Capsaicin, prostaglandin E2 (PGE2) and polydopamine (PDA) were used to target macrophage and myofibroblast activity to reduce biomaterial-induced fibrosis. The lifetime and efficacy of implantable biomedical devices are determined by the foreign body response. Immediately after implantation, proteins nonspecifically adsorb onto the material and initiate inflammation. Macrophages recruited to the site can differentiate into M1 and M2 phenotypes and upregulate inflammation and fibrosis which interferes with the intended function. M1 macrophages secrete pro-inflammatory mediators that induce chronic inflammation and promote myofibroblast differentiation while M2 macrophages are wound healing cells that suppress inflammation and regulate fibroblast activity. The fibrotic tissue is developed by myofibroblasts which produce collagen in an unregulated fashion. Collagen thickening and biomaterial encapsulation decreases efficacy and sensitive of biomedical devices. We investigated the in vitro and in vivo effects of capsaicin, PGE2 and polydopamine surface modification on macrophages and myofibroblasts. Capsaicin and PGE2 reduced poly(lactic-co-glycolic) acid (PLGA)-induced fibrosis by promoting M2 macrophage phenotype to secrete anti-inflammatory IL-10 and suppressing myofibroblast marker α-smooth muscle actin (α-SMA). Capsaicin decreased collagen by 40% and upregulated IL-10 secretion by 35% while PGE2 reduced collagen by 55% after 14 days of implantation and 40% less collagen after 42 days. PDA was used to bind an anti-fibrotic compound to the surface of a poly(dimethyl siloxane) (PDMS-PDA) to reduce fibrosis. However, PDMS-PDA controls gave an unexpected result by reducing fibrosis to the same extent as anti-fibrotic compound bound PDMS- v PDA. PDA modification reduced cellularity by 50% and significantly decreased collagen thickness by 30%. Overall, our results showed that biomaterial-induced fibrosis can be reduced by promoting M2 macrophage activity and inhibiting myofibroblast differentiation. This research demonstrates three compounds that have potential to reduce fibrosis and extend the lifetime and efficacy of implantable biomedical devices. / Thesis / Master of Applied Science (MASc) / Capsaicin, prostaglandin E2 (PGE2) and polydopamine were used to reduce scar tissue development around implanted polymers. Biomedical devices implanted in the body can undergo severe scar tissue formation, or fibrosis, and fail. Fibrosis is described by the accumulation of collagen and encapsulation of an implanted polymer. Macrophages regulate fibrosis by secreting pro-fibrotic compounds and myofibroblasts produce unregulated amounts of collagen. In this thesis, capsaicin, PGE2 and polydopamine were incorporated into implants to target macrophage and myofibroblast activity and reduce fibrosis in mice. Capsaicin and PGE2, released from a degradable polymer, altered macrophages to secrete anti-fibrotic compounds and decreased collagen by 40% and 55%, respectively. Polydopamine surface modified implants gave an unexpected result and suppressed overall cell activity to reduce fibrosis by 30%. The research conducted shows the potential of these compounds to reduce fibrosis and extend the lifetime of implantable devices.

A Organização Mundial da Saúde (OMS) relata o câncer como uma das principais causas de morte no mundo. O câncer de próstata é o segundo tipo de câncer mais prevalente em homens. Uma modalidade de tratamento que vem sendo bastante utilizada é a braquiterapia, que consiste na introdução de sementes com material radioativo no interior do orgão. Sementes de Iodo-125 podem ser inseridas soltas ou em cordas poliméricas bioabsorvíveis. As sementes em cordas poliméricas apresentam algumas vantagens, pois reduzem a taxa de migração das sementes, evento que poderia afetar a dosimetria da região e causar danos desnecessários a tecidos ou órgãos sadios. Para as sementes de Iodo-125 em cordas poliméricas, utiliza-se a poliglactina 910, (poli(ácido lático-co-ácido glicólico)) (PLGA), com cobertura de poliglactina 370 (Vicryl®). Foi proposto neste trabalho, o estudo e desenvolvimento da metodologia de síntese do biopolímero PLGA, via polimerização por abertura de anéis, assim como sua caracterização, com o propósito de utilizar o material sintetizado para fabricar um material similar ao RAPID-Strand®. Os resultados obtidos demonstram que, através da metodologia utilizada, foi possível determinar os melhores parâmetros de reação (tempo e temperatura) para o PLGA na proporção 80/20 (lactídeo/glicolídeo). Com uma temperatura de 110ºC e tempo de reação de 24h, foi possível obter 86% de rendimento, e com o aumento o tempo de reação para 72h, o rendimento é superior a 90%. Os valores de massas moleculares obtidas entre os testes, ainda são muito baixos quando comparados com os valores obtidos por outros autores na literatura (cerca de 20%). Falhas na selagem das ampolas, deixando-os vulneráveis à umidade e oxigênio, ou a falta de uma sistema eficiente de agitação podem ser possíveis explicações para estes resultados. Um reator químico adequado poderia solucionar o problema. Em relação à caracterização, as técnicas utilizadas confirmaram a estrutura esperada do polímero, e a maior proporção das unidades provenientes do dímero lactídeo, em relação ao glicolídeo. / According to World Health Organization (WHO), cancer is a leading cause of death worldwide. Prostate cancer is the second most common cancer in men. A method of radiotherapy which has been extensively used is brachytherapy, where radioactive seeds are placed inside the area requiring treatment. Iodine-125 seeds can be placed loose or stranded in bioabsorbable polymers. Stranded seeds show some advantages, since they reduce the rate of seed migration, an event that could affect the dosimetry of the prostate and cause unnecessary damage to healthy tissues or organs. For Iodine-125 stranded seeds, polyglactin 910 (poly(lactic-co-glycolic acid)) (PLGA), with a coverage of polyglactin 370 (Vicryl ®) is used. It was purposed in this dissertation, the study and development of the synthesis methodology for PLGA via ring-opening polymerization, as well as its characterization, with the objective of using the synthesized material to manufacture a material similar to RAPID Strand®. The results obtained show that it was possible to determine the optimal reaction parameters (time and temperature) for PLGA in 80/20 (lactide/glycolide) ratio. Using a temperature of 110 ° C and reaction time of 24h, a yield of 86% was obtained, and increasing the reaction time to 72 hours, the yield was higher than 90%. The molecular mass values obtained from the samples are still very low compared to those obtained by other authors in the literature (about 20%). Failures in the sealing of vials, leaving them vulnerable to moisture and oxygen, or lack of an efficient stirring system might be possible explanations for these results. A suitable chemical reactor could solve the problem. Regarding polymer characterization, all techniques used not only confirmed the expected structure of the polymer, but also showed the highest proportion of lactide units compared to to glycolide units.

A Organização Mundial da Saúde (OMS) relata o câncer como uma das principais causas de morte no mundo. O câncer de próstata é o segundo tipo de câncer mais prevalente em homens. Uma modalidade de tratamento que vem sendo bastante utilizada é a braquiterapia, que consiste na introdução de sementes com material radioativo no interior do orgão. Sementes de Iodo-125 podem ser inseridas soltas ou em cordas poliméricas bioabsorvíveis. As sementes em cordas poliméricas apresentam algumas vantagens, pois reduzem a taxa de migração das sementes, evento que poderia afetar a dosimetria da região e causar danos desnecessários a tecidos ou órgãos sadios. Para as sementes de Iodo-125 em cordas poliméricas, utiliza-se a poliglactina 910, (poli(ácido lático-co-ácido glicólico)) (PLGA), com cobertura de poliglactina 370 (Vicryl®). Foi proposto neste trabalho, o estudo e desenvolvimento da metodologia de síntese do biopolímero PLGA, via polimerização por abertura de anéis, assim como sua caracterização, com o propósito de utilizar o material sintetizado para fabricar um material similar ao RAPID-Strand®. Os resultados obtidos demonstram que, através da metodologia utilizada, foi possível determinar os melhores parâmetros de reação (tempo e temperatura) para o PLGA na proporção 80/20 (lactídeo/glicolídeo). Com uma temperatura de 110ºC e tempo de reação de 24h, foi possível obter 86% de rendimento, e com o aumento o tempo de reação para 72h, o rendimento é superior a 90%. Os valores de massas moleculares obtidas entre os testes, ainda são muito baixos quando comparados com os valores obtidos por outros autores na literatura (cerca de 20%). Falhas na selagem das ampolas, deixando-os vulneráveis à umidade e oxigênio, ou a falta de uma sistema eficiente de agitação podem ser possíveis explicações para estes resultados. Um reator químico adequado poderia solucionar o problema. Em relação à caracterização, as técnicas utilizadas confirmaram a estrutura esperada do polímero, e a maior proporção das unidades provenientes do dímero lactídeo, em relação ao glicolídeo. / According to World Health Organization (WHO), cancer is a leading cause of death worldwide. Prostate cancer is the second most common cancer in men. A method of radiotherapy which has been extensively used is brachytherapy, where radioactive seeds are placed inside the area requiring treatment. Iodine-125 seeds can be placed loose or stranded in bioabsorbable polymers. Stranded seeds show some advantages, since they reduce the rate of seed migration, an event that could affect the dosimetry of the prostate and cause unnecessary damage to healthy tissues or organs. For Iodine-125 stranded seeds, polyglactin 910 (poly(lactic-co-glycolic acid)) (PLGA), with a coverage of polyglactin 370 (Vicryl ®) is used. It was purposed in this dissertation, the study and development of the synthesis methodology for PLGA via ring-opening polymerization, as well as its characterization, with the objective of using the synthesized material to manufacture a material similar to RAPID Strand®. The results obtained show that it was possible to determine the optimal reaction parameters (time and temperature) for PLGA in 80/20 (lactide/glycolide) ratio. Using a temperature of 110 ° C and reaction time of 24h, a yield of 86% was obtained, and increasing the reaction time to 72 hours, the yield was higher than 90%. The molecular mass values obtained from the samples are still very low compared to those obtained by other authors in the literature (about 20%). Failures in the sealing of vials, leaving them vulnerable to moisture and oxygen, or lack of an efficient stirring system might be possible explanations for these results. A suitable chemical reactor could solve the problem. Regarding polymer characterization, all techniques used not only confirmed the expected structure of the polymer, but also showed the highest proportion of lactide units compared to to glycolide units.

Regulation of gene expression using small interfering RNA (siRNA) is a promising strategy for research and treatment of numerous diseases. However, siRNA cannot easily cross the cell membrane due to its inherent instability, large molecular weight and anionic nature. For this reason, a carrier that protects, delivers and unloads siRNA is required for successful gene silencing. The goal of this research was to develop a potential siRNA delivery system for in vitro and in vivo applications using cationic polymers, chitosan and polyethylenimine (PEI), poly(ethylene glycol) (PEG), mannose, and poly(D,L-lactic-co-glycolic acid) (PLGA). Furthermore, the delivery system was constructed in two different ways to explore the effect of mannose location in the structure. In the first approach, mannose and PEG were directly conjugated to the chitosan/PEI backbone, while mannose was connected to the chitosan/PEI backbone through PEG spacer in the second approach. First, the ability of modified chitosan polymers to complex and deliver siRNA for gene silencing was investigated. Despite the modified chitosan polymers successfully formed nanoplexes with siRNA, entered target cells and reduced cytotoxicity of unmodified chitosan, they showed limited gene silencing efficiency. For this reason, modified PEIs were examined to improve in vitro gene knockdown. The modified PEI polymers also complexed with siRNA and facilitated endocytosis of the nanoplexes. In addition, the modifications reduced inherent cytotoxicity of unmodified PEI without compromising the gene silencing efficiency on both mRNA and protein levels. Interestingly, we found that complexation of siRNA with PEI-PEG-mannose resulted in higher cell uptake and gene silencing than complexes made with mannose-PEI-PEG. Finally, the effect of sustained release of the mannosylated pegylated PEI/siRNA nanoplexes on gene silencing was tested by encapsulating the nanoplexes within PLGA microparticles. The modified PEIs enhanced the entrapment efficiency of siRNA into the particles and resulted in reduced initial burst followed by sustained release. Incorporating the modified PEIs increased cellular uptake of siRNA, whereas it did not enhance in vitro gene knockdown efficiency due to the sustained release properties. The modified PEIs reduced the in vitro cytotoxicity and in vivo hepatotoxicity of the PLGA microparticles. In addition, encapsulating the nanoplexes into PLGA microparticles further reduced the cytotoxicity of PEI. Throughout the study, the second structure was proven more efficacious than the first structure in cellular uptake, gene silencing, siRNA encapsulation, and sustained release. We have developed novel polymeric siRNA delivery systems that enhance delivery efficiency and cellular uptake of siRNA. They have great potential for utility as a long-acting siRNA delivery system in biomedical research.

L'administration de protéines de façon locale et prolongée à partir de microsphères biodégradables de PLGA présente un réel intérêt thérapeutique (diminution du nombre d'injections, potentialisation de l'activité, diminution des effets secondaires), plus particulièrement, dans le domaine de l'ingénierie tissulaire pour l'apport de facteurs de croissance. Cependant, la faible stabilité des protéines dans ces systèmes limite leur développement. Dans ce travail, des stratégies ont été mises en place pour préserver l'intégrité de protéines à la fois lors des étapes d'encapsulation et de libération. Dans une étude préliminaire, des protéines modèles et thérapeutiques ont été précipitées afin d'éviter leur dénaturation pendant leur future encapsulation. Des particules submicroniques ont ainsi été formées par ajout d'un non solvant et d'un sel à une solution aqueuse de protéine. Après optimisation des rendements de précipitation, ces particules de protéines ont été microencapsulées par un procédé de simple émulsion (s/o/w). Aucune perte d'activité n'a été observée et ce, sans stabilisant. Ensuite, pour pallier au ralentissement de la libération après le premier jour d'incubation des microsphères, l'interaction protéine-polymère a été modélisée et des composés capables de limiter l'adsorption du lysozyme sur le PLGA ont été sélectionnés, notamment le poloxamer 188. La précipitation du lysozyme avec du poloxamer 188 avant encapsulation a ainsi conduit à une libération continue de protéine active pendant trois semaines sans effet burst à partir de microsphères de PLGA et pendant plus de six semaines avec un copolymère tribloc de PLGA-PEG-PLGA.

This research centers on the fabrication, characterization, and engineering of inverse opal scaffolds, a novel class of three-dimensional (3D) porous scaffolds made of biocompatible and biodegradable polymers, for applications in tissue engineering and regenerative medicine. The unique features of an inverse opal scaffold include a highly ordered array of pores, uniform and finely tunable pore sizes, high interconnectivity, and great reproducibility. The first part of this work focuses on the fabrication and functionalization of inverse opal scaffolds based on poly(D,L-lactic-co-glycolic acid) (PLGA), a biodegradable material approved by the U.S. Food and Drug Administration (FDA). The advantages of the PLGA inverse opal scaffolds are also demonstrated by comparing with their counterparts with spherical but non-uniform pores and poor interconnectivity. The second part of this work shows two examples where the PLGA inverse opal scaffolds were successfully used as a well-defined system to investigate the effect of pore size of a 3D porous scaffold on the behavior of cell and tissue growth. Specifically, I have demonstrated that i) the differentiation of progenitor cells in vitro was dependent on the pore size of PLGA-based scaffolds and the behavior of the cells was determined by the size of individual pores where the cells resided in, and ii) the neovascularization process in vivo could be directly manipulated by controlling a combination of pore and window sizes when they were applied to a mouse model. The last part of this work deals with the novel application of photoacoustic microscopy (PAM), a volumetric imaging modality recently developed, to tissue engineering and regenerative medicine, in the context of non-invasive imaging and quantification of cells and tissues grown in PLGA inverse opal scaffolds, both in vitro and in vivo. Furthermore, the capability of PAM to monitor and quantitatively analyze the degradation of the scaffolds themselves was also demonstrated.

Implantable sensors have been extensively investigated to facilitate diagnosis or to provide a means to generated closed loop control of therapy by yielding in vivo measurements of physical and chemical signals. Biodegradable sensors which degrade gradually after they are no longer functionally needed exhibit great potential in acute or shorter-term medical diagnostic and sensing applications due to the advantages of (a) exclusion of the need to a secondary surgery for sensor removal, and (b) reduction of the risk of long-term infection. The objective of this research is to design and characterize microfabricated RF wireless pressure sensors that are made of completely biodegradable materials and degrade at time-controlled manner (in the order of years and months). This was achieved by means of investigation of appropriate biodegradable materials and development of appropriate fabrication processes for these non-standard (Microelectromechanical systems) MEMS materials. Four subareas of research are performed: (1) Design of sensors that operate wirelessly and are made of biodegradable materials. The structure of the wireless sensor consists a very compact and relatively simple design of passive LC resonant circuits embedded in a polymer dielectric package. To design the sensor with a particular resonant frequency range, an electromagnetic model of the sensor and a mechanical model for circular plate are developed. The geometry of the sensor is established based on the analytical and finite element simulations results. (2) Investigation of the biodegradable materials in the application of implantable biodegradable wireless sensors to achieve controllable degradation lifetimes. Commercially available and FDA approved biodegradable polymers poly(L-lactic acid) (PLLA) and a "shell-core" structure of poly(lactic-co-glycolic acid) (PLGA) and polyvinyl alcohol (PVA) are utilized as the dielectric package for slow and rapid degradation sensors, respectively. Biodegradable metallic zinc and zinc/iron couples are chosen as conductor materials. The degradation behavior of Zn and Zn/Fe-couple are investigated in vitro. (3) Development of novel fabrication processes. The process exploit the advantages of MEMS technology in fabricating miniaturized devices, while protecting vulnerable biodegradable materials from the strong and/or hazardous chemicals that are commonly used in conventional MEMS fabrication process. These new processes enable the fabrication of biocompatible and biodegradable 3-D devices with embedded, near-hermetic cavities. (4) Testing the pressure response functionality and studying the degradation behavior of the wireless biodegradable pressure sensors. Both PLLA-based and PLGA/PVA-based sensors are characterized in vitro by being immersed in 0.9% saline for prolonged time. All the sensors exhibit three stages of behavior in vitro: equilibration, functional lifetime, and performance degradation. During the functional lifetime, most sensors exhibit fully stable functionality. The PLLA-based sensors show no significant weight loss within 8 month and are expected to fully degrade after 2 years, while the PLGA/PVA-based sensors can degrade completely within 26 days.

No description available.

Η βλέννα του σαλιγκαριού έχει χρησιμοποιηθεί στην ιατρική από την αρχαιότητα από την εποχή του Ιπποκράτη, ο οποίος είχε προτείνει τη χρήση της βλέννας για την καταπολέμηση του πόνου, εγκαυμάτων και άλλων τραυμάτων. Πρόσφατη επιστημονική μελέτες του εκκρίματος του σαλιγκαριού Helix aspersa επιβεβαίωσαν ότι η βλέννα περιέχει ένα ασυνήθιστο συνδυασμό φυσικών προϊόντων με ευεργετικές και θεραπευτικές ιδιότητες στο ανθρώπινο δέρμα. Η βλέννα του σαλιγκαριού παρουσιάζει σημαντικό οικονομικό - εμπορικό ενδιαφέρον, ως προς την αξιοποίηση των χημικών συστατικών της όπως η αλλαντοΐνη και το γλυκολικό οξύ που χρησιμοποιούνται ευρύτατα ως δραστικά συστατικά κατά την παρασκευή φαρμακευτικών και καλλυντικών προϊόντων. Η αλλαντοΐνη είναι μία ετεροκυκλική οργανική ένωση που παράγεται από την κατάλυση των πουρινών από το ένζυμο καταλάση. Παρουσιάζει μια μακρά ιστορία όσον αφορά στη χρήση της σε μια ποικιλία από τοπικά φάρμακα και καλλυντικά προϊόντα για την περιποίηση του δέρματος. Το γλυκολικό οξύ είναι το μικρότερο α-υδροξύ - οξύ (AHA). Χάρη στην εξαιρετική ικανότητά του να διαπερνάει το δέρμα, βρίσκει εφαρμογές σε διάφορα προϊόντα φροντίδας του δέρματος, για τη βελτίωση της εμφάνισης και της υφής του δέρματος μειώνοντας ρυτίδες, ουλές ακμής, υπέρχρωση και άλλα και σε άλλες δερματικές παθήσεις. Στην παρούσα εργασία έγινε προσπάθεια ανάπτυξης μεθοδολογιών για τον ποιοτικό και ποσοτικό προσδιορισμό της αλλαντοΐνης και του γλυκολικού οξέος. Με χρωματογραφία υψηλής απόδοσης (HPLC-DAD) σε στήλη Synergi RP (Phenomenex ®) επετεύχθη πολύ καλός διαχωρισμός εντός 6 min. Οι τελικές συνθήκες διαχωρισμού (ισοκρατική έκλουση με εκλούτη ρυθμιστικό διάλυμα 10 mM KH2PO4 pH 2.7 και η ροή ρυθμίστηκε στο 0.7 mL/min και στους 30 C) και προκατεργασίας δείγματος (αραίωση της βλέννας στο ρυθμιστικό διάλυμα, θέρμανση στους 60 C για 20 λεπτά και εκχύλιση με εξάνιο) επιλέχθηκαν μετά από μελέτη διαφόρων παραμέτρων που αφορούν στη σύσταση του εκχυλιστικού μέσου και της κινητής φάσης. Η μέθοδος επικυρώθηκε ως προς τα αναλυτικά της χαρακτηριστικά (γραμμικότητα, επαναληψιμότητα, ακρίβεια και σταθερότητα). Ανάλυση της βλέννας του σαλιγκαριού Helix aspersa έδειξε ότι περιέχει 48.610 ± 0.002, 47.590 ± 0.001, 52.820 ± 0.001 mg/L αλλαντοΐνης και 3753.01 ± 0.01, 3170.51 ± 0.02, 1979.23 ± 0.02 mg/L γλυκολικού οξέος για τις τρεις παρτίδες που αναλύσαμε, αντίστοιχα. Η προτεινόμενη μεθοδολογία χρησιμοποιήθηκε για την ποσοτική ανάλυση τριών καλλυντικών κρεμών (Elicina της εταιρίας Cosméticos Elicina Ltda, Santiago, Χιλή, Labcconte της εταιρίας Cosméticos Concepción Ltda, Χιλή και μια κρέμα από την εταιρία Helix ir στην Κρήτη) στις οποίες η βλέννα του σαλιγκαριού αναγράφεται να περιέχεται σε υψηλό ποσοστό (85%). Τα αποτελέσματα μας δείχνουν ότι τα καλλυντικά σκευάσματα περιέχουν 0.110 ± 0.003, 0.260 ± 0.010 , 0.370 ± 0.001 mg/L αλλαντοΐνης και 4.520 ± 0.010, 5.350 ± 0.010, 5.690 ± 0.001 mg/L γλυκολικού οξέος, αντίστοιχα. / The snail mucus has been used in medicine since the time of Hippocrates, who proposed the use of mucus to combat pain, burns and other wounds. Recent scientific studies of the snail secretion Helix Aspersa confirmed that the snail contains an unusual combination of natural products which are beneficial for human skin. The last time the mucus of the snail has important economic - commercial interest in the use of chemical components such as allantoin and glycolic acid are widely used as active ingredients in the manufacture of pharmaceutical and cosmetic products. Allantoin is a heterocyclic organic compound produced by the breakdown of purines by the enzyme catalase. It has a long history in the use of a variety of topical medications and cosmetics for skin care. The glycolic acid is the smallest alpha-hydroxy acid (AHA). Thanks to its excellent ability to penetrate the skin, it finds applications in various skin care products, for improving the appearance and texture of skin by reducing wrinkles, acne scars, hyperpigmentation and also can improve many other skin disorders. In this study we developed analytical methodology for qualitative and quantitative determination of allantoin and glycolic acid. Application of highperformance chromatography (HPLC-DAD) on a Synergi RP (Phenomenex ®) column has provided a very good separation within 6 min. The final separation (isocratic elution with buffer 10 mM KH2PO4 pH 2.7 as eluent and flow rate 0.7 mL/min at 30 °C) and sample pretreatment (by dilution the mucus in the buffer, heated at 60 °C for 20 min and extracted with hexane) were selected after a study of various parameters relating to the extraction medium and the mobile phase. The method was validated in terms of analytical characteristics (linearity, repeatability, accuracy and stability). Analysis of the snail secretions Helix aspersa showed that it contains 48.610 ± 0.002, 47.590 ± 0.001, 52.820 ± 0.001 mg/L allantoin and 3753.01 ± 0.01, 3170.51 ± 0.02, 1979.23 ± 0.02 mg/L glycolic acid for three batches that we analyzed, respectively. The methodology was used for quantitative analysis of three cosmetic creams (Elicina from the company: Cosméticos Elicina Ltda, Santiago, Chile, Labcconte from the comany: Cosméticos Concepción Ltda, Chile and a cream from the company: Helix ir in Crete) where the snail mucus is deemed to be about 85%. Our results show that cosmetic products contain 0.110 ± 0.003, 0.260 ± 0.010 , 0.370 ± 0.001 mg/L allantoin and 4.520 ± 0.010, 5.350 ± 0.010, 5.690 ± 0.001 mg/L glycolic acid, respectively.

Orientador: Eliana Aparecida de Rezende Duek / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia Mecanica / Made available in DSpace on 2018-08-14T20:10:35Z (GMT). No. of bitstreams: 1 Silva_KatiaFernanda_M.pdf: 16700696 bytes, checksum: 568261b128b361204100ac55aba7640b (MD5) Previous issue date: 2008 / Resumo: A Ciência dos Biomateriais é uma área de conhecimento multidisciplinar e está relacionada a implantes cirúrgicos e dispositivos médicos e odontológicos. Dentre as atuais aplicações dos biomateriais, a utilização de polímeros biorreabsorvíveis como arcabouço (scaffolds) para cultura de células tem se destacado como alternativa para tratamento de lesões e perda de tecidos. O objetivo deste trabalho foi obter e caracterizar arcabouços da blenda de poli(e-caprolactona) (PCL) e poli(D,L-ácido lático-co-ácido glicólico) (PLGA) nas diferentes composições (70/30, 50/50 e 30/70), preparados pelo método de fusão com adição e lixiviação de citrato de sódio. Os resultados obtidos através das análises de MEV evidenciaram que as amostras da blenda de PCL/PLGA 30/70 possuem tamanhos e quantidades de poros mais homogêneos quando comparadas às suas análogas de PCL/PLGA nas composições 50/50 e 70/30. Os materiais foram utilizados como arcabouço para cultura de osteoblastos e o estudo in vivo foi realizado pelo implante em tíbia de ratos. A cultura de células nas blendas de PCL/PLGA 70/30 e 30/70 mostraram um padrão de adesão e proliferação satisfatório, com intensa atividade celular comparado com a blenda na composição 50/50. No estudo in vivo as amostras de PCL/PLGA 30/70 com cultura apresentaram um crescimento celular mais intenso quando comparada com as blendas nas composições 70/30 com cultura, e nas diferentes composições sem cultura de células. Os resultados mostraram que a técnica utilizada no preparo das amostras é útil na confecção de arcabouços altamente porosos. Em função das análises in vitro e in vivo as blendas de PCL/PLGA 30/70 foram os arcabouços mais indicados para aplicações na engenharia de tecidos ósseos. / Abstract: The use of bioreabsorbable polymers as scaffolds for the cells culture has received special attention as an alternative for the treatment of lesions and the loss of tissue. The aim of this work was to obtain and to characterize porous scaffolds of poly(e-caprolactone) (PCL) and poly(D,Llactic acid-co-glycolic acid) (PLGA), blends, in different composition (30/70, 50/50 e 70/30), prepared by melting method with addition and leaching of sodium citrate. The morphology of samples obtained by SEM showed that PCL/PLGA 30/70 blends presented size and size distribution of porous more homogeneous when compared to PCL/PLGA 50/50 and 30/70. The culture of cells in PCL/PLGA 70/30 and 30/70 showed a satisfactory adhesion and proliferation, with intense cellular activity compared to PCL/PLGA 50/50. In the in vivo study, the samples of PCL/PLGA 30/70 showed a higher cellular grown compared to the results obtained in in vivo study of 70/30 blends with cells, 70/30 and 30/70 without cells. The results showed that the proposed technique allowed the preparation of highly porous scaffolds and the in vitro and in vivo showed that PCL/PLGA 30/70 blends were the most suitable scaffolds for applications in the bone tissue engineering. / Mestrado / Materiais e Processos de Fabricação / Mestre em Engenharia Mecânica