A progesterona é um hormônio esteróide comumente utilizado na sincronização do estro em programas de manejo reprodutivo de bovinos. Sua administração por meio de implantes auriculares compostos de nanopartículas é uma estratégia promissora para a indústria farmacêutica veterinária. Este trabalho foi delineado com o intuito de produzir e estudar a cinética de liberação da progesterona (P4) encapsulada em nanopartículas de polímeros biodegradáveis produzida por meio supercrítico (SAS). Partículas de Poli-hidroxi-butirato e valerato (PHB-V) de três diferentes tamanhos (grupos PHB-V1, PHB-V2 e PHB-V3) e suas combinações com poli-e-caprolactano (PCL; grupos PHB-V1/PCL, PHB-V2/PCL e PHB-V3/PCL) foram impregnadas com P4, pesadas, suspendidas em 10 mL de solução de etanol/água 60:40 (v/v) e colocadas em banho-maria com agitação. Nos tempos 2min; 2h, 4h, 8h, 12h, 24h e 48h foram coletadas amostras de 1 mL. Após centrifugação (2.000 g por 10 min a 37°C) as amostras foram filtradas (0,45µm) e submetidas à análise por LC-MS/MS para quantificação de P4. Foi utilizado um espectrômetro de massas tripo-quadrupolo API-4000 Q TRAP (Applied Biosystems) equipado com fonte e ESI Turbo-V. As análises foram realizadas em modo MRM em modo positivo visando monitorar as transições 315.5>109.1 e 315.5>297.2. Utilizou-se um HPLC Agilent series 1100 para eluição isocrática do analito em metanol/água 50%, em tempo total de corrida de 2,5 min. A curva de calibração foi construída com triplicatas de 1, 5, 10, 25 e 50 ng/mL de P4. A análise estatística incluiu ANOVA e interação (tamanhos de PHB-V e presença/ausência de PCL), considerando o nível de significância de 5%. Observou-se que a associação do PHB-V1/PCL aumentou a quantidade de progesterona liberada em relação ao PHB-V1 isolado. O mesmo efeito foi observado para o grupo PHB-V3/PCL. No entanto, a associação PHB-V2/PCL levou à diminuição na liberação de progesterona em relação ao PHB-V2 isolado. A cinética de liberação diferiu entre os grupos nos diferentes tempos avaliados. Dessa maneira, os resultados demonstram que diferenças de tamanho de nanopartículas de PHB-V e suas associações ao PCL podem afetar a quantidade, bem como a cinética da liberação do fármaco na liberação in vitro usando solvente álcool/água. A utilização do meio super critico para produção da partículas, proporcionou uma carga maior de P4 e alterou a cinética de liberação. / Progesterone is a steroid hormone commonly used in estrus synchronization programs in reproductive management of cattle. His administration through ear implants composed of nanoparticles is a promising strategy for the veterinary pharmaceutical industry. This study was designed with the intent to produce and study the kinetics of release of progesterone (P4) encapsulated in nanoparticles of biodegradable polymers produced using supercritical (SAS). Particles of Poly-hydroxy-butyrate and valerate (PHB-V) of three different sizes (groups V1-PHB, PHB-PHB-V2 and V3) and their combination with poly-e-caprolactano (PCL; groups PHB-V1/PCL , and PHB-V2/PCL PHB-V3/PCL) were impregnated with P4, weighed, suspended in 10 mL of ethanol / water 60:40 (v / v) and placed in a water bath with agitation. In times 2min, 2h, 4h, 8h, 12h, 24h and 48h, samples of 1 mL. After centrifugation (2,000 g for 10 min at 37 ° C) samples were filtered (0.45 mm) and subjected to analysis by LC-MS/MS for the quantification of P4. We used a mass spectrometer tripo-quadrupole API-4000 Q TRAP (Applied Biosystems) equipped with ESI source and Turbo-V. Analyses were performed in MRM mode in positive mode in order to monitor the transitions 315.5> 109.1 and 315.5> 297.2. We used a HPLC Agilent 1100 series isocratic conditions for the analyte in methanol / water 50% in total running time of 2.5 min. The calibration curve was constructed with triplicates of one, five, 10, 25 and 50 ng / ml of P4. Statistical analysis included ANOVA and interaction (sizes of PHB-V and the presence / absence of PCL), considering the significance level of 5%. It was observed that the association of PHB-V1/PCL increased the amount of progesterone released in relation to PHB-V1 isolate. The same effect was observed for the group PHB-V3/PCL. However, the association PHB-V2/PCL led to a decrease in the release of progesterone in relation to isolated PHB-V2. The release kinetics differed between groups in different time periods studied. Thus, the results show that differences in size of nanoparticles of PHB-V and its associations with the PCL can affect the quantity and the kinetics of drug release in vitro release using solvent alcohol and water. The use of super critical means for producing particles, provided a greater burden of P4 and alters the release kinetics.

Poli-hidroxialcanoatos (PHA) são poliésteres naturais, acumulados por muitas bactérias sob condições de estresse nutricional, que atuam como reserva de carbono e energia. No Brasil, o bagaço de cana-de-açúcar é um importante resíduo lignocelulósico que ainda contém açúcares, podendo servir como precursores de outros produtos como os PHA. Em mistura de açúcares, diversas bactérias consomem preferencialmente a glicose depois os outros açúcares. Esta resposta é denominada repressão catabólica (RC). Neste trabalho foram estudadas estratégias pra reduzir o processo de RC, para que os açúcares em mistura sejam consumidos simultaneamente e inserir genes que permitam a síntese de polihidroxialcanoatos (PHA) em E. coli VH33 e W3110. O meio M9 sem suplementação foi selecionado e foi utilizado em ensaio de acúmulo em biorreator. Neste ensaio a linhagem mutante VH33 pSK-::phaCABCn chegou a acumular um pouco mais de 27% de sua biomassa seca em forma de PHA. Ao fazer a análise de fluxos metabólicos foi observado que a linhagem já estava em sua capacidade máxima teórica. Nestes ensaios a repressão catabólica ainda estava presente. Foram realizados ensaios em biorreator com hidrolisado do bagaço de cana- de- açúcar, porém a bactéria não foi capaz de crescer. / Polyhydroxyalkanoates (PHA) are natural polyesters accumulated by many bacteria under nutritional stress conditions; with the role of as carbon and energy sources. In Brazil, the sugarcane bagasse is an important lignocellulosic crop that can be used as precursors for other products, for instance, PHAs. E. coli are capable to select, in a mixture of sources of carbon, that promotes the best bacterial growth rate. This phenomenon is known as catabolite repression (CR). The aim of this work is to create strategies to reduce the repression catabolite process. During this project, sugar mixtures have been simultaneously consumed. Genes were inserted in E. coli VH33 and the wild type W3110. The M9 medium without supplementation was selected and used to accumulate bioreactor assay. The mutant strain VH33 pSK-::phaCABCn accumulated up to 27% of PHA. In the metabolic flux analysis, it was observed that LFM 862 strain was already in the theoretical maximum capacity. The catabolic repression was practically abolished in this assay. Bioreactor assays were made using sugarcane hydrolysate, but the strain was not capable to grow.

Abstract Lignins have polyphenolic structures, making them candidates to replace phenols and polyphenols in polymers. Lignins are highly recalcitrant, making their refining challenging, requiring harsh temperatures and pressures. Lignins could be partially modified under milder conditions for their use in biopolymers. The main purpose of this research was to upgrade Indulin AT, a kraft pine lignin, to enhance its properties. The first part of this thesis dealt with formic acid aided pressurized hot water extraction (FAPHWE) of hemicelluloses from birch hardwood as the first step in separating the components of a lignocellulosic feedstock (LCF). More than half of the hemicelluloses were extracted as hydrolysis products, while keeping the cellulose hydrolysis products in the extract under 5% and the lignin under 3%. In the second part of this work, a method to determine the amount of phenolic hydroxyl groups (OHph) in lignins was assessed. The Δε IDUS method was found to be useful for comparing the OHph of pine kraft and birch milox lignins, albeit not as precise as carbon-13 nuclear magnetic resonance spectroscopy (13C-NMR). The third part of this thesis explored the tuning of the molar mass (MM) and OHph of Indulin AT by aqueous ethanol fractionation. The results showed that a higher water content favored the extraction of fractions with low MM and low OHph. A high ethanol content favored the extraction of fractions with medium MM and high OHph. A 50–60 wt% ethanol content allowed for near complete solubilization of Indulin AT, which could be beneficial for a single-phase chemical reaction. The fourth part of this research dealt with the depolymerization of Indulin AT in an ethanol-water solvent with formic acid as hydrogen donor. The properties of interest were MM, polydispersity (PDI), OHph, and formaldehyde uptake capability (FUC). The results of the reaction were affected predominantly by temperature. Higher temperatures led to lower MM and PDI, and higher OHph and FUC. The results of this thesis suggest that, in a biorefinery, the first step before delignification of an LCF could be FAPHWE. It was found that the properties of Indulin AT (OHph, FUC, and MM) could be enhanced by chemical depolymerization and physical fractionation. Modified lignins with higher OHph and FUC could be utilized in biopolymer applications such as phenolic resins and polyurethanes. / Tiivistelmä Ligniini on rakenteeltaan polyfenoli, mikä tekee siitä mahdollisen fenolien korvaajan polyfenolien valmistuksessa. Ligniinin rakenne on hyvin kestävä, mikä tekee sen jalostuksesta haastavaa vaatien usein korkean lämpötilan ja paineen käyttöä. Tästä huolimatta ligniiniä voidaan tietyssä määrin muokata miedommissa olosuhteissa, mikä lisää sen käyttökelpoisuutta biopolymeerien raaka-aineena. Tämän tutkimuksen tarkoitus oli jalostaa Indulin AT -kraft ligniiniä siten, että sen ominaisuudet paranevat. Aluksi väitöstyössä tarkasteltiin puun hemiselluloosan muurahaishappokatalysoidun kuumavesiuutton soveltuvuutta lignoselluloosaraaka-aineiden fraktioinnin ensimmäiseksi vaiheeksi. Yli puolet hemiselluloosasta voitiin uuttaa monosakkarideiksi samalla, kun selluloosasta uuttui alle 5 % ja ligniinistä alle 3 %. Seuraavaksi arvioitiin fenolisten hydroksyyliryhmien määritysmenetelmää. Δε IDUS metodin havaittiin olevan hyödyllinen ainakin sulfaattimenetelmän havupuuligniinien ja Milox-prosessin koivuligniininäytteiden vertailussa, vaikkakaan se ei ole yhtä tarkka kuin ydinmagneettiseen resonanssispektroskopiaan (NMR) perustuva analyysi. Tämän jälkeen tutkittiin mahdollisuuksia tuottaa etanoli-vesiliuosfraktioinnilla jakeita, joissa ligniinillä on haluttu molekyylikoko ja fenolisten hydroksyyliryhmien pitoisuus. Tulokset näyttivät, että korkea vesipitoisuus suosii pienen molekyylikoon ja matalan OHph -pitoisuuden sisältäviä jakeiden uuttumista. Korkea etanolipitoisuus suosii keskikokoisen molekyylikoon jaetta, jossa ligniinillä on korkea OHph -pitoisuus. 50–60 m-% etanolipitoisuudessa Indulin AT liukenee lähes täydellisesti, mikä voi olla edullista kemiallisten reaktioiden toteuttamiseen yhdessä faasissa. Lopuksi tutkimuksessa tarkasteltiin ligniinin osittaista depolymerisointia etanoli-vesiliottimessa muurahaishapon toimiessa vetylähteenä. Tarkasteltavat tuotteen ominaisuudet olivat molekyylikoko, polydispersiteetti, fenolisten hydroksyyliryhmien määrä ja formaldehydin sitomiskapasiteetti. Lämpötilan havaittiin olevan merkittävin depolymerisointireaktioon vaikuttava tekijä. Korkea lämpötila johtaa pienempään molekyylikokoon ja kapeampaan molekyylikokojakaumaan sekä suurempaan hydroksyyliryhmien määrään ja formaldehydin sitomiskykyyn. Tämän työn tulokset viittaavat siihen, että hemiselluloosan vesiuutto happamissa olosuhteissa voi olla biojalostamon ensimmäinen vaihe, ennen delignifiointia. Lisäksi havaittiin, että ligniinin ominaisuuksia voidaan muokata kemiallisella depolymerisoinnilla ja fysikaalisella fraktioinnilla. Korkeamman hydroksyyliryhmäpitoisuuden ja formaldehydin sitomiskyvyn muokattuja ligniinejä voidaan hyödyntää biopolymeerisovellutuksissa, kuten fenolisissa hartseissa ja polyuretaaneissa.

A torta de mamona é um resíduo gerado da extração de óleo da mamona, que tem potencial para matéria prima para a produção de filmes biodegradáveis. Filmes a base de proteínas têm limitações mecânica. Assim, as propriedades físicas destes materiais biodegradáveis podem ser melhoradas com o uso de agentes químicos, como reticulantes, e de fibras vegetais, como material de reforço. Neste sentido, o objetivo geral desta dissertação foi o desenvolvimento de filmes biodegradáveis à base de proteína extraída da torta da mamona, modificada com glioxal, e reforçados com fibras da polpa de celulose, para emprego na agricultura. Os objetivos específicos foram a avaliação das fibras de celulose em relação ao ganho de umidade, microscopia e estrutura química, e a avaliação do efeito da concentração de fibras sobre as propriedades mecânicas (tração e perfuração), cor, opacidade, brilho, umidade, solubilidade, permeabilidade ao vapor de água, microestrutura, propriedades térmicas, e estrutura química através de espectroscopia de infravermelho com transformada de Fourier. As proteínas foram extraídas da torta de mamona em um reator com controle digital de temperatura (50 ºC), de pH (12, com NaOH) e de agitação (400 rpm), com capacidade para 5 Litros. As fibras de celulose foram dispersas em água com agitador de alta rotação. Os filmes foram preparados por desidratação de soluções formadoras de filmes (SFF) com 6g de proteína/100 g de SFF, 5g glioxal/100g de proteína, 30 g de glicerol/100 g de proteína e 0; 2,5; 5; 7,5; 10 e 12,5g de fibras/100 g de proteína. A adição de fibras não mostrou efeito sobre a espessura, umidade, solubilidade em água e permeabilidade ao vapor de água dos filmes. Entretanto, as propriedades mecânicas do material melhoraram em função da concentração de fibras. O acréscimo de fibra provocou aumento na força de perfuração, tensão na ruptura e módulo de elasticidade e diminuição na deformação dos filmes. A adição de fibras também exerceu efeito sobre a cor, opacidade e brilho dos compósitos. Os resultados das análises por microscopia eletrônica de varredura permitiu verificar que as fibras de celulose estavam bem dispersas na matriz do filme, explicando seu efeito sobre as propriedades mecânicas dos filmes. E, as análises por espectroscopia de infravermelho com transformada de Fourier corroboraram com esses resultados. O reforço com fibras mostrou-se eficiente e uma excelente alternativa para a produção de filmes a base de biopolímeros. / Castor bean (Ricinus communis L.) cake is a by product of the extraction process of castor oil, which has potential for biodegradable films production. Proteins-based films have mechanical limitations; however it physical properties can be improved with the use of chemical agents, as cross linker, and of vegetal fibers, as reinforcement load. Therefore, the aim of this work was the development of films based on proteins extracted from castor bean (Ricinus communis L.) cake crosslinked with glyoxal and reinforced with cellulose pulp fibers, to be used in agriculture. More specifically, the objectives of this work were the evaluation of cellulose fibers, moisture gain, microstructure and chemical structure, and the evaluation of the effect of fiber content on thickness, moisture content, mechanical properties (by tensile and puncture tests), color, opacity, gloss, solubility in water, water vapor permeability, color, opacity, gloss, microstructure by scanning electron microscopy, and chemical structure by Fourier transform infrared spectroscopy. Proteins were extracted from castor beans cake in a reactor with digital temperature control (50ºC), pH (12, with NaOH) and agitation (400 rpm) with 5L capacity. Cellulose fibers were dispersed in water using a high shear stirrer. Films were prepared by dehydration of film-forming solutions (FFS) with 6g protein/100g FFS, 5g glyoxal/100g protein, 30g glycerol/100g protein and 0; 2.5; 5; 7.5; 10 and 12.5g cellulose fibers/100g protein. Fibers content had no effect on thickness, moisture content, solubility in water and water vapor permeability of films. Nevertheless, the mechanical properties of films were improved as a function of fiber concentration. The increasing in fibers concentration increased puncture force, tensile strength and elastic modulus and decreased films deformation. The addition of fibers also had an effect on color, opacity and gloss of composites. The results of scanning electron microscopy showed that cellulose fibers were well dispersed in the film matrix, explaining their effect on mechanical properties of films. Additionally, analysis by Fourier transform infrared spectroscopy corroborated with these results. Fiber reinforcement was effective and seems to be a great alternative for the production of films based on biopolymers.

Made available in DSpace on 2017-07-10T15:14:40Z (GMT). No. of bitstreams: 1 Karine_N_Lupatini.pdf: 2653837 bytes, checksum: 3f96563a78bfc1de4ba5e308ad1fe38b (MD5) Previous issue date: 2016-03-22 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / The biopolymer Chitosan has become object of several studies in recent years as proton conductive polymer membrane of hydrogen into PEM fuel cells. The main reasons are related to the possibility to undergo chemical and physical changes due to amine groups present, and its low cost. The schoolwork testing Chitosan membranes as proton conductivity, generally employ arrays of other polymers together, forming composites with properties better suited for this purpose. Very few schoolwork bother to study the effect of the properties of chitosan on the obtaining of these membranes, and Chitosan membranes are usually employed. The aim of this project was to develop membranes of Chitosan from shrimp shell of fresh water produced in Western Paraná, to be used as electrolyte fuel cells and comparing the results with those presented by the use of commercial Chitosan sample. This schoolwork investigated the influence of degree of deacetylation (GD), molar mass and reticulation of the different samples of chitosan on the performance of the membranes obtained front proton conductivity, water absorption, ion exchange capacity, mechanical strength, XRD and TGA. Chitosan QB, produced in the laboratory, presented desired characteristics of 76% GD and molar mass of 64 kDA. These properties have improved the performance of Chitosan membranes, as well as the crosslinking. The FTIR analysis proved that the crosslinking did not alter the functional groups of Chitosan, while the DRX found that the character of the MQBs became more amorphous than the MQAs and, in general, by the dTG says that the membranes have thermal stability up to 600-700° C, suitable to be applied in CaC. MQB04 and MQB05 membranes resulted in higher conductivity of 1.9 and 1.6 x 10-2 respectively and, in this case, the crosslinking provided better mechanical resistance of up to 45 N to the MQB04 membrane. The protonic conductivity obtained for MQB04 and MQB05 was significant, but still low compared to Nafion®. However, the versatility of Chitosan and the possibility of exploration and chemical modifications of its structure, still making it attractive for the research and development of Proton conducting polymeric membranes with superior performance to found in this schoolwork / O biopolímero quitosana tem se tornado objeto de vários estudos nos últimos anos como membrana polimérica condutora de prótons de hidrogênio em células a combustível do tipo PEM. As principais razões estão relacionadas à possibilidade de sofrer modificações físicas e químicas devido aos grupos amina presentes, e a seu baixo custo. Os trabalhos que testam membranas de quitosana como condutoras de prótons, geralmente empregam matrizes de outros polímeros em conjunto, formando compósitos com propriedades mais adequadas para esta finalidade. Pouquíssimos trabalhos se preocupam em estudar o efeito das propriedades da quitosana sobre a obtenção destas membranas, sendo que normalmente membranas de quitosana comercial são empregadas. O objetivo do presente trabalho foi desenvolver membranas de quitosana extraída de carapaças de camarão de água doce produzidos na região oeste do Paraná, para serem empregadas como eletrólito em células a combustível, comparando os resultados obtidos com aqueles apresentados pelo uso de amostra de quitosana comercial. Este trabalho investigou a influência do grau de desacetilação (GD), massa molar e reticulação das distintas amostras de quitosana, sobre o desempenho das membranas obtidas frente à condutividade protônica, absorção de água, capacidade de troca iônica, resistência mecânica, DRX e TGA. A quitosana QB, produzida no laboratório, apresentou características desejadas de GD de 76% e massa molar de 64 kDA. As propriedades de QB melhoraram o desempenho das membranas de quitosana, assim como a reticulação. A análise de FTIR comprovou que a reticulação não alterou os grupos funcionais da quitosana, enquanto que a DRX constatou que o caráter das MQBs tornou-se mais amorfo que às MQAs. As membranas MQB04 e MQB05 resultaram em condutividades superiores de 1,9 e 1,6x10-2 respectivamente e, neste caso, a reticulação proporcionou melhor resistência mecânica de até 45 N para a membrana MQB04. A condutividade protônica obtida para MQB04 e MQB05 foi expressiva, porém, ainda baixa se comparada ao Nafion®. Entretanto, a versatilidade da quitosana e a possibilidade de exploração e de modificações químicas da sua estrutura, continua tornando-a atrativa para a pesquisa e desenvolvimento de membranas poliméricas condutoras de prótons com desempenho ainda superior aos encontrados neste trabalho

Os polihidroxialcanoatos (PHA) são poliésteres bacterianos. Na sua biossíntese, a PHA sintase incorpora monômeros 3HA à cadeia polimérica. O objetivo deste trabalho foi estudar o potencial da PHA sintase de 2 isolados do gênero Burkholderia sp. na produção de copolímeros. Construiram-se linhagens recombinantes que abrigavam os genes da PHA sintase classe I, em mutantes de Pseudomonas sp. e Burkholderia sacchari, que não acumulam PHA. Foram realizados ensaios de acúmulo de PHA usando glicose como fonte de carbono, apresentando a produção de unidades de 3HB, 3HO e 3HD nas linhagens recombinantes de Pseudomonas sp. As linhagens recombinantes de B. sacchari incorporaram como único constituinte P(3HB). Ensaios de acúmulo de PHA foram realizados nas linhagens recombinantes de B. sacchari, usando como co-substratos diferentes ácidos graxos, sendo detectada a incorporação de unidades de 3HV e 3HHx além do 3HB, quando foram fornecidos acido hexanóico e valérico. Estes resultados indicam que as PHA sintases classe I são capazes de incorporar diferentes unidades monoméricas. / The polyhydroxyalkanoates (PHA) are bacterial polyester. In their biosynthesis, the PHA synthase incorporates monomers 3HA to the polymer chain. The objective of this work was to study the potential of PHA synthase of 2 isolates of the genus Burkholderia sp. in the production of copolymers. Were constructed recombinant strains that housed the genes of PHA synthase class I mutants of Pseudomonas sp. and Burkholderia sacchari, which do not accumulate PHA. PHA accumulation assays were performed using glucose as carbon source, showing the production of units of 3HB, 3HO and 3HD in recombinant strains of Pseudomonas sp. The recombinant strains of B. sacchari incorporated as single constituent P(3HB). PHA accumulation assays were performed on the recombinant strains of B. sacchari, Using as co-substrates different fatty acids, being detected the incorporation of units of 3HV and 3HHx beyond the 3HB, when were supplied hexanoic acid and valerico. These results indicate that the PHA synthases class I are able to incorporate different monomer units.

Thesis (Ph. D.)--Ohio State University, 2006. / Full text release at OhioLINK's ETD Center delayed at author's request

The growing incidences of coronary artery bypass graft surgeries have triggered a need to engineer a viable small diameter blood vessel substitute. An ideal tissue engineered vascular graft should mimic the microenvironment of a native blood vessel, while providing the adequate compliance post-implantation. Current vascular graft technologies lack the ability to promote vascular ECM deposition, leading to a compliance mismatch and ultimately, graft failure. Hence, in order to engineer suitable vascular grafts, this thesis describes the synthesis and characterization of novel elastin mimetic peptides, EM-19 and EM-23, capable of promoting vascular ECM deposition within a poly(ethylene glycol) diacrylate (PEG-DA) hydrogel. By combining the material properties of a synthetic and bio-inspired polymer, a suitable microenvironment for cell growth and ECM deposition can be engineered, leading to improved compliance. As such, characterization of EM-19 and EM-23 was conducted in human vascular smooth muscle cell (SMC) cultures, and the peptides self-assembled with a growing elastic matrix. After grafting the peptides onto the surface of PEG-DA hydrogels, EM-23 increased SMC adhesion by 6000% over PEG-RGDS hydrogels, which have been the gold standard of cell adhesive PEG scaffolds. Moreover, EM-23 grafted surfaces were able to promote elastin deposition that was comparable to tissue cultured polystyrene (TCPS) surface even though TCPS had roughly 4.5 times more SMCs adhered. Once translated to a 3D model, EM-23 also stimulated increased elastin deposition and improved the mechanical strength of the scaffold over time. Moreover, degradation studies suggested that EM-23 may serve as a template that not only promotes ECM deposition, but also allows ECM remodeling over time. The characterization studies in this thesis suggest that this peptide is an extremely promising candidate for improving vascular ECM deposition within a synthetic substrate, and that it may be beneficial to incorporate EM-23 within polymeric scaffolds to engineer compliant vascular grafts.

Graduation date: 1992

This thesis describes the development of microfluidic (MF) platforms for the study of biological and chemical processes. In particular the thesis is divided into two distinct parts: (i) development of a MF methodology to generate tunable cell-laden microenvironments for detailed studies of cell behavior, and (ii) the design and fabrication of MF reactors for studies of chemical reactions. First, this thesis presented the generation of biopolymer microenvironments for cell studies. In the first project we demonstrated a high-throughput MF system for generating cell-laden agarose microgels with a controllable ratio of two different types of cells. The MF co-encapsulation system was shown to be a robust method for identifying autocrine and/or paracrine dependence of specific cell subpopulations. In the second project we studied the effect of the mechanical properties on the behavior of acute myeloid leukemia (AML2) cancer cells. Cell-laden macroscopic agarose gels were prepared at varying agarose concentrations. A modest range of the elastic modulus of the agarose gels were achieved, ranging from 0.62 kPa to 20.21 kPa at room temperature. We observed a pronounced decrease in cell proliferation in stiffer gels when compared to the gels with lower elastic moduli. The second part of the thesis focuses on the development of MF platforms for studying chemical reactions. In the third project presented in this thesis, we exploited the temperature dependent solubility of CO2 in order to: (i) study the temperature mediated CO2 transfer between the gas and the various liquid phases on short time scales, and (ii) to generate bubbles with a dense layer of colloid particles (armoured bubbles). The fourth project involved the fabrication of a multi-modal MF device with integrated analytical probes. The MF device comprised a pH, temperature, and ATR-FTIR probes for in-situ analysis of chemical reactions in real-time. Furthermore, the MF reactor featured a temperature controlled feedback system capable of maintaining on-chip temperatures at flow rates up to 50 mL/hr.