Esta tese apresenta os resultados do estudo de eletrólitos poliméricos protônicos obtidos a base de gelatina e quitosana, modificadas através da adição de glicerol e formaldeído - ácidos acético ou clorídrico foram adicionados para promover a condutividade iônica dos filmes. Foram também preparadas blendas a partir de gelatina com quitosana, assim como filmes a base de gelatina e nanopartículas. Com exceção dos filmes com nanopartículas, todos eles possuem boa transparência, estabilidade térmica, maleabilidade, aderência ao vidro e apresentam uma superfície homogênea, sem trincas ou rachaduras. As temperaturas de transição vítrea (Tg) dos eletrólitos foram obtidas do estreitamento de linha de RMN. A taxa de relaxação spin-rede do \'ANTPOT. 1 H\' em função da temperatura mostrou um máximo bem definido cuja posição depende da concentração de ácido no caso da gelatina e da quantidade de glicerol no caso da quitosana, refletindo a alta mobilidade do próton nestes eletrólitos. As técnicas de RPE, onda contínua e pulsada, foram utilizadas para o estudo de eletrólitos dopados com \'CU\'CL\'O IND.4\'. Os valores de condutividade iônica dos eletrólitos são da ordem de \'10 POT.-5\' S/cm para os filmes de gelatina (com ácido acético ou clorídrico), quitosana e blendas e entre \'10 POT.-6\' a \'10 POT.-8\' para os eletrólitos de gelatina com nanopartículas. Estes estudos revelaram que a concentração de ácido acético ou clorídrico (na gelatina), influencia a condutividade iônica dos eletrólitos, mas, para o caso das blendas esta influência é pequena. No caso dos filmes de gelatina com nanopartículas, a condutividade diminui de forma significativa. Em relação aos eletrólitos de quitosana a condutividade iônica é influenciada pela quantidade de glicerol adicionado. Verificou-se que o aumento da temperatura até 80°C promove o aumento da condutividade iônica para todos os filmes estudados. / This thesis shows the results from the study of protonic polymer electrolytes obtained from gelatin and chitosan, modified by the addition of glycerol and formaldehyde - acetic and hydrochloric acids are added to promote the ionic conductivity of the films. Blends based on chitosan and gelatin were also prepared, as well as films based on gelatin and nanoparticles. With the exception of the films with nanoparticles, all samples presented good transparency, thermal stability, flexibility, adhesion to glass and homogeneous surface without cracks. The glass transition temperature (Tg) of the electrolytes were obtained from the NMR line narrowing. The spin-lattice relaxation rate of the \'ANTPOT. 1 H\' spin-network as a function of temperature showed a well-defined maximum whose position depends on the concentration of acid in the case of gelatin and on the glycerol content in the case of chitosan, reflecting the high mobility of the protons in the electrolytes. Continuous wave and pulsed EPR techniques were used to study the electrolytes doped with \'CU\'CL\'O IND.4\'. The values of the ionic conductivity of the electrolytes are of the order of \'10 POT.-5\' S/cm for the films of gelatin (with acetic or hydrochloric acids), chitosan and blends and from \'10 POT.-6\' to \'10 POT.-8\' for the electrolytes of gelatin with nanoparticles. These studies revealed that the concentration of acetic or hydrochloric acids (in gelatin), influences the ionic conductivity of the electrolytes but, in the case of blends, this influence is small. In the case of the films based on gelatin with nanoparticles, the ionic conductivity decreases significantly. In relation to the electrolyte based on chitosan, the ionic conductivity is influenced by the amount of glycerol added. It was found that increasing the temperature to 80°C promotes the increase of ionic conductivity for all films studied.

Große knöcherne Defekte machen den Einsatz eines Knochenersatzmaterials notwendig. Autogene Spongiosa ist das in jeder Hinsicht unübertroffene Transplantat. Ihre Verfügbarkeit ist jedoch begrenzt. Die Entnahme autogener Spongiosa erfordert meist eine mit zusätzlichen Risiken behaftete und daher zusätzlicher Morbidität verbundene Zweitoperation. Allogene Knochenmatrixgelatine als Weiterverarbeitungsprodukt der demineralisierten Knochenmatrix ist ein osteoinduktives Implantat. Allogene BMG fördert die Regeneration knöcherner Substanzdefekte und kann durch Knochenbanken ständig in ausreichender Menge zur Verfügung gestellt werden. Die verwendete BMG ist ein avitales, vollständig demineralisiertes, antigenfreies Implantat mit günstiger Oberflächenstruktur und guter Bioverträglichkeit. Die Hydroxylapatitkera-mik Endobon® ist eine durch dosierte Verbrennung und Sinterung von boviner Spongiosa hergestellte True Bone Ceramic mit einer organisierten Trabekelstruktur und interkonnek-tierenden Poren. Das Ziel dieser Arbeit war, in vergleichenden Untersuchungen im orthotopen Modell den Einfluß der während der Präparation der BMG herrschenden Temperatur auf die Osteoinduktivität zu erfassen,am Minischwein die knöcherne Regeneration unter dem Einfluß von BMG im Vergleich zur Kombination aus BMG mit der Hydroxylapatitkeramik Endobon® zu untersuchen und dabei gleichzeitigden zeitlichen Verlauf der Knochenbildung beim Heilungsprozeß quantitativ zu erfassen. Die Untersuchung der Temperaturabhängigkeit erfolgte am Trepanationsdefekt bei Wistar- Ratten. Als Negativkontrolle diente der Leerdefekt. Die Heilung des Defekts wurde deskriptiv histologisch und mittels der biochemischen Marker Alkalische Phosphatase, Kalziumgehalt und Hydroxyprolin erfaßt. Die in diesem Versuch verwendete BMG wurde bei 4°C bzw. 22°C hergestellt. Untersuchungszeiträume waren 1, 2, 4, 6 und 12 Wochen. Folgende Ergebnisse wurden erzielt: Beide BMG-Präparationen produzierten eine vollständige Defektheilung nach 12 Wochen.Bei der histologischen Untersuchung konnte zu keinem der Untersuchungszeitpunkte ein Unterschied im Fortschritt der Defektregeneration zwischen beiden Vergleichsgruppen beobachtet werden.Die Aktivität der Alkalischen Phosphatase ist nach der zweiten und der vierten Wochen in der BMG 22°C-Gruppe signifikant (p=0.042 bzw. 0.012) erhöht. Der Kalzium-und Hydroxyprolingehalt werden aus Gründen, die im einzelnen im Kapitel 2.3. diskutiert werden, in diesem Versuch nicht als universell geeignete Parameter zur Erfassung der Osteogenese angesehen. Die Untersuchung der Heilung von Knochendefekten unter dem Einfluß von allogener BMG im Vergleich zu einer Kombination aus BMG mit einer Hydroxylapatitkeramik wurde an Minischweinen durchgeführt. Die zeitliche Dynamik des Knocheneinwuchses wurde anhand histologischer Fluoreszenzübersichten erfaßt. Die tägliche Markierung der Tiere mit Fluorochromen machte die Bestimmung der Knocheneinheilungsrate möglich. Detailhistologien zeigten die Qualität der knöchernen Einheilung. Mittels computergesteuerter Bildanalyse wurde die Quantität des Knocheneinwuchses gemessen. In diesem Versuch wurden folgende Ergebnisse erzielt: Allogene BMG allein hatte keine stimulative Wirkung auf die knöcherne Heilung im ersatzstarken Lager. Der Defekt war auch nach 12 Wochen noch nicht knöchern durchbaut.Der flächenmäßige Anteil neugebildeten Knochens bei Keramik+BMG lag nach 12 Wochen bei 80 % gegenüber 33 % bei alleiniger Implantation von BMG.Keramik mit BMG zeigte eine signifikante Förderung der knöchernen Regeneration und Integration (p=0.0004) mit Bildung einiger separater Osteogenesezentren im Defektzentrum. Die osteokonduktiven Eigenschaften der BMG sind nicht stark genug ausgeprägt, um bei Minischweinen die Heilung ossärer Defekte im ersatzstarken Lager zu beschleunigen. Die Kombination von BMG mit einer Hydroxylapatitkeramik erscheint wegen der signifikanten Beschleunigung des Knocheneinwuchses bei stabiler Fixation als geeignet für die klinische Anwendung. In der Literatur ist gut belegt, daß es sich bei BMG um ein osteoinduktives Implantat handelt. Wird ein klinischer Einsatz von BMG beabsichtigt, ist die vorherige Sterilisation eine unabdingbare Voraussetzung. Die Osteoinduktivität wird durch eine Reihe von Sterilisationsverfahren drastisch reduziert. Für den Verlust der Osteoinduktivität der hier verwendeten BMG kommt als wahrscheinlichste Ursache die Sterilisation im Peressigsäure- Unterdruck- Verfahren in Frage. Der wissenschaftliche Beweis dafür steht noch aus. Die Temperatur während der Präparation hat keinen signifikanten Einfluß auf die osteoinduktive Kapazität der BMG. / Osteoinductive bone replacement substances, particularly the Bone Morphogenetic Proteins (BMP), have long been the subject of scientific interest. However, even though the temperature stability of BMP up to 60 degrees Celsius it is well documented, the procedures for the preparation of demineralized bone matrix, Bone Morphogenetic Gelatin (BMG), and the extraction of BMP called for temperatures of 2 - 4 degrees Celsius. This results in considerable costs. It was previously shown that BMP rapidly loses its osteoinductivity when left in a postmortem milieu at room temperatures. To test the hypothesis that the conditions during the preparation of BMG at room temperature do not lead to a degradation of osteoinductivity, BMG was prepared at 4 centigrade and at room temperature. BMG was then implanted in calvaria defects of 6 mm diameter in Wistar rats. Defects were evaluated at 1, 2, 4, 6, and 12 weeks. Alkaline phosphatase activity, calcium, and hydroxyproline were employed as biochemical markers of osteoneogenesis. Descriptive histology showed no differences between the two implant materials. A control group gave proof that the defects did not heal without BMG. In a second experiment, the repair of bony defects in miniature pigs after implantation of BMG was compared to a combination of BMG with a hydroxyapatite ceramic. The defects measured 9.4 mm in diameter and were located in the patellar joint surface of both distal femurs. Each animal had one defect filled with BMG and one defect filled with a pressfit implanted cylindrical hydroxyapatite ceramic and BMG. Polychromic sequential dye marking allowed the quantification of bone healing at their respective time intervals. The defect repair was evaluated at 6 and 12 weeks using X-ray-documentation, fluorescence microscopy and computer assisted histomorphometry. Defects filled with a combination of BMG with pressfit implanted hydroxyapatite cylinder showed a significantly higher degree of healing as measured in terms of radius and area of bony ingrowth. CONCLUSIONS: BMG does not lose its osteoinductive capacity when prepared at room temperature. This translates into a considerable reduction in costs.The combination of the osteoinductive properties of BMG with osteoconductive biocompatible ceramics is superior over the defect repair produced by the sole implantation of BMG only.

L'objectif principal de cette thèse est d'apporter une contribution à la modélisation de la cinétique de libération de principes actifs à partir de systèmes polymère-médicament, en tentant de réduire le "burst effect" et augmenter le temps de libération. L'idée de base est, dans un premier temps, l'encapsulation du médicament dans des liposomes, vésicules lipidiques capables de transporter le médicament, puis son inclusion dans des hydrogels polymères de manière à créer deux barrières dans le processus de libération du médicament. Les hydrogels sont à base de chitosane/gélatine et chitosane/poly(alcool vinylique) réticulés, partiellement avec de l'aldéhyde glutarique et de manière prédominante par voie ionique avec des anions sulfate ou polyphosphate. Une seconde catégorie est à base de chitosane, seul ou en combinaison avec le poly(alcool vinylique), réticulé avec de l'acide tannique à travers de nombreuses interactions hydrogène. Les hydrogels sont caractérisés d'une part par leur structure, leur morphologie, leur comportement en milieu aqueux et leur stabilité thermique; d'autre part leurs propriétés comme biomatériau (hémocompatibilité et cytotoxicité), leur capacité à inclure et libérer un composé modèle (la calcéine) libre ou encapsulé dans des liposomes. La dépendance de ces propriétés (gonflement, libération des composés solubles inclus) avec les paramètres du processus de préparation (quantité de réticulant, rapport ente les polymères utliisés, masse molaire du chitosane) est établie. Les études de cinétique de libération de la calcéine (incluse direment dans les hydrogels ou encapsulée dans les liposomes dispersés ensuite dans les hydrogels) prouve la pertinence de l'hypothèse de départ: quel que soit le type de réticulation employée pour la préparation des hydrogels, la libération de la calcéine à partir des systèmes complexes (hydrogel-liposomes-calcéine) est fortement retardée sans manifester de "burst effect". Le manuscrit conclut avec un chapitre de modélisation de la cinétique de libération à partir des systèmes employés. Etant données les applications potentielles de tels hydrogels sous forme de films pour traiter les affections de la peau, les résultats préliminaires de libération de lévofloxacine à partir d'un système transdermique qui simule les dermes humains sont montrés. / The main objective of the PhD thesis entitled “Complex polymeric biomaterials for modeling the drug release kinetics” was to bring contributions in modeling the release kinetics of active ingredients from polymer-drug systems, attempting to reduce the "burst effect"' and increase the release time. The basic idea of the thesis was, in a first stage, the encapsulation of the drug in liposomes -lipid vesicles capable of drug transport- and their subsequent inclusion in polymeric hydrogels in the rationale of creating two "barriers" in drug release process. First, obtained hydrogels are based on chitosan/gelatin and chitosan/poly(vinyl alcohol) partly covalently crosslinked with glutaraldehyde and dominantly ionically with anion sulfate or tripolyphosphate. A second category is based on chitosan hydrogels, alone or in combination with poly(vinyl alcohol), crosslinked with tannic acid through numerous hydrogen bonds. Hydrogels were characterized structurally, morphologically, in terms of the behavior in aqueous media and thermal stability, the qualities of biomaterial (hemocompatibility and cytotoxicity), the ability to include and release a model compound (calcein) free or encapsulated in liposomes. Dependence of properties (swelling, release of soluble compounds included) on the preparation process parameters (amount of crosslinker, polymers ratio used, chitosan molecular weight) is established. Performing calcein release kinetic studies (calcein included directly in hydrogels or encapsulated in liposomes subsequently dispersed in hydrogels) proves the correctness of the starting hypothesis: whatever type of crosslinking applied for the preparation of hydrogels, the release of calcein from complex systems (hydrogel-liposomes-calcein) is much delayed without manifesting practically "burst effect". The paper concludes with a chapter with modeling the release kinetics from the studied systems and with the Conclusions and Perspectives. Given the potential application of such hydrogels in the form of films for treating skin conditions, preliminary results of levofloxacin release from a transdermal system that simulates human dermis are shown.

Esta tese apresenta os resultados do estudo de eletrólitos poliméricos protônicos obtidos a base de gelatina e quitosana, modificadas através da adição de glicerol e formaldeído - ácidos acético ou clorídrico foram adicionados para promover a condutividade iônica dos filmes. Foram também preparadas blendas a partir de gelatina com quitosana, assim como filmes a base de gelatina e nanopartículas. Com exceção dos filmes com nanopartículas, todos eles possuem boa transparência, estabilidade térmica, maleabilidade, aderência ao vidro e apresentam uma superfície homogênea, sem trincas ou rachaduras. As temperaturas de transição vítrea (Tg) dos eletrólitos foram obtidas do estreitamento de linha de RMN. A taxa de relaxação spin-rede do \'ANTPOT. 1 H\' em função da temperatura mostrou um máximo bem definido cuja posição depende da concentração de ácido no caso da gelatina e da quantidade de glicerol no caso da quitosana, refletindo a alta mobilidade do próton nestes eletrólitos. As técnicas de RPE, onda contínua e pulsada, foram utilizadas para o estudo de eletrólitos dopados com \'CU\'CL\'O IND.4\'. Os valores de condutividade iônica dos eletrólitos são da ordem de \'10 POT.-5\' S/cm para os filmes de gelatina (com ácido acético ou clorídrico), quitosana e blendas e entre \'10 POT.-6\' a \'10 POT.-8\' para os eletrólitos de gelatina com nanopartículas. Estes estudos revelaram que a concentração de ácido acético ou clorídrico (na gelatina), influencia a condutividade iônica dos eletrólitos, mas, para o caso das blendas esta influência é pequena. No caso dos filmes de gelatina com nanopartículas, a condutividade diminui de forma significativa. Em relação aos eletrólitos de quitosana a condutividade iônica é influenciada pela quantidade de glicerol adicionado. Verificou-se que o aumento da temperatura até 80°C promove o aumento da condutividade iônica para todos os filmes estudados. / This thesis shows the results from the study of protonic polymer electrolytes obtained from gelatin and chitosan, modified by the addition of glycerol and formaldehyde - acetic and hydrochloric acids are added to promote the ionic conductivity of the films. Blends based on chitosan and gelatin were also prepared, as well as films based on gelatin and nanoparticles. With the exception of the films with nanoparticles, all samples presented good transparency, thermal stability, flexibility, adhesion to glass and homogeneous surface without cracks. The glass transition temperature (Tg) of the electrolytes were obtained from the NMR line narrowing. The spin-lattice relaxation rate of the \'ANTPOT. 1 H\' spin-network as a function of temperature showed a well-defined maximum whose position depends on the concentration of acid in the case of gelatin and on the glycerol content in the case of chitosan, reflecting the high mobility of the protons in the electrolytes. Continuous wave and pulsed EPR techniques were used to study the electrolytes doped with \'CU\'CL\'O IND.4\'. The values of the ionic conductivity of the electrolytes are of the order of \'10 POT.-5\' S/cm for the films of gelatin (with acetic or hydrochloric acids), chitosan and blends and from \'10 POT.-6\' to \'10 POT.-8\' for the electrolytes of gelatin with nanoparticles. These studies revealed that the concentration of acetic or hydrochloric acids (in gelatin), influences the ionic conductivity of the electrolytes but, in the case of blends, this influence is small. In the case of the films based on gelatin with nanoparticles, the ionic conductivity decreases significantly. In relation to the electrolyte based on chitosan, the ionic conductivity is influenced by the amount of glycerol added. It was found that increasing the temperature to 80°C promotes the increase of ionic conductivity for all films studied.

A pectina é uma substância polissacarídica originada de plantas, que pode ser utilizada como agente gelificante, estabilizante de compotas, em bebidas láticas e iogurtes. A gelatina, proteína, nesse caso de origem bovina, é principalmente utilizada como agente gelificante, pois, forma hidrogéis por resfriamento. O processo de irradiação por radiação gama pode causar uma variedade de modificações nas macromoléculas algumas de aplicação industrial, como é o caso de reticulação. A resposta dinâmica de materiais viscoelásticos pode ser usada para dar informação sobre o aspecto estrutural de um sistema a nível molecular. No presente trabalho, pectina com diferentes graus de metoxilação, gelatina e a mistura de ambas foram empregados para estudar a sensibilidade à radiação por meio de medidas de viscosidade. Amostras de soluções de pectina de alto teor de metoxilação (ATM) 1%, pectina de baixo teor (BTM) 1%, gelatina 0,5%,1% e 2%, e a mistura de ambas a 1% e 2% foram irradiadas com raios gama em doses de até 15kGy e taxa de dose em torno de 2kGy/h. Após irradiação, a viscosidade foi medida dentro de um período de 48 h. A viscosidade da pectina ATM e BTM diminuiu drasticamente com o aumento da dose de radiação. A gelatina, entretanto, apresentou grande resistência à radiação. Na mistura de ambas, houve predomínio do comportamento esperado para a pectina. / Pectin is a polysaccharide substance of plant origin that may be used as gelling agent, stabilizer in jams, in yogurt drinks and lactic acid beverages. Gelatin, a protein from bovine origin, in this case, is mainly used as gelling agent due to hydrogel formation during cooling. The 60 Co-irradiation process may cause various modifications in macromolecules, some with industrial application, as reticulation. The dynamic response of viscoelastic materials can be used in order to give information about the structural aspect of a system at molecular level. In the present work samples of pectin with different degree of methoxylation, gelatin and the mixture of both were employed to study the radiation sensitivity by means of viscosity measurements. Solutions prepared with citric pectin with high methoxylation content (ATM) 1 por cent, pectin with low content (BTM) 1 por cent, gelatin 0.5 por cent, 1 por cent and 2 por cent, and the mixture 1 por cent and 2 por cent were irradiated with gamma rays at different doses, up to 15 kGy with dose rate about 2 kGy/h. After irradiation the viscosity was measured within a period of 48 h. The viscosity of ATM and BTM pectin solutions decreased sharply with the radiation dose. However, the gelatin sample presented a great radiation resistance. When pectin and gelatin solutions were mixed a predominance of pectin behavior was found.

A pectina é uma substância polissacarídica originada de plantas, que pode ser utilizada como agente gelificante, estabilizante de compotas, em bebidas láticas e iogurtes. A gelatina, proteína, nesse caso de origem bovina, é principalmente utilizada como agente gelificante, pois, forma hidrogéis por resfriamento. O processo de irradiação por radiação gama pode causar uma variedade de modificações nas macromoléculas algumas de aplicação industrial, como é o caso de reticulação. A resposta dinâmica de materiais viscoelásticos pode ser usada para dar informação sobre o aspecto estrutural de um sistema a nível molecular. No presente trabalho, pectina com diferentes graus de metoxilação, gelatina e a mistura de ambas foram empregados para estudar a sensibilidade à radiação por meio de medidas de viscosidade. Amostras de soluções de pectina de alto teor de metoxilação (ATM) 1%, pectina de baixo teor (BTM) 1%, gelatina 0,5%,1% e 2%, e a mistura de ambas a 1% e 2% foram irradiadas com raios gama em doses de até 15kGy e taxa de dose em torno de 2kGy/h. Após irradiação, a viscosidade foi medida dentro de um período de 48 h. A viscosidade da pectina ATM e BTM diminuiu drasticamente com o aumento da dose de radiação. A gelatina, entretanto, apresentou grande resistência à radiação. Na mistura de ambas, houve predomínio do comportamento esperado para a pectina. / Pectin is a polysaccharide substance of plant origin that may be used as gelling agent, stabilizer in jams, in yogurt drinks and lactic acid beverages. Gelatin, a protein from bovine origin, in this case, is mainly used as gelling agent due to hydrogel formation during cooling. The 60 Co-irradiation process may cause various modifications in macromolecules, some with industrial application, as reticulation. The dynamic response of viscoelastic materials can be used in order to give information about the structural aspect of a system at molecular level. In the present work samples of pectin with different degree of methoxylation, gelatin and the mixture of both were employed to study the radiation sensitivity by means of viscosity measurements. Solutions prepared with citric pectin with high methoxylation content (ATM) 1 por cent, pectin with low content (BTM) 1 por cent, gelatin 0.5 por cent, 1 por cent and 2 por cent, and the mixture 1 por cent and 2 por cent were irradiated with gamma rays at different doses, up to 15 kGy with dose rate about 2 kGy/h. After irradiation the viscosity was measured within a period of 48 h. The viscosity of ATM and BTM pectin solutions decreased sharply with the radiation dose. However, the gelatin sample presented a great radiation resistance. When pectin and gelatin solutions were mixed a predominance of pectin behavior was found.

This work describes the realization of physically crosslinked networks based on gelatin by the introduction of functional groups enabling specific supramolecular interactions. Molecular models were developed in order to predict the material properties and permit to establish a knowledge-based approach to material design. The effect of additional supramolecular interactions with hydroxyapaptite was then studied in composite materials. The calculated properties are compared to experimental results to validate the models. The models are then further used for the study of physically crosslinked networks. Gelatin was functionalized with desaminotyrosine (DAT) and desaminotyrosyl-tyrosine (DATT) side groups, derived from the natural amino acid tyrosine. These group can potentially undergo to π-π and hydrogen bonding interactions also under physiological conditions. Molecular dynamics (MD) simulations were performed on models with 0.8 wt.-% or 25 wt.-% water content, using the second generation forcefield CFF91. The validation of the models was obtained by the comparison with specific experimental data such as, density, peptide conformational angles and X-ray scattering spectra. The models were then used to predict the supramolecular organization of the polymer chain, analyze the formation of physical netpoints and calculate the mechanical properties. An important finding of simulation was that with the increase of aromatic groups also the number of observed physical netpoints increased. The number of relatively stable physical netpoints, on average zero 0 for natural gelatin, increased to 1 and 6 for DAT and DATT functionalized gelatins respectively. A comparison with the Flory-Rehner model suggested reduced equilibrium swelling by factor 6 of the DATT-functionalized materials in water. The functionalized gelatins could be synthesized by chemoselective coupling of the free carboxylic acid groups of DAT and DATT to the free amino groups of gelatin. At 25 wt.-% water content, the simulated and experimentally determined elastic mechanical properties (e.g. Young Modulus) were both in the order of GPa and were not influenced by the degree of aromatic modification. The experimental equilibrium degree of swelling in water decreased with increasing the number of inserted aromatic functions (from 2800 vol.-% for pure gelatin to 300 vol.-% for the DATT modified gelatin), at the same time, Young’s modulus, elongation at break, and maximum tensile strength increased. It could be show that the functionalization with DAT and DATT influences the chain organization of gelatin based materials together with a controlled drying condition. Functionalization with DAT and DATT lead to a drastic reduction of helical renaturation, that could be more finely controlled by the applied drying conditions. The properties of the materials could then be influenced by application of two independent methods. Composite materials of DAT and DATT functionalized gelatins with hydroxyapatite (HAp) show a drastic reduction of swelling degree. In tensile tests and rheological measurements, the composites equilibrated in water had increased Young’s moduli (from 200 kPa up to 2 MPa) and tensile strength (from 57 kPa up to 1.1 MPa) compared to the natural polymer matrix without affecting the elongation at break. Furthermore, an increased thermal stability from 40 °C to 85 °C of the networks could be demonstrated. The differences of the behaviour of the functionalized gelatins to pure gelatin as matrix suggested an additional stabilizing bond between the incorporated aromatic groups to the hydroxyapatite. / Diese Arbeit beschreibt die Entwicklung von durch spezifische physikalische Wechselwirkungen quervernetzten Gelatine-basierten Materialien. Dazu wurden zunächst Computermodelle entwickelt, mit denen Eigenschaften der Materialien vorhergesagt werden sollten, um so eine wissensbasierte Entwicklung zu ermöglichen, um dann die Ergebnisse mit experimentellen Daten zu vergleichen und die Materialien und Modelle als Grundlage für weitere Entwicklungen zu nutzen. Gelatine wurde mit Desaminotyrosin (DAT) und Desaminotyrosyltyrosin (DATT) funktionalisiert, die sich von der natürlichen Aminosäure Tyrosin ableiten. Diese Gruppen können potentiell π-π Wechselwirkungen und Wasserstoffbrückenbindungen auch unter physiologischen Bedingungen eingehen. Es wurden Computersimulationen der Materialien mittels Moleküldynamik durchgeführt, wobei Modelle mit 0.8 Gew.-% und 25 Gew.-% Wassergehalt betrachtet wurden. Die Validierung der Modelle erfolgte durch Vergleich der errechneten mit experimentellen Daten wie z.B. der Dichte, Bindungswinkeln sowie Röntgenstreuungsspektren. Die Modelle wurden dann zur Vorhersage der molekularen Organisation der Polymerketten, Formierung physikalischer Netzpunkte und Berechnung der mechanischen Eigenschaften eingesetzt. Die Funktionalisierung der Gelatine mit DAT bzw. DATT führten wie gewünscht zur Ausbildung physikalischer Netzpunkte durch π-π Wechselwirkungen und Wasserstoffbrücken¬bindungen. Ein Schlüsselergebnis der Simulationen war, dass mit zunehmender Zahl an aromatischen Gruppen auch eine Zunahme der physikalischen Netzpunkte beobachtet werden konnte. Die funktionalisierten Gelatinen konnten durch chemoselektive Reaktion der Aminogruppen der Gelatine mit den freien Carboxylgruppen von DAT und DATT hergestellt werden. Materialien mit 25 Gew.-% Wassergehalt hatten in der Simulation und im Experiment mechanische Eigenschaften derselben Größenordnung (z.B. E-Moduln im unteren GPa-Bereich). Der Quellungsgrad der Materialien im Experiment nahm mit zunehmender Zahl an aromatische Gruppen ab (von 2800 Vol.-% auf 300 Vol.-%), wobei der Elastizitätsmodul, die Bruchdehnung sowie die Zugfestigkeit zunahmen. Die Funktionalisierung der Gelatine ist eine chemische Methode, um die Kettenanordnung auf molekularer Ebene zu beeinflussen, während die genaue Kontrolle der Trocknungs¬bedinguungen von Gelatine-basierten Materialien eine physikalische Methode mit demselben Ziel ist. Es konnte gezeigt werden, dass die Funktionalisierung von Gelatine mit DAT oder DATT zu einer stark verminderten Helixausbildungstendenz, die jedoch durch Variation der Trocknunsgbedingungen noch fein abgestimmt werden konnte. Somit konnten die mechanischen Eigenschaften von Filmen aus funktionlisierter Gelatine mit zwei unabhängigen Methoden eingestellt werden. Komposite der mit DAT oder DATT funktionalisierten Gelatine und Hydroxyapatit (HAp) zeigten deutlich verringerter Quellung. In Zugdehnungsexperimenten und rheologischen Untersuchungen zeigten die Komposite im Gleichgewichtsquellungszustand erhöhte Elastizitätsmoduln (von 200 kPa auf bis zu 2 MPa) und Zugfestigkeit (von 57 kPa auf bis zu 1.1 MPa). Darüber hinaus konnte die Übergangstemperatur Tc deutlich gesteigert werden (von ca. 40 °C auf > 85 °C). Dieses Verhalten ließ sich auf stabilisierende Bindungen zwischen den aromatische Gruppen und dem HAp zurückführen.

第22回名古屋大学年代測定総合研究センターシンポジウム平成21(2009)年度報告

A dynamic mathematical model was developed to simulate the response of polyacrylamide gel (PAG) dosimeters to a single spherical radioactive brachytherapy seed. Simulations were conducted for a high dose-rate (HDR) seed using 192Ir and a low dose-rate (LDR) seed using 125I. The model is able to predict the amount of polymer formed, the crosslink density, and the volume fraction of aqueous phase as a function of radial distance and time. Results show that PAG dosimeters can provide accurate HDR brachytherapy dosimetry at distances larger than 4 mm from the centre of the seed but will give poor results for LDR due to monomer diffusion. Experiments were conducted to evaluate the potential for using pentacosa-10,12-diynoic acid (PCDA) as the reporter molecule in micelle gel dosimeters for optical computed tomography (CT) readout. Several gels containing PCDA that was solubilized using sodium dodecyl sulfate (SDS) responded to radiation by changing from colourless to blue. Unfortunately, all phantoms that showed colour changes were turbid, making them unsuitable for optical CT scanning. Several techniques were used to produce transparent gels containing PCDA but none of these gels responded noticeably to radiation. Only turbid gels with precipitated PCDA responded, indicating that the colour change was due to oligomerization within PCDA crystals and that PCDA molecules solubilized in micelles did not undergo oligomerization. As a result, PCDA is not suitable for use in radiochromic micelle gel dosimeters. A new recipe for a radiochromic leuco crystal violet (LCV) micelle gel dosimeters with enhanced dose sensitivity was developed for optical CT readout. The recipe contains LCV, trichloro acetic acid (TCAA), Cetyl Trimethyl Ammonium Bromide (CTAB), 2,2,2-Trichloroethanol (TCE), and gelatin. Experiments were conducted to improve understanding about interactions between the different components of LCV micelle gel, highlighting the importance of pH on dose sensitivity and transparency. Results also showed the effectiveness of chlorinated compounds in improving dose sensitivity. Statistical techniques were used to build empirical models that were used to optimize the gel recipe. Additional testing in larger phantoms will be required to assess the effectiveness of the proposed gel for clinical dosimetry. / Thesis (Ph.D, Chemical Engineering) -- Queen's University, 2014-03-27 11:11:47.655

Made available in DSpace on 2014-12-17T14:06:56Z (GMT). No. of bitstreams: 1 AseneteFC_DISSERT.pdf: 1219908 bytes, checksum: bebef255f66d82cd8504a8398fd23379 (MD5) Previous issue date: 2010-12-10 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior / Inorganic pigment comprises a host lattice, which is part of the chromophore component (usually a transition metal cation) and possible components modifiers, which stabilize, add or restate the properties pigments. Among the materials with spinel, ferrites, and the chromite stand out, because they have broad technological importance in the area of materials, applicability, pigments, catalytic hydrogenation, thin film, ceramic tiles, among others. The present work, pigments containing CuFe2O4, CuCr2O4,e CuFeCrO4, were synthesized by a method that makes use of gelatin as organic precursor using their application to ceramic pigments. The pigments were characterized by X-ray diffraction (XRD), Infrared spectroscopy, scanning electron microscopy (SEM) spectroscopy in the UV-visible and Colorimetry. The results confirmed the feasibility of the synthetic route used, with respect to powders synthesized, there is the formation of spinel phase from 500?C, with an increase in crystallinity and the formation of other phases. The pigments were shown to be crystalline and the desired phases were obtained. The copper chromite have hues ranging from green to black according to the calcination temperature, while the copper chromite doped with iron had brownish. The ferrites showed copper color and darker brown to black, which may indicate an interesting factor because of the importance of black pigment / Pigmento inorg?nico ? formado por uma rede hospedeira, na qual se integra o componente crom?foro (normalmente um c?tion de metal de transi??o) e os poss?veis componentes modificadores, que estabilizam, conferem ou reafirmam as propriedades pigmentantes. Dentre os pigmentos, as estruturas tipo espin?lio se destacam por possuir ampla import?ncia tecnol?gica na ?rea de materiais, com aplica??o em pigmentos, cat?lise de hidrogena??o, filmes finos, revestimentos cer?micos, dentre outros. No presente trabalho, pigmentos contendo CuFe2O4, CuCr2O4,e CuFeCrO4 foram sintetizados por uma nova rota qu?mica usando gelatina como precursor org?nico visando sua aplica??o para pigmentos cer?micos. Os pigmentos foram caracterizados por difra??o de raios X (DRX), espectroscopia na regi?o do Infravermelho, Microscopia eletr?nica de varredura (MEV) espectroscopia na regi?o do UV-Vis?vel e Colorimetria. Os resultados confirmaram a viabilidade da rota de s?ntese utilizada; Com rela??o aos p?s-sintetizados, observase a forma??o da fase espin?lio a partir de 500oC, com um aumento da cristalinidade, bem como a forma??o de outras fases. Os pigmentos se mostraram cristalinos e as fases desejadas foram obtidas. As cromitas de cobre possuem tonalidades que v?o do verde ao preto, de acordo com a temperatura de calcina??o, enquanto que as cromitas de cobre dopadas com ferro obtiveram colora??o marrom. As ferritas de cobre apresentaram cores bem mais escuras, do marrom ao preto, o que ? uma caracter?stica interessante devido ? grande import?ncia dos pigmentos pretos na ind?stria cer?mica