Orientadores: Ângela Maria Moraes, José Alberto Fracassi da Silva / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia Química / Made available in DSpace on 2018-08-19T03:16:00Z (GMT). No. of bitstreams: 1 RammazzinaFilho_WalterAnibal_M.pdf: 10957404 bytes, checksum: d23a9aea438343039da493db09603556 (MD5) Previous issue date: 2011 / Resumo: O uso de implantes em cirurgias de correção da parede abdominal é freqüentemente necessário. Telas de poli(propileno) podem ser empregadas com sucesso para essa finalidade, possuindo boa aceitação tecidual e baixo custo. O uso deste tipo de biomaterial pode, porém, ocasionar a aderência indesejada entre tecidos e/ou entre órgãos como o fígado e os intestinos e a tela, resultando em dores abdominais, obstrução intestinal e infertilidade. Neste contexto, o objetivo deste trabalho foi o de desenvolver uma estratégia de recobrimento de telas de poli(propileno) enfocando a deposição de soluções de quitosana de massa molar baixa e média e de polietilenoglicol (PEG) de massa molar igual a 1000 Da por electrospinning. Para fins de comparação, telas de poli(propileno) foram alternativamente recobertas por imersão com diferentes soluções combinando quitosana e PEG. Nos estudos de recobrimento via electrospinning, foram avaliadas as variáveis tipo de solvente para a dissolução da quitosana e do PEG, vazão de solução de recobrimento, proporção entre quitosana e PEG, diferença de potencial usada durante a deposição e distância entre a tela e o jato de injeção. As telas recobertas através da imersão em soluções de quitosana a 1% (tanto com a de baixa massa molar quanto a com massa molar média) e em soluções de quitosana misturada ao PEG também com concentração de sólidos total de 1% apresentaram-se satisfatórias para fins de barreira física em cirurgias de hérnia, considerando-se o aspecto, a uniformidade, os valores médios de espessura (de 1140 e 990 mm, respectivamente), a perda de massa em fluido corpóreo simulado (5,1 e 8,9%, respectivamente) e a capacidade de absorção do mesmo fluido (0,76 e 0,59 g/g, respectivamente). Já o recobrimento por electrospinning resultou no depósito de fibras emaranhadas na superfície das telas, que apresentaram, então espessuras finais variando entre 581 e 612 mm, perdas de massa entre 4,9 e 9,2% em fluido corpóreo simulado, capacidade de absorção de 0,17 a 0,36 g/g em fluido corpóreo simulado e diâmetros de fibras de 20,9 a 92,2 mm. O recobrimento via electrospinning resultou em biomateriais menos espessos e com menos massa associada, com bom potencial de uso na aplicação pretendida / Abstract: The use of implants in surgical correction of the abdominal wall is frequently required. Polypropylene meshes can be successfully employed for this purpose, having good tissue acceptance and low cost. The use of this biomaterial, however, can lead to undesired adhesion between tissues and/or between organs such as the liver and intestines and the mesh, resulting in abdominal pain, bowel obstruction and infertility. In this context, the objective of this work was to develop different coatings of polypropylene meshes, focusing on the deposition of solutions of chitosan of low and medium molecular weight and polyethylene glycol (PEG) of molecular weight equal to 1000 Da by electrospinning. For comparison, polypropylene meshes were alternatively coated by immersion in different solutions combining chitosan and PEG. In the studies of coating via electrospinning, the effect of the variables type of solvent for the dissolution of chitosan and PEG, coating solution flow rate, chitosan to PEG mass ratio, the potential difference used during the deposition and the distance between the mesh and the injection jet were evaluated. Meshes coated by immersion in chitosan (both with low and medium molar mass) and PEG solutions with total solids concentration of 1% were satisfactory for purposes of physical barrier in hernia surgery, considering aspect, uniformity, mean thickness (1140 and 990 mm, respectively), mass loss (5.1 and 8.9%, respectively) and the capacity of fluid absorption (0.76 and 0.59 g/g, respectively). Coating by electrospinning resulted in the deposition of entangled fibers on the surface of the meshes, which had final thickness ranging between 581 and 612 mm, losses of mass between 4.9 and 9.2% in simulated body fluid, absorption capacity of 0.17 to 0.36 g/g in the same fluid and fiber diameters from 20.9 to 92.2 mm. Coating the meshes via electrospinning resulted in thinner biomaterials and with less associated mass, with good potential for use in the intended application / Mestrado / Desenvolvimento de Processos Biotecnologicos / Mestre em Engenharia Química

Orientadores: William Dias Belangero, Vanessa Petrilli Bavaresco / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-19T13:54:42Z (GMT). No. of bitstreams: 1 Batista_NilzaAlzira_M.pdf: 2999795 bytes, checksum: 62c4ef5808533e1bb33930f97cede278 (MD5) Previous issue date: 2011 / Resumo: Hidrogel de álcool de polivinil (PVA) foi utilizado como potencial reparador de defeitos osteocondrais da cartilagem articular. A citotoxicidade in vitro foi avaliada com células Vero e células-tronco mesenquimais da medula óssea de ratos Wistar-Kyoto. Para análise in vivo, os implantes foram colocados em defeitos produzidos nos joelhos de ratos Wistar. Após tempos de seguimento de 0, 3, 6, 12 e 24 semanas, as amostras foram analisadas por microscopia óptica convencional, ensaio mecânico de fluência à indentação, espectrometria de fluorescência raio X e microscopia eletrônica de varredura. Os resultados in vitro motraram que o hidrogel de PVA não afetou a atividade metabólica de ambas as células estudadas, nem tampouco a diferenciação osteogênica das células mesenquimais. Atividade da enzima fosfatase alcalina e formação de matriz mineralizada foram identificadas. O PVA implantado não apresentou sinais de desgastes ou qualquer mudança de aspecto quando comparado com o dia do implante. A interface do implante/tecido mostrou a formação e manutenção de tecido conjuntivo denso e osso recém-formado em todos os grupos estudados. Foi observado um aumento no módulo de fluência e concentração de cálcio e fósforo no PVA longo do tempo. O desempenho do higrogel de PVA irradiados e acetalizadas foi considerado satisfatório para a aplicação proposta / Abstract: Irradiated and acetalized polyvinyl alcohol (PVA) hydrogel was investigated as a potential material for osteochondral defect repair in articular cartilage. The in vitro cytotoxicity of the material was evaluated with Vero cells and mesenchymal stem cells from bone marrow of Wistar-Kyoto rats. For in vivo analyses, plugs of the material were implanted into defects produced in the knees of male Wistar rats-WH. After follow-up times of 0, 3, 6, 12 and 24 weeks, the samples were analyzed by conventional optical and scanning electron microscopy, X-ray fluorescence spectrometry and submitted to mechanical testing of creep indentation. The in vitro results suggest that the PVA hydrogel did not affect the viability and morphology of any of the cell types studied. The hydrogel affected neither the metabolic activity of both studied cells nor the osteogenic differentiation of the mesenchymal cells. Activity of alkaline phosphatase and mineralized organic matrix formation could be identified. The implanted plugs showed no sign of wear or aspect change. The interface plug/tissue exhibited dense connective tissue and newly formed bone in all groups. It was observed an increase in the creep modulus and in the concentration of calcium and phosphorus in the PVA over time. The performance of the irradiated and acetalized PVA was considered satisfactory for the proposed application / Mestrado / Fisiopatologia Cirúrgica / Mestre em Ciências

Orientador: João Batista Fogagnolo / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia Mecânica / Made available in DSpace on 2018-08-20T18:12:15Z (GMT). No. of bitstreams: 1 SallicaLeva_Edwin_M.pdf: 25527220 bytes, checksum: e74531ec342d519e6163a514595cb183 (MD5) Previous issue date: 2012 / Resumo: Peças fabricadas em titânio com estrutura porosa apresentam vantagens como material para implantes basicamente pela redução do módulo de elasticidade, o que aproxima sua rigidez à de tecidos ósseos, tornando-as mais adequadas á sua função. Neste trabalho apresenta-se um estudo da microestrutura e propriedades mecânicas de peças porosas de Ti-6Al-4V fabricadas por sinterização seletiva a laser, que é uma das técnicas de prototipagem rápida, que consolida, camada a camada, peças com geometria complexa a partir de pó. As estruturas porosas foram modeladas em programa CAD e fabricadas em um equipamento EOSINT M 270. Os modelos computacionais têm forma cúbica com 15 mm de aresta e possuem arquitetura interna de poros interconectados também de forma cúbica. A porcentagem de porosidade foi variada na faixa de 61 a 76%, mudando-se o número e o tamanho dos poros e a espessura das paredes internas. Pó atomizado da liga Ti-6Al-4V foi utilizado como matéria-prima. Utilizaram-se dois níveis de energia fornecida, variando-se alguns parâmetros do processo, como a velocidade de varredura do feixe de laser, a potência do laser e distância entre linhas de sinterização. As amostras sinterizadas foram caracterizadas por microscopia óptica e eletrônica de varredura, ensaios de dureza e compressão. Em uma segunda etapa, foram realizados tratamentos térmicos em amostras com 69% de porosidade projetada. As peças sinterizadas apresentaram microestrutura martensítica, porosidade interconectada na faixa de 63 a 77%, com boa formação de parede, e superfície rugosa com aderência de partículas de pó não sinterizado. Testes de compressão das amostras sinterizadas mostraram que o módulo de Young variou de 5,36±0,01 a 8,73±0,07 GPa, o limite de escoamento variou de 91,5±0,7 a 170±5 MPa e a resistência mecânica à compressão variou de 106±1 a 219±5 MPa, dependendo da porcentagem de porosidade. O aumento da energia do processo resultou em paredes mais finas, para o mesmo modelo, e também uma porosidade não controlada, interna às paredes das peças, o que reduziu a rigidez e a resistência mecânica das peças. Os tratamentos térmicos feitos nas peças porosas com 69 % de porosidade projetada promoveram mudanças microestruturais, mas não resultaram em aumento das propriedades mecânicas / Abstract: Titanium porous parts have advantages as materials for implants due to their lower modulus of elasticity, which approximates their stiffness to the bone tissue stiffness, making them more appropriate to their biofunction. In this work we present a microstructural characterization and a mechanical property evaluation of porous parts of Ti-6Al-4V produced by selective laser sintering, which is a rapid prototyping technique that consolidates, layer by layer, parts with complex geometry from powder. The porous structures were designed in a CAD program and manufactured in the EOSINT 270 laser-sintering system. The computational models have cubic shape with 15 mm edge and an internal architecture of interconnected pores also with cubic shape. The percentage of porosity was varied in the range from 61 to 76 % by changing the number and size of the porous and the thickness the struts. Powder prealloyed of Ti-6Al-4V was using as raw material. Two energy levels were tested, by varying the process parameters, such as laser power, speed of laser and spacing between laser tracks. The as-sintered samples were characterized by optical and scanning electron microscopy, hardness and compressive tests. Further, thermal treatments were performed on samples with 69% of modeled porosity. The sintered parts presented martensitic microstructure, with interconnected porosities varying from 63-77%, with good formation of struts, and rough surface with adhesion of no-sintered powder particles. The compression tests of as- sintered samples showed the Young's modulus values ranging from 5.36 ± 0.01-8.73 ± 0.07 GPa, the yield strength values ranging from 91.5 ± 0,7-170 ± 5 MPa and the compressive strength values ranging from 106 ± 1-219 ± 5 MPa, depending on the percentage of porosity. Increasing the energy of the process resulted in thinner struts for the same model and also a no-controlled porosity in the internal struts of parts, which reduced the stiffness and the mechanical strength of the parts. Heat treatments performed in the porous parts with 69% porosity promoted microstructurals changes, but did not result in an increase of the mechanical properties / Mestrado / Materiais e Processos de Fabricação / Mestre em Engenharia Mecânica

Lesões na cartilagem articular do joelho são patologias frequentes e geralmente causadas por traumas. Apesar de algumas serem assintomáticas, essas alterações osteocondrais podem evoluir para degeneração da cartilagem articular e osteoartrose. Uma da degeneração progressiva da cartilagem articular leva a osteoartrite (OA), comumente sendo a articulação femorotibiopatelar a mais afetada. Como os tratamentos convencionais para OA não são curativos, apenas paliativos, a terapia celular com células-tronco (CT) desponta como alternativa. Neste trabalho utilizamos células-tronco de dente decíduo esfoliado (Stem cells from Human Exfoliated Deciduous teeth - SHED), cultivadas em associação com um biomaterial, para tratar lesões osteocondrais provocadas em joelhos de ovinos. Quatro defeitos osteocondrais foram cirurgicamente produzidos para testar quatro condições: 1) SHED associada ao biomaterial, 2) somente biomaterial, 3) somente SHED e 4) nenhum tratamento (controle). Os ovinos foram acompanhados clinicamente e através de exames radiográfico, US e artroscopia, por 120, 190, 365 e 730 dias até a eutanásia. Os resultados revelaram que o tratamento com biomaterial em associação com SHED, produziu reparo similar à estrutura cartilagínea a partir de 190 dias, apresentando características de cartilagem adjacente. Entretanto, apesar dos resultados positivos em relação ao reparo da lesão osteocondral, não foi possível afirmar se a melhora deveu-se a diferenciação direta das SHED para células presentes na cartilagem ou se foi um efeito parácrino das mesmas. Em tempo, não foi observada rejeição e nenhuma reação adversa ao implante celular xenogênico durante o período experimental. / Articular cartilage injuries on the knee are frequent pathologies and usually caused by trauma. Although some are asymptomatic, these changes may evolve into osteochondral articular cartilage degeneration and osteoarthritis. A progressive degeneration of articular cartilage leads to osteoarthritis (OA), being femorotibiopatelar joint the most affected one. As conventional treatments for OA are not curative, but palliative, cell therapy with stem cells (SC) stands out as an alternative. In this work we used stem cells from human exfoliated deciduous teeth (SHED), grown in association with a biomaterial, to treat osteochondral lesions on sheep\'s knees. Four osteochondral defects were surgically produced to test four conditions: 1) SHED associated with the biomaterial, 2) only the biomaterial, 3) only SHED and 4) no treatment (control). The sheep were followed clinically and through radiographic exams, US and arthroscopy, for 120, 190, 365 and 730 days until euthanasia. The results showed that treatment with biomaterial in combination with SHED produced repair similar to the cartilage structure from 190 days, showing cartilage adjacent features. However, despite the positive results in relation to the repair of osteochondral lesion it was not possible to say whether the improvement was due to direct differentiation of SHED for cells present in cartilage or was a paracrine effect. In time, there was no rejection and no adverse reaction to the xenogenic cell implant during the trial period.

Les prothèses diaphragmatiques en ePTFE utilisées dans la hernie diaphragmatique congénitale à large défect ont une faible étirabilité, ce qui entrainera des récidives herniaires au cours de la croissance de l’enfant. En effet, l’analyse en imagerie montre que la surface du diaphragme grandit de 4-5 fois jusqu’à l’adolescence. De plus, les mesures de rigidité des surfaces de prothèses explantés, montrent l’influence des contraintes mécaniques appliquées sur la structure des matrices extracellulaires néoformées. Afin de favoriser l’intégration tissulaire du ePTFE, nous avons testé un moyen de fonctionnaliser le ePTFE avec la polydopamine sur une seule face. Le revêtement nanoscopique favorise la colonisation cellulaire. Enfin, ce travail de thèse présente une méthode originale de réalisation d’une nouvelle membrane bicouche avec des propriétés mécaniques conformes aux exigences chirurgicales. Ce biomatériau innovant et prometteur fait actuellement l’objet d’une Déclaration d’invention. / Electron microscopy assessments of ePTFE prosthesis explants for diaphragmatic congenital hernia repair strongly suggest that the tissue responses are directly related to the surface microstructure of the biomaterial. AFM measurements (Young moduli) emphasize the influence of the mechanical stress applied to the implant on the mechanical properties of the newly formed extracellular matrices. In order to guide the host responses, we undertook to functionalize with polydopamine the ePTFE biomaterial. Electron microscopy investigations reveal the interest of that surface treatment regarding cell colonization of implant. To optimize that approach, we developed an original method aimed to coat only one face of the biomaterial. After determination of the growth rate of the diaphragm from birth to adolescence, we explored the possibility to design a new double-faced mesh able to follow body growth. From this point of view, the initial prototypes are promising and under patent application.

Common biodegradable polyesters such as poly(lactic acid) (PLA), poly(lactic-co-glycolic acid) (PLGA) and poly(ε-caprolactone) (PCL) are used as drug delivery vehicles for tissue regenerative applications. However, they are typically bioinert, with drug loading limitations. Polymerizing the active agent or precursor into its respective biodegradable polymer would control drug loading via molar ratios of drug to initiator used for synthesis. Simvastatin was chosen due to its favorable anti-inflammatory, angiogenic, and osteogenic properties. In addition, its lactone ring lends itself to ring-opening polymerization and, consequently, the synthesis of poly(simvastatin) with controlled simvastatin release. Simvastatin was first polymerized with a 5kDa methyl-terminated poly(ethylene glycol) (mPEG) initiator and catalyzed via stannous octoate to form poly(simvastatin)-block-poly(ethylene glycol). Molecular weights ranged from 9.5kDa, with a polydispersity index (PDI) of 1.1 at 150 °C, to 75kDa with a PDI of 6.9 at 250 °C. First-order propagation rates were seen. Infrared spectroscopy showed carboxylic and methyl ether stretches unique to simvastatin and mPEG in the copolymer, respectively. Slow degradation was seen in neutral and alkaline conditions, with simvastatin, simvastatin-incorporated macromolecules, and mPEG identified as degradation products. Alternatively, triazabicyclodecene (TBD) was used to mediate simvastatin polymerization. A lower temperature of 150°C led to successful polymerization using 5kDa mPEG, compared to at least 200 °C via stannous octoate. TBD was also successful for reactions using 2 or 0.55kDa mPEG. The biodegradability of poly(simvastatin)-block-poly(ethylene glycol) via TBD improved, losing twice more mass in phosphate-buffered saline, pH 7.4, than the copolymer synthesized via stannous octoate. Release rates of three different copolymers synthesized demonstrated tunable simvastatin release. To further modulate degradation, poly(simvastatin)-block-poly(ethylene glycol) was blended with 5, 2, or 0.55kDa mPEG-initiated PLA copolymers. The blends showed a compressive elastic modulus ranging from 26 to 44MPa, within the magnitude of trabecular bone (approximately 50MPa). Tunability in mass loss and release was also seen due to varied ratios of incorporated PLA copolymers. Lastly, copolymer degradation byproducts inhibited HMG-CoA reductase and showed possible enhancement of osteoblastic activity in vitro. A pilot study using a rodent calvarial onlay model showed tolerability of the polymers and potential for long-term evaluations of bioactivity. Poly(simvastatin) may be useful in regenerative applications.

L'intérêt pour le développement de ciments osseux à base de phosphates de calcium (CaP) en tant que systèmes de délivrance de médicament a augmenté en raison de sa capacité à être injecté et à permettre un traitement local et contrôlé des maladies ou défauts osseux. A cette fin, nous nous sommes intéressés à la formulation d’un ciment mixte à base de carbonate et phosphate de calcium (CaCO3-CaP) chargé avec différentes teneurs (3, 6 et 9% calculé par rapport à la masse de la phase solide du ciment) en acide fusidique (AF), composé pratiquement insoluble dans l’eau, ou en son sel hydrosoluble, le fusidate de sodium (SF). L’influence de l’incorporation de l’antibiotique sous ces deux formes sur les propriétés physicochimiques (temps et cinétique de prise, résistance à la compression, injectabilité) et la microstructure (porosité) du ciment ainsi que sur la libération in vitro de ce médicament a été étudiée. L’effet de la quantité d’eau (rapport liquide/solide (L/S)) utilisée pour l’élaboration du ciment sur ces propriétés a été également examiné. Les résultats obtenus ont révélé que l'ajout de l’antibiotique n’avait aucun effet sur la composition minérale du ciment durcit : la réaction de prise donne lieu à la formation d’une apatite carbonatée analogue au minéral osseux. Nous avons observé que le temps de prise du ciment a été prolongé par l’addition d’AF, tandis que la présence de SF le réduit et cet effet est dose dépendant. L’utilisation d’un accélérateur de prise (Na2HPO4) réduit le temps de prise d’une manière significative, et a permis d’atteindre un temps de prise de l’ordre de 25 à 30 minutes ; celui-ci se situe dans une gamme compatible avec une application en chirurgie orthopédique ou dentaire. Ce travail a également permis de mettre en évidence que l’incorporation de l’antibiotique dans le ciment s’accompagne d’ une diminution de la porosité et de la résistance à la compression. En outre, l’augmentation du rapport liquide-solide (L/S) se traduit par une augmentation du temps de prise, de la porosité des ciments et par une diminution de la résistance à la compression. Les mesures d’injectabilité des ciments étudiés ont montré que la charge nécessaire pour l’extrusion de la pâte est diminuée par l'ajout d’AF (injectabilité améliorée) et que cet effet est amplifié en présence de SF. Le phénomène de séparation de phases qui limitait l’injectabilité de la pâte du ciment de référence a été supprimé par l’ajout de 9 % de SF et par l’augmentation de la quantité d’eau utilisée (L/S plus élevé) pour l’élaboration du ciment. Les essais de libération in vitro du principe actif dans une solution de NaCl 0.9 % à 37°C pendant un mois montrent que la libération est prolongée et ce quels que soient la forme de l’antibiotique et le rapport L/S. Le taux libéré est lié à la porosité totale et à la taille des pores du ciment ainsi qu’à la solubilité de l'antibiotique. Les quantités libérées par jour sont de l’ordre de 0.5 à 2 mg/L. La libération du médicament a été modélisée en utilisant les équations de Korsmeyer-Peppas, de Higuchi ou de Kopcha. Les résultats ont montré que la libération du médicament est contrôlée principalement par un mécanisme de diffusion. Enfin, l’efficacité in vitro du système de délivrance préparé a été évaluée à travers des essais microbiologiques réalisés avec les ciments chargés en antibiotique ; les résultats préliminaires obtenus ont montré une activité anti-biofilm faible sur la souche bactérienne de type Staphylococcus aureus. / The interest in developing calcium phosphate cements as a drug delivery system has risen because of its capability to be injectable and to enable local and controlled treatment of bone disease or defects. In the present work, we are interested in the development of a mixed cement based on calcium phosphate and carbonate (CaCO3-CaP) loaded with different concentrations (3, 6 and 9% calculated on the weight of the cement solid phase) of fusidic acid (FA) compound substantially insoluble in water, or its water soluble salt, sodium fusidate (SF). The influence of the incorporation of both forms of antibiotic on the physicochemical properties (setting time and setting reaction kinetics, compressive strength, injectability) and the microstructure (porosity) of the cement as well as on the in vitro release of this drug was studied. The effect of the amount of water (liquid / solid ratio (L / S)) used for the preparation of cement on these properties was also examined. The results obtained showed that the addition of the antibiotic had no effect on the final composition of the hardened cement: the setting reaction leads to the formation of a carbonated apatite analogous to bone mineral. The setting time of the cement was prolonged by the addition of AF, while it is reduced in the presence of SF and we showed that this effect is dose-dependent. The introduction of an accelerator (Na2HPO4) in the cement formulation reduces the setting time significantly in a range (25 to 30 minutes) which is adapted to orthopedic and dental applications. This work has also demonstrated that the incorporation of the antibiotic in the cement is accompanied by a decrease in the cement porosity and resistance to compression. In addition, increasing the liquid to solid ratio induced an increase in the setting time and in the porosity of the cement whereas the cement compressive strength is decreased. Measurements conducted on cement injectability have shown that the load required to extrude the paste is reduced by the addition of AF (improved injectability) and this effect is enhanced in the presence of SF. The phase separation phenomenon that limits the injectability of the reference cement paste was suppressed by the addition of 9% of SF and by increasing the amount of water (higher L / S) used for the preparation of cement. In vitro release test of the antibiotic in NaCl 0.9% solution at 37 °C over one month showed that the release is sustained regardless of the form of the antibiotic and of the L / S ratio. The released rate is related to the total porosity and pore size of the cement as well as the solubility of the antibiotic. The amounts released per day are in the range of 0.5 to 2 mg /L. Drug release was modeled using the Korsmeyer-Peppas, Higuchi or Kopcha equations. These modelisations showed that the drug release is mainly controlled by a diffusion mechanism. Finally, the in vitro efficiency of the prepared drug delivery systems was evaluated through microbiological tests on antibiotic-loaded cements; the preliminary results obtained showed a weak anti-biofilm activity against Staphylococcus aureus bacterial strain.

Gene therapy involves the use of nucleic acids, either DNA or RNA for the treatment, cure, or prevention of human diseases. Synthetic cationic polymers are promising as a tool for gene delivery because of their high level of design flexibility for biomaterial construction and are capable of binding and condensing DNA through electrostatic interactions. Our lab has developed a novel polymer (poly (polyethylene glycol-dodecanoate) (PEGD), a polyester of polyethylene glycol (PEG) and dodecanedioic acid (DDA). PEGD is a linear viscous polymer that self-assembles into a vesicle upon immersion in an aqueous solution. A copolymer of dodecanedioc acid and polyethylene glycol (PEG) was synthesized at a 1:1 ratio. Furmaric (FA) or itaconic acid (IA) was used to suppress DDA in the PEGD copolymer at an 80:20 ratio (DDA: furmaric/itaconic acid) to form the PEGDF/I variant. PEGDF/I are then modified through the Michael addition of Protamine Sulfate (PEGDF/I-PS) and Cys-Arg8 (PEGDF/I-CA) peptide to the carbon-carbon double bond on the polymer backbone to introduce a positive charge. The modified PEGDF/I polymers were capable of binding and condensing DNA. Transfection of HEK 293 cells with pTurboGFP plasmid using modified PEGDF/I polymers was successful but showed varied efficiency. The PEGDF/I-CA polymer had around 30% transfection efficiency and was shown to be non-cytotoxic.

Multifunctional agents for the management of highly heterogeneous diseases, like cancer, are gaining increased interest with the intent of improving the diagnostics and therapy of cancer patients. These agents are also important because more than one treatment modality is typically used for cancer therapy in the clinic. Further, nanotechnology offers a platform where more than one agent can be combined to help provide improved cancer diagnosis and therapy. Near-infrared light-activatable phototherapeutic agents have great potential in vivo. Body tissues have minimum absorption in the near- infrared range. They also have been shown to enhance the cytotoxic effect of chemotherapeutic drugs when used in combination with them. We have, hence, investigated the potential of two multifunctional targeted nanoparticles for combined chemo-phototherapy (employing near- infrared light activable agent) and for understanding their underlying cellular responses. The first is employing polymeric Poly-lactic acid-co-glycolic acid (PLGA) nanoparticles with simultaneous incorporation of Indocyanine Green (ICG) (a near-infrared light-activatable photothermal agent) and Doxorubicin (DOX) and surface conjugated with anti-Human Epithelial Receptor-2 (HER-2). The PLGA nanoparticles were subjected to two modes of hyperthermia, incubator and laser hyperthermia, to mimic whole-body and localized hyperthermia used clinically. These nanoparticles upon laser exposure showed a rapid heat shock protein 70 (HSP70) response in comparison to the cellular HSP70 response upon incubator hyperthermia exposure. However, 12h post-treatment, downregulation of HSP70, was observed, thus, causing cellular apoptosis or necrosis based on the degree of thermal insult. These targeted nanoparticles, simultaneously incorporating agents, suffer from the limitation of release of both the agents from the nanoparticles and the need to control their release for bringing in effective therapy. Therefore, the second multifunctional nanoparticle employing silver nanoparticles (AgNPs) conjugated with Doxorubicin was formulated. AgNP serve as a near-infrared activatable agent itself, other than serving as a drug delivery vehicle. Thus, these nanoparticles only require the need to control the release of DOX alone. We further studied their mechanism of action, which included enhanced reactive oxygen species (ROS) production and reduction of intracellular thiol levels.

Because of their excellent mechanical, tribological, and electrochemical properties, Cobalt Chromium Molybdenum alloys have been used as the material for both the stem and head of modular hip implants. Corrosion is one mechanism by which metal debris, from these implants, is generated, which can lead to adverse events that requires revision surgery. Manufacturing process such as wrought, as-cast, and powder metallurgy influences the microstructure, material properties, and performance of these implants The current research focuses on analyzing the microstructure of CoCrMo alloys from retrieved hip implants with optical and scanning electron microscopy. Additionally, energy disperse spectroscopy was utilized to determine weight composition of cobalt, chromium, and molybdenum in solution. Potentiodynamic polarization was used as an accelerated corrosion testing method to determine the electrochemical behavior of the different microstructures. In agreement with prior literature, it was found that Low Carbon Wrought CoCrMo Alloys have the best corrosion resistance properties.