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Different structures of non-viral cationic polymer delivery vehicles, including charge center type, molecular weight and degradability, could significantly affect toxicity, release of nucleic acid and transfection efficiency. Poly(glycoamidoamine)s (PGAAs) contained different carbohydrate and secondary amine moieties and showed high transfection efficiency to different cell lines in a nontoxic manner. The "proton sponge hypothesis" has attempted to relate the buffering capacity to endosomal release of polyethylenimine (PEI) based polyplexes, which could contribute to high transfection efficiency. Secondary amine structures rendered PGAAs buffering capacity around physiological pH. To test the feasibility of the mechanism for PGAAs, new no buffering capacity guanidine or methylguanidine containing poly(glycoamidoguanidine)s (PGAGs) were synthesized. PGAGs formed stable polyplexes with pDNA from N/P (# secondary amine or guanidine group on polymer backbone / # phosphate group on pDNA backbone) ratio 3. PGAG based polyplexes expressed low cytotoxicity and were internalized by 90% of cells at N/P 25. Furthermore, two PGAG based polyplexes showed higher transfection efficiency from N/P 5 to 30 than their PGAA based analogs. These data suggested the low transfection could be due to the difficulties to release pDNA from polyplexes; also, the "proton sponge theory" could not explain the higher transfection efficiency by some PGAGs. Degradation of delivery vehicles could potentially release pDNA in cells and increase transfection efficiency. PGAAs degraded rapidly at physiological conditions and the proposed mechanism was amide hydrolysis. Typically, amide groups are stable and hydrolyze slowly in absence of enzyme. Different models mimicking PGAAs were synthesized to study the fast hydrolysis. Amide groups showed asymmetric hydrolysis. Different hydrolysis behaviors suggested neighboring group participation of two terminal groups to induce rapid amide hydrolysis. These new models could potentially be used to design new polymer delivery vehicles with various degradation profiles. / Master of Science

Broilers are raised indoors on high density farms with bedding/litter to trap their manure. Ammonia gas, which is produced as the manure decomposes, has adverse effects on human health, bird welfare and the environment. Using litter amendments can reduce the amount and, consequently, the effects of ammonia emitted from broiler houses. The objective of this study was to determine the effectiveness of a biodegradable litter amendment (BLA) in reducing ammonia emitted from a broiler house. A pilot scale test was set up with six adjacent, individually ventilated rooms and a stocking density of 0.07 m² per bird. The birds were fed with a standard commercial, corn and soybean meal based diet and water was provided ad libitum. The first flock was grown on 10 cm of fresh, kiln-dried pine shavings, while subsequent flocks were grown on top-dressed reused litter. The two treatments (control (CTL) and BLA) were randomly assigned to the six rooms after flock 1, to give three replicates per treatment. The exhaust air from the rooms was sampled for ammonia concentration for two days each week starting at four days of age to determine the amount of ammonia emitted. Over three subsequent flocks, the total mass of ammonia emitted from rooms treated with BLA was 31% to 47% lower than the control. Ammonia emitted per bird grown on treated litter and per kg of harvested bird weight was 32% to 44% lower, and the exhaust fans ran 7% to 22% less than CTL over the same period. For both BLA and CTL, the amount of ammonia emitted generally increased with bird age and litter reuse. The study showed that BLA effectively reduced ammonia emitted from a broiler house and that there are potential energy savings from using the amendment. However, ammonia emitted from the BLA rooms during the final flock was 57% higher than CTL, which was attributed to insufficient water (less than 18% moisture by weight) to support the reaction between BLA and ammonia. / Ph. D.

Los tendones juegan un papel clave en la mecánica articular. Estos tejidos poseen una actividad celular escasa y poca capacidad de regenerarse; debido a ello cuando sufren una lesión grave, se requiere el uso de prótesis sintéticas. Debido a los numerosos problemas que presentan las prótesis actuales, se presenta un nuevo concepto de prótesis tendinosa diseñada siguiendo las estrategias de la Ingeniería Tisular del tendón. El concepto que presentamos es el de una prótesis apta para tendón, que tras su implante, se degrada mientras induce la autoregeneración del tejido natural. Para conseguirlo, la prótesis se cultiva, previamente o durante el implante, con células capaces de inducir la regeneración del tejido natural. Para acelerar esta regeneración se puede hacer uso de factores estimulantes, tales como factores de crecimiento y biorreactores. La prótesis consta de un trenzado hueco de ácido poli-L-láctico (PLA), que reproduce el comportamiento mecánico del tendón o ligamento natural. El hueco del trenzado va relleno de una combinación de micropartículas de PLA y ácido hialurónico (HA), que sirven de soporte (scaffold) a las células precursoras de los tenocitos. Este combinado es introducido mediante una jeringuilla en el interior del trenzado. La parte exterior del trenzado lleva un recubrimiento de HA que evita las adherencias de la prótesis con los tejidos circundantes, permitiendo, sin embargo, el suministro de nutrientes a las células del interior de la trenza. Objetivos Se pretende verificar que el nuevo concepto de prótesis es apto para tal aplicación. Para ello una vez diseñado el prototipo se ha realizado una caracterización física, química y mecánica, para cerciorarnos que las propiedades de los materiales que la forman se asemejan a las propiedades del tejido a reemplazar. Además se ha realizado una caracterización biológica para observar el comportamiento de diferentes fuentes celulares, al mismo tiempo que se han usado factores estimulantes (factores de crecimiento y biorreactor) para estudiar la respuesta celular a estos estímulos y observar si se produce diferenciación celular, incremento en la producción de matriz extracelular y alineamiento celular, entre otros. Elementos de la metodología a destacar Se ha utilizado numerosas técnicas para la fabricación y caracterización de los materiales, incluyendo el diseño y la fabricación de un biorreactor. Resultados logrados. Tras el estudio de caracterización física, química y mecánica de los materiales se ha demostrado que poseen características idóneas para ser utilizados en la fabricación de una futura prótesis tendinosa. Con respecto a los ensayos biológicos se ha podido comprobar que las células cultivadas muestran un buen comportamiento proliferando y adhiriéndose al material. Además, los resultados indican que el uso de los factores estimulantes promueve la diferenciación tenocítica, demostrando que las células mesenquimales provenientes de médula ósea son una fuente celular apropiada para utilizarlas en la regeneración tendinosa. / Araque Monrós, MC. (2013). DESARROLLO DE UNA PRÓTESIS REGENERATIVA DE TENDÓN [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/30313