestruturas associadas à prata, aplicadas à superfície de titânio, frente a cultura de osteoblastos, visando desenvolver um material biocompatível, promissor na corrida pela prevenção da colonização bacteriana dos implantes. Discos de titânio comercialmente puro foram revestidos com três tipos diferentes filmes nanoestruturados. As amostras foram expostas a culturas de linhagens imortalizadas de osteoblastos (MC3T3-E1) e submetidas a ensaios de toxicidade direta (MTT), após 24h, 48h e 72h de incubação, a fim de determinar a taxa de proliferação e redução da viabilidade celular. Além disso, para verificar adesão e morfologia celular, foi realizada Microscopia Eletrônica de Varredura (MEV) após 24h de incubação. No ensaio de toxicidade celular MTT, após 48h de incubação, as superfícies nanoestruturadas, nomeadas TiAg, TiAA e SiO2, comportaram-se de maneira muito similar ao grupo controle de titânio puro (Ti) (p<0,05). O grupo SiO2 registrou maior absorbância em 24h, com diferença relevante em relação a todos os outros grupos (testes e controles). Em MEV foram verificadas uma morfologia celular compatível com viabilidade e presença de adesão dos osteoblastos em todas as superfícies testadas, similar aos grupos controles. Dessa forma, verificou-se que os três filmes nanoestruturados demonstraram biocompatibilidade a osteoblastos. / Contamination of implants and their prosthetic components by specific pathogens is still a problem to be solved in Implantology. Nanostructures associated to silver applied on titanium surface have been investigating, and have showing to inhibit significantly the adhesion, and growth of a broad range of pathogenic microorganisms, including antibiotic-resistant ones. The aim of this experiment was to verify the presence of toxicity in nanostructures associated to silver applied to titanium surface against osteoblast culture, in order to develop a biocompatible promising material in the race for prevention on implants bacterial colonization. Each commercially pure titanium disk received one of three different nanostructured films: SiO2, TiAg, and TiAA. Samples have exposed to cultures of immortalized lines osteoblasts (MC3T3-E1), and submitted to direct toxicity assay (MTT) after 24h, 48h and 72h of incubation to determine the proliferation rate and cell viability reduction. Furthermore, to verify adhesion and cell morphology, Scanning Electron Microscopy (SEM) has performed after 24h incubation. The 48h MTT cell toxicity assay showed similarity in results among test surfaces and pure titanium control group (Ti) (p <0.05). The SiO2 group registered higher absorbance in 24h, with significant difference regarding to all other groups (tests and controls). SEM exhibited cell morphology indicative of viability, and presence of osteoblast adhesion on all test surfaces, similar to control groups. Thus, it found of that three nanostructured films demonstrated osteoblasts compatibility.

Para a produção de compósitos multifuncionais crescente atenção tem sido dada a uma homogeneização eficaz de hidroxiapatitas em matrizes poliméricas, buscando uma sintonia fina da concentração entre polímeros biodegradáveis e biocerâmicas. Este trabalho dedicou-se a síntese, caracterização e estudo das propriedades biológicas do híbrido hidroxiapatita / poli(&epsilon;-aprolactona) estrela. A hidroxiapatita nanométrica (HAPN) foi revestida com o polímero biodegradável poli(&epsilon; -caprolactona) de topologia em estrela de três braços (PCLE). O uso de um polímero com topologia ramificada visa alterar algumas de suas propriedades mecânicas, a adesão interfacial à cerâmica, a sua viscosidade, o volume hidrodinâmico e sua cinética de degradação. O desempenho do híbrido HAPN/PCLE foi comparado com os materiais: HAP com partículas micrométricas (HAP-91 material comercial), o seu compósito revestido com PCLE (HAP-91/PCLE) e uma cerâmica nanométrica bifásica hidroxiapatita/&beta;-TCP (HAP-8). Os materiais foram caracterizados por avaliações físico-químicas e biológicas realizadas por estudos de citotoxicidade, adsorção de proteínas, proliferação celular, atividade de fosfatase alcalina. A síntese de PCLE foi verificada por análise espectroscópica (espectroscopia no infravermelho-FTIR; ressonância magnética nuclear de prótons- 1H-RMN e carbono- 13C-RMN; a matriz assistida por desorção a laser / ionização; MALDI-TOF; e cromatografia de permeação em gel (GPC). O revestimento das biocerâmicas por PCLE foi confirmado por técnicas de microscopia eletrônica de transmissão (MET) e de varredura (MEV). Os compósitos mostraram uma melhor trababilidade em relação à cerâmica pura e são menos quebradiços, possivelmente devido à presença do PCLE na interface da biocerâmica. A análise de MEV e MET mostrou um aspecto de continuidade no contorno das partículas de cerâmica, em micro e nano-escala. Os compósitos apresentam comportamento não citototóxico e propiciaram um crescimento de células de mamíferos. A proliferação de células osteoblásticas (MG -63) foi significativamente mais elevada para o compósito HAPN/PCLE em comparação com outros biomateriais, sugerindo influência da área de superfície na adesão e proliferação de células. O estudo do ângulo de contato indicou que o revestimento com PCLE faz com que a superfície da biocerâmica seja mais hidrofóbica. O estudo com radioisótopos indicou que o revestimento da biocerâmica com PCLE altera significativamente a adsorção das proteínas do sangue fibrinogênio e albumina. O processo de regeneração do tecido ósseo foi estudado em condições in vivo com a implantação de pastilhas dos materiais estudados em tíbias de coelho. Os resultados mostraram que os compósitos podem ser utilizados como biomaterial, pois houve neoformação óssea ao redor dos implantes. / For the production of multifunctional composites in the combination of biodegradable polymers and bioceramics, increasing attention has been paid to an effective homogenization of hydroxyapatite within polymer matrices and a fine tuning of the concentration. This work was dedicated to the synthesis, characterization and study of the biological properties of the hybrid star poly(&epsilon;-caprolactone)/hydroxyapatite composites. A nanometer hydroxyapatite (HAPN) was coated with the biodegradable polymer poly (&epsilon;-caprolactone) with three arms star topology (PCLE). The use of polymer branched topology aims to change some of its mechanical properties, the interfacial adhesion to ceramic, its viscosity, the hydrodynamic volume and its degradation kinetics. The performance of the hybrid HAPN/PCLE was compared with the other three materials: HAP commercial micrometric particles (HAP-91), their composite coated with PCLE (HAP-91/PCLE) and a biphasic ceramic nanohydroxyapatite/&beta;-TCP (HAP-8). All materials were characterized by different physico-chemical and biological evaluations performed by cytotoxicity studies, protein adsorption, cell proliferation, alkaline phosphatase activity and an in vivo studies. The synthesis of PCLE was verified by spectroscopic analysis (Fourier-Transform infrared-FTIR and nuclear magnetic resonance-1H-NMR/13C-NMR), matrix-assisted laser desorption/ionization (MALDI-TOF) and gel permeation chromatography (GPC). The coating of the bioceramics by PCLE was confirmed by microscopy techniques transmission electron microscopy (TEM) and scanning electron microscopy (SEM). The composites showed better easy handling in relation to pure ceramic and are less brittle, possibly due to the presence of PCLE at bioceramic interface. The SEM and TEM analysis showed an aspect of continuity in the contour of the ceramic particles, both in micro and nanoscale. The composites exhibit non cytotoxicity behavior and propitiated mammalian cell growth. The proliferation of osteoblastic cells (MG-63) was significantly higher for the composite HAPN/PCLE compared to other biomaterials, suggesting influences of the surface area on the cell adhesion and proliferation. The study of contact angle indicated that the PCLE coating makes the bioceramic surfaces more hydrophobic. The radioisotopic studies indicates that the coating of bioceramics with PCLE significantly alter the adsorption of blood proteins fibrinogen and albumin. The process of regeneration of bone tissue was studied in in vivo conditions after implantation of implants manufactured from composites in rabbit´s tibias. The results showed that composites can be used as biomaterial since the newly bone grew around the implants.

Biomateriais metálicos devem apresentar uma combinação de propriedades como resistência à corrosão, biocompatibilidade e resistência mecânica. Os aços inoxidáveis austeníticos, especialmente do tipo AISI 316L, aliam estas propriedades com a possibilidade de fabricação a um baixo custo. No entanto, são susceptíveis à corrosão nos fluidos fisiológicos e seus produtos de corrosão podem causar reações alérgicas ou infecciosas nos tecidos vizinhos ao implante. No presente trabalho, a aplicação de revestimentos obtidos por processos de deposição física de vapor (PVD) sobre um aço inoxidável austenítico do tipo AISI 316L foi realizada a fim de aumentar sua resistência à corrosão e biocompatibilidade. Os filmes depositados foram de nitreto de titânio (TiN), carbonitreto de titânio (TiCN) e de carbono tipo diamante (DLC). Estes materiais têm alta dureza e resistência ao desgaste, além de biocompatibilidade intrínseca, características altamente desejáveis para aplicações biomédicas. A caracterização do comportamento eletroquímico do aço com os três tipos de revestimentos mostrou que a presença de defeitos na superfície das camadas depositadas exerce uma influência negativa sobre a resistência à corrosão do substrato. A presença dos defeitos foi evidenciada por microscopia eletrônica de varredura. Foi proposto um mecanismo, com base nos dados obtidos por espectroscopia de impedância eletroquímica, para explicar a evolução do comportamento eletroquímico do aço com os diferentes revestimentos ao longo do tempo de imersão. Foram também empregados dois tratamentos de passivação da superfície do aço em soluções de ácido sulfúrico e ácido nítrico, a fim de aumentar a resistência à corrosão do substrato. Os resultados indicaram que os tratamentos utilizados não foram eficientes para melhorar esta característica, mas podem ser modificados visando um desempenho superior. As propriedades eletrônicas dos filmes passivos formados, tanto sobre o aço sem tratamento de passivação como sobre o aço passivado, foram estudadas utilizando a abordagem de Mott-Schottky. Os filmes apresentaram um caráter duplex, mostrando comportamento de um semicondutor altamente dopado acima e abaixo do potencial de banda plana. A concentração de dopantes no filme passivo foi associada à resistência à corrosão do material. Os três revestimentos PVD investigados apresentaram comportamento não citotóxico. Considerando a diminuição do coeficiente de atrito do aço 316L, os revestimentos de TiCN e o DLC foram os mais eficientes. Estas características, aliadas ao fator custo, sugerem que a aplicação comercial destes materiais sobre implantes ortopédicos pode ser viável. No entanto, a resistência à corrosão, conforme a avaliação realizada no presente estudo, não foi adequada quando comparada ao desempenho do aço sem nenhum tipo de revestimento. Ao final do texto, são apresentadas algumas sugestões a fim de conseguir um desempenho superior para a capacidade protetora dos revestimentos PVD. / Metallic biomaterials must present a combination of properties such as corrosion resistance, biocompatibility and mechanical resistance. Austenitic stainless steels, especially AISI 316L combine these properties with the easy of fabrication at low cost. However, they are prone to corrosion in physiological solutions. Furthermore, their corrosion products may lead to infectious ou allergenic reactions in the tissues around the implant device. In the present work, coatings produced by physical vapour deposition (PVD) methods have been applied on the surface of a 316L stainless steel to increase its corrosion resistance and biocompatibility. Three thin films were tested: titanium nitride (TiN), titanium carbonitride (TiCN) and diamond-like carbon (DLC). These materials present high hardness, wear resistance and intrinsic biocompatibility that are key features when considering biomedical applications. The characterization of the electrochemical behavior of the stainless steel coated with the three different films showed that the presence of surface defects are deleterious to the corrosion resistance of the substrate. These defects were observed using scanning electron microscopy. The evolution of the electrochemical behavior of the coated steel was explained through a mechanism based on the experimental results obtained using electrochemical impedance spectroscopy. Two different passivation treatments were carried out on the stainless steel surface, either in sulfuric or nitric acid solutions, to increase its corrosion resistance. The results suggested que these treatments were not efficient, but may be modified to improve its performance. The electronic properties of the passive films of the non-passivated and passivated stainless steel were studied using the Mott-Schottky approach. The films presented a duplex character. Below the flatband potential the behavior is typical of a highly doped type-p semiconductor. Above the flatband potential is typical of a highly doped type-n semiconductor. The doping concentration in the passive film was determined and associated with the corrosion resistance of the substrate. All PVD coatings investigated showed non-cytotoxic behavior. DLC and TiCN coatings decreased the friction coefficient of the stainless steel substrate. These properties allied with the stainless steel low cost recommend their commercial use for implants materials purposes. Nevertheless the corrosion resistance presented by the coated-steel was inferior to that of the bare steel and should be improved. At the end of the present text, some suggestions are proposed in order to improve the corrosion protection performance of the PVD coatings.