Orientadores: Cecília Amélia de Carvalho Zavaglia, Ana Beatriz Albino Almeida / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia Mecânica / Made available in DSpace on 2018-08-18T02:56:18Z (GMT). No. of bitstreams: 1 Feliciano_DanielleFerreira_M.pdf: 2215803 bytes, checksum: 78c936869613a6b313b028d4e7b84078 (MD5) Previous issue date: 2011 / Resumo: Defeitos, doenças e acidentes que acometem a cartilagem articular para suportar às constantes solicitações mecânicas que estas regiões estão sujeitas, sendo indicada a utilização de estruturas viscoelástica resistente alto grau de atrito para preencher tais defeitos. Desta forma, foi selecionado o uso de hidrogéis para esta aplicação específica. Hidrogéis a base de poli(álcool vinilico) (PVAl) e polietileno glicol (PEG) apresentam propriedades mais adequadas, como biocompatibilidade, não estimulando reação imunológica ao organismo; baixa adesão de células sanguíneas, evitando coágulos; capacidade de absorção de água (intumecimento), proporcionando lubrificação do material e alto grau de transparência. O processo para obtenção desta blenda e formação de hidrogel foi realizado utilizando uma proporção de 1:9 (PEG:PVAl). O iniciador 2- hidroxi-4'-(2-hidroxietoxi)-2-metilpropiofenona foi adicionado à blenda, em 1% do volume total. È este iniciador, quando estimulado via temperatura, laser ou infravermelho, que irá desencadear as ligações intermacromoleculares de PEG-PVAl permitindo a formação de uma organização grafitizada da blenda dentro do hidrogel. Foi acompanhada a cinética de formação deste hidrogel através de reometria de placas, Espectroscopia de Infravermelho por Transformada de Fourier (FTIR) e Calorimetria Diferencial de Varredura (DSC). As amostras também foram devidamente caracterizadas quanto à condutividade térmica, densidade e absorção óptica. Observou-se que o iniciador ativou as ligações do grupo acetato do PVAl com as hidroxilas do PEG, resultando em formação de grupos ester. São estas ligações que caracterizam a formação do hidrogel grafitizado. Além disso, ocorreu a inversão do módulo viscoso em relação ao módulo de elasticidade, comprovando a reação de grafitização / Abstract: Defects, diseases and accidents that affect the articular cartilage can withstand constant mechanical stresses that they are subject, which indicated the use of viscoelastic structures resistant to high friction to fill these defects. In this way, the use was selected of hydrogels for this application it specifies. To base of I polished hydrogels polyvinyl alcohol (PVA) and polyethylene glycol (PEG) present more appropriate properties, biocompatibility, not stimulating reaction immunologically to the organism; low adhesion of blood cells, avoiding clots; capacity of absorption of water (swelling), providing lubrication of the material and high degree of transparency. The process for getting this blend and formation of hydrogel was carried out using a proportion of 1:9 (PEG:PVA). The initiator hidroxi 2-hidroxi-4 '-(2-hidroxietoxi)-2- metilpropiofenona was added to the blend, in 1 % of the total volume. This initiator, when stimulated he was seeing temperature, laser or infrared, what will be going to unleash the connections intermacromoleculares of PEG-PVA allowing the formation of an grafiting organization of the blend inside the hydrogel. There was accompanied the kinetic one of formation of this hydrogel through parallel plates rheometry, Fourier transform infrared spectroscopy (FTIR) and Differential scanning calorimetry (DSC). The samples also were characterized property as for the thermal condutivity, density and optical absorption. It noticed to itself that the initiator activated the connections of the group acetate of the PVA with the hydroxyl group of PEG, when ester is turning in formation of groups. It is these connections that characterize the formation of the hydrogel grafiting. Besides, it took place to inversion of the viscous module regarding the module of elasticity, proving the reaction of grafiting / Mestrado / Materiais e Processos de Fabricação / Mestre em Engenharia Mecânica

Orientador: Francisco Benedito Teixeira Pessine / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Química / Made available in DSpace on 2018-08-24T01:26:17Z (GMT). No. of bitstreams: 1 Marques_LeticiaPaifer_M.pdf: 4333961 bytes, checksum: dd287508ba192ad95556c2094f8d9d2a (MD5) Previous issue date: 2013 / Resumo: Através de modificações na estrutura química da molécula de pectina cítrica, polissacarídeo utilizado nas indústrias alimentícias como agente gelificante/espessante, foi desenvolvido um Sistema Depot para entrega subcutânea de nanopartículas lipídicas sólidas (NLS) e carreadores lipídicos nanoestruturados (CLN) contendo, respectivamente, Dexametasona (DXM) e Valerato de Betametasona (BTM). Os fármacos foram encapsulados nesses sistemas devido à necessidade de modificar seus perfis de liberação, diminuindo o número de aplicações e sua dosagem, reduzindo ocorrência de efeitos adversos. O produto da reação de oxidação da pectina cítrica foi caracterizado através de Espectroscopia da região do Infravermelho, Análise Termogravimétrica e Calorimetria Diferencial de Varredura. Os resultados indicaram o sucesso da reação, confirmado através da gelificação do hidrogel de pectina cítrica oxidada. As NLS e os CLN apresentaram valores de diâmetro médio em torno de 80nm, alta eficiência de encapsulação e perfis de liberação prolongada; para os CLN o fármaco BTM foi liberado ao longo de 144 horas e para as NLS o fármaco DXM foi liberado ao longo de 24 horas. Estes resultados mostram que as NLS de DXM poderiam ser utilizadas para tratar processos inflamatórios agudos e que os CLN de BTM seriam úteis no tratamento de processos inflamatórios crônicos / Abstract: A modified chemical structure of citrus pectin was used to develop a Depot system for subcutaneuous delivery of solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) containing, respectively, Dexamethasone (DXM) and Betamethasone Valerate (BTM). Citrus pectin is a polysaccharide used in food industry as a gelling/thickener agent. The drugs were encapsulated in this system with the aim to modify their release profiles. This would result in the reduction of the number of applications and dosage. As a consequence, it would also reduce adverse side effects that these drugs may cause. The citrus pectin oxidation product was characterized by Infrared Spectroscopy, Thermogravimetric Analysis and Differential Scanning Calorimetry. The results indicated that the reaction occurred. This was confirmed by gelation of the citrus pectin oxidation product. SLN and CLN showed values with diameters around 80nm, high encapsulation efficiency and sustained release profiles. BTM was released from the CLN over 144 hours and DXM was released from the NLS over 24 hours. These results showed that the DXM-NLS would be useful in the treatment of acute inflammatory processes. BTM-CLN could be applied in the treatment of chronic inflammatory processes / Mestrado / Físico-Química / Mestra em Química

Dynamic covalent chemistry (DCC) is currently exploited in several areas of biomedical applications such as in drug discovery, sensing, molecular separation, catalysis etc. Hydrazone and oxime chemistry have several advantages, such as mild reaction conditions, selectivity, efficiency, and biocompatibility and therefore, have the potential to be for bioconjugation applications. However, these reactions suffer from major drawbacks of slow reaction rate and poor bond stability under physiological conditions. In this regard, the work presented in this thesis focuses on designing novel bioconjugation reactions amenable under physiological conditions with tunable reaction kinetics and conjugation stability. The first part of the thesis presents different strategies of dynamic covalent reactions utilized for biomedical applications. In the next part, a detailed study related to the mechanism and catalysis of oxime chemistry was investigated in the presence of various catalysts. Aniline, carboxylate and saline were selective as target catalysts and their reaction kinetics were compared under physiological conditions (Paper I and II). Then we attempted to explore the potential of those chemistries in fabricating 3D hydrogel scaffolds for regenerative medicine application. A novel mild and regioselective method was devised to introduce an aldehyde moiety onto glycosaminoglycans structure. This involved the introduction of amino glycerol to glycosaminoglycans, followed by regioselective oxidation of tailed flexible diol without affecting the C2-C3 diol groups on the disaccharide repeating unit. The oxidation rate of the tailed flexible diol was 4-times faster than that of C2-C3 diol groups of native glycosaminoglycan. This strategy preserves the structural integrity of the glycosaminoglycans and provides a functional aldehyde moiety (Paper III). Further, different types of hydrazones were designed and their hydrolytic stability under acidic condition was carefully evaluated. The hydrazone linkage with the highest hydrolytic stability was utilized in the preparation of extracellular matrix hydrogel for delivery of bone morphogenetic proteins 2 in bone regeneration (Paper IV) and studied for controlled release of the growth factor (Paper III). In summary, this thesis presents a selection of strategies for designing bioconjugation chemistries that possess tunable stability and reaction kinetics under physiological conditions. These chemistries are powerful tools for conjugation of biomolecules for the biomedical applications.

Die Funktionalisierung von tetra-PEG Makromolekülen mit fotoreaktiven Gruppen und die anschließende Umsetzung zu Hydrogelen durch fotochemische Vernetzung werden beschrieben. Die Funktionalisierung der Makromoleküle wird mittels UV-Vis- und NMR-Spektroskopie nachgewiesen, während der Verlauf der Vernetzung über die dynamische Lichtstreuung und IR-Spektroskopie betrachtet wird. Die hergestellten Hydrogele werden hinsichtlich des Sol-Anteils und der Quelleigenschaften untersucht. Über den Umsatz wird die Konzentration der Netzketten theoretisch berechnet. Einen weiteren Schwerpunkt bildet die Charakterisierung der Hydrogele hinsichtlich der mechanischen Eigenschaften. Über den Speichermodul wird die Konzentration der Netzketten experimentell bestimmt. Mittels dynamischer Lichtstreuung werden die kooperativen Diffusionskoeffizienten und Maschenweiten der Hydrogele bestimmt.

This thesis presents work on investigations into the mechanical properties of connective tissue. A model system of hydrogels was used to investigate how volume change through water flow is coupled to relaxation. This was done using digital image correlation (DIC) and a custom built setup. It was found, in hydrogels, that water loss is directly coupled to an increase in tension and water intake is directly coupled to tension relaxation. The experimental setup was tested by investigating the mechanical properties of the well known material polydimethylsiloxane (PDMS) and the novel materials of carbon nanotube (CNT) elastomers, cholesteric liquid crystal elastomers (CLCEs), and 3D polydomain liquid crystal elastomers (3DLCEs). The setup accurately demonstrated the incompressibility of PDMS, even at short time scales, and demonstrated how DIC can map the inhomogeneity of material by locating clusters of CNTs in CNT elastomers by how they deform. Novel results for 3DLCEs were also found, where it was discovered that there is a softening of the bulk modulus at small time scales resulting in a volume increase following deformation, the bulk modulus then recovers and there is over all no volume change. This is in stark contrast to the typical case, where it is the shear modulus that becomes comparable to the bulk modulus, resulting in increased volume. A theoretical investigation was carried out into critical damping in viscoelastic oscillators, where the aim was to apply to the findings to connective tissue. The fractional Maxwell model and zener model where both solved for, where it was found that damping decreases as the material becomes more solid and the peak of critical damping becomes broader. Finally, investigations into how strain relates to the viscoelastic properties of connective tissue were carried out on horse tendon and rat fascia. How relaxation changes was determined through the relaxation constant, where a large constant means it takes the sample longer to relax and it is more solid like. It was found, that in general, the relaxation constant increases quickly with an imposed strain and then either stabilises or increases more slowly. This growth of relaxation constant also occurs during the initial stages of tissue injury, where irreversible deformation occurs.

Chronic wounds are a major financial and clinical burden causing the deaths of millions per year. Over expression of elastase is well documented as the main culprit that delays the normal wound repair process within chronic wounds. The aim of this thesis is to design a responsive chronic wound dressing based on the hydrogel polymer, PEGA (polyethylene glycol acrylamide) in the form of particles to mop-up excess elastase by exploiting polymer collapse in response to elastase hydrolytic activity within sample fluids mimicking the environment of chronic wounds. PEGA particles were functionalised with enzyme cleavable peptides (ECPs) containing charged residues. Upon cleavage the charge balance changes, causing polymer swelling and consequent elastase entrapment. The pH range of chronic wounds is reported in the range of 5.45 - 8.65. Due to its pI which is around 8.3, within this range elastase exist both in its cationic and anionic forms. To accommodate a hydrogel dressing that could selectively entrap excess elastase both in its cationic and anionic, oppositely charged ECPs were designed. In its cationic form, elastase was found to have a high preference of cleaving ECPs and penetrating into PEGA particles bearing negative charges. In contrast, in its anionic form the opposite effect was observed, wherein elastase preferred to cleave ECPs and penetrate PEGA particles bearing positive charges. The diffusion, accessibility and entrapment of elastase into functionalised PEGA particles was explored using various fluorescence microscopy techniques. Removal of the charged residue by elastase showed a reduction in particle swelling causing the pores of PEGA particles to become restricted. In this manner, cleaved PEGA particles prevented the accessibility of molecules with a molecular weight as low as 20 kDa into the cleaved PEGA particles. Since elastase has a molecular weight of 25.9 kDa the collapsing of the pores within PEGA particles entrapped elastase inside the interior of cleaved PEGA particles. In its cationic form (at pH 7.4) elastase was found to penetrate and become trapped more into both negative and positive PEGA particles compared to neutral particles. The negative particles were shown to trapped cationic elastase within 2 minutes compared to the positive particles. In contrast, the neutral particles failed to retain and encapsulate elastase as the fluorescence inside the neutral particles was found to decrease. Coinciding with these observations, after sample fluids containing elastase were treated with functionalised PEGA particles, the residual elastase activity in sample fluids was reduced more by the charged PEGA particles compared to neutral particles. The cell culture studies demonstrated that the elastase activity observed in human dermal fibroblasts (HDF) was also reduced more by the charged particles compared to the neutral particles. However, the positive particles were found to significantly reduced HDF-elastase activity compared to both the negative and neutral PEGA particles. Overall, this thesis exemplifies that on the basis of charge selective cleaving of ECPs coupled to PEGA particles can be exploited to selectively remove excess proteases such as elastase from sample fluids mimicking the environment of chronic wounds.

Desde o início da espécie humana, houve quem procurasse auxiliar o corpo na tentativa natural de restaurar suas partes injuriadas. Um dos grandes desafios atuais é a substituição de tecidos do organismo, inclusive em áreas de lesão cutânea. Um biomaterial pode ser utilizado para melhorar, aumentar ou substituir, parcial ou inteiramente tecidos ou órgãos. A membrana de celulose bacteriana (CB) possui moldabilidade, boas propriedades mecânicas, permeabilidade seletiva, permitindo a passagem de vapor d\'água, mas impedindo a passagem de microrganismos. O colágeno (COL) vem sendo amplamente usado como material na fabricação de biomateriais. Neste trabalho obteve-se membrana e hidrogel de CB-COL, caracterizados de diferentes maneiras. Foram realizados, estudos in vivo, análises macroscópica e histológica de coberturas de CB-COL, comparando com os controles (coágulo e a pomada de colagenase), após a aplicação sobre as feridas confeccionadas no dorso de ratos. Os animais foram sacrificados depois de 3, 7, 15 e 30 dias, e os dorsos processados segundo rotina histológica para coloração em HE. As caracterizações realizadas neste trabalho (microscopia eletrônica de varredura (MEV), análise termogravimétrica (TG), espectroscopia no infravermelho com transformada de Fourier (FT-IR) e difratometria de raios-X (DRX)) confirmaram a incorporação do COL às matrizes de CB. A avaliação macroscópica somente demonstrou diferença estatisticamente significante da reparação tecidual entre os tratamentos aos sete dias de pós-operatório, sendo que o hidrogel apresentou uma tendência para uma reparação mais rápida. Os resultados da avaliação histológica demonstraram diferença estatisticamente significante para reação inflamatória tecidual entre os tratamentos em todos os períodos estudados. Na avaliação da qualidade, quantidade e orientação das fibras colágenas, somente o período de três dias que não apresentou diferença estatisticamente significante entre os tratamentos. Conclui-se com esses resultados que as duas coberturas são biocompatíveis. / Since the beginning of the human race, there was those who sought to assist the body in a natural attempt to restore yours injured parts. One of the main current challenges is the replacement of body tissues, including areas of skin lesion. A biomaterial can be used to improve, enhance or replace, partially or fully tissues or organs. The membrane of bacterial cellulose (BC) has moldability, good mechanical properties, selective permeability, allowing the passage of water vapor but preventing the passage of microorganisms. The collagen (COL) has been widely used as material in the manufacture of biomaterials. In this study was obtained hydrogel and membrane BC-COL, characterized in different ways. Were realized in vivo studies, macroscopic and histological analyzes from dressings of BC-COL, comparing with controls (clot and collagenase ointment), after applying in wounds on the backs of rats. The animals were sacrificed after 3, 7, 15 and 30 days, and the scars were processed according to histological routine to HE staining. The characterizations performed in this study (scanning electron microscopy (SEM), thermogravimetric analysis (TGA), infrared spectroscopy with Fourier transform (FT-IR) and X-ray diffraction (XRD)) confirmed the incorporation of the COL to matrices BC. The macroscopic evaluation only demonstrated statistically significant difference of tissue repair between treatments at seven days postoperative, and the hydrogel showed a trend for a faster repair. The results of the histological evaluation showed statistically significant difference in inflammatory tissue reaction between treatments in all periods studied. In quality evaluation, quantity and orientation of collagen fibers, only three days period didnt show statistically significant difference between treatments. We conclude from these results that the two dressings are biocompatible.

abstract: Soft materials are matters that can easily deform from their original shapes and structures under thermal or mechanical stresses, and they range across various groups of materials including liquids, foams, gels, colloids, polymers, and biological substances. Although soft materials already have numerous applications with each of their unique characteristics, integrating materials to achieve complementary functionalities is still a growing need for designing advanced applications of complex requirements. This dissertation explores a unique approach of utilizing intermolecular interactions to accomplish not only the multifunctionality from combined materials but also their tailored properties designed for specific tasks. In this work, multifunctional soft materials are explored in two particular directions, ionic liquids (ILs)-based mixtures and interpenetrating polymer network (IPN). First, ILs-based mixtures were studied to develop liquid electrolytes for molecular electronic transducers (MET) in planetary exploration. For space missions, it is challenging to operate any liquid electrolytes in an extremely low-temperature environment. By tuning intermolecular interactions, the results demonstrated a facile method that has successfully overcome the thermal and transport barriers of ILs-based mixtures at extremely low temperatures. Incorporation of both aqueous and organic solvents in ILs-based electrolyte systems with varying types of intermolecular interactions are investigated, respectively, to yield optimized material properties supporting not only MET sensors but also other electrochemical devices with iodide/triiodide redox couple targeting low temperatures. Second, an environmentally responsive hydrogel was synthesized via interpenetrating two crosslinked polymer networks. The intermolecular interactions facilitated by such an IPN structure enables not only an upper critical solution temperature (UCST) transition but also a mechanical enhancement of the hydrogel. The incorporation of functional units validates a positive swelling response to visible light and also further improves the mechanical properties. This studied IPN system can serve as a promising route in developing “smart” hydrogels utilizing visible light as a simple, inexpensive, and remotely controllable stimulus. Over two directions across from ILs to polymeric networks, this work demonstrates an effective strategy of utilizing intermolecular interactions to not only develop multifunctional soft materials for advanced applications but also discover new properties beyond their original boundaries. / Dissertation/Thesis / Doctoral Dissertation Chemical Engineering 2020

The aim of this master thesis deals with the optimization of the preparation of thin hydrogel films based on polyvinyl alcohol (PVA) with the possibility of incorporating suitable additives (polyelectrolytes, plasticizers, etc.) into the structure of the prepared film to modify its properties. DEAE-Dextran hydrochloride and polyglutamic acid (PGA) were used as polyelectrolytes. The basic characterization of the properties was performed on modified films, which were compared with pure PVA films. The films were characterized by thickness, swelling ability, barrier properties, tensile properties, specific surface area, antimicrobial tests, and thermogravimetric analysis. The swelling ability of PVA/PGA films was very high, which may be a disadvantage for their use in the packaging industry. Swelling increases the amount of water in the matrix of the PVA film, what leads to a higher growth of microorganisms and to degradation of thin film. The water vapor transmission rate was greatly affected by the addition of a plasticizer. The small specific surface area of the films indicates a smooth surface that promotes good barrier properties. Films with the addition of a plasticizer showed relatively good mechanical properties. The values of tensile strength, elongation and elastic modulus were comparable to commercially available films such as polypropylene (PP) or polyethylene (PE). Based on all experiments, PVA, PVA/DEAEDextran films and their variants with the addition of glycerol as a plasticizer were evaluated as the best candidates for the use of these films as packaging materials. The follow-up work could be dealing with the optimization of PVA films for oxygen permeability. Furthermore, the possibilities of using these films in the packaging industry based on the relative humidity of the environment, could be defined as other interesting area of future research.

This diploma thesis is focused on the study of the behaviour of carbon fibers in the hydrogel, especially the viscoelastic modules od these gels ort he coefficient of color transmission through the gel. The main goals were to optimize the samples and measure their viscoelastic modules on a rheometer, in several different modes. This was followed by simulation of physiological conditions for selected samples and their measurement on the rheometer. There was also an experiment of continuous diffusion in cuvettes, in which the penetration of the dye through the gel with the addition of fibers and for comparison also without them. Last but not least diffusion pairs were prepared.