Polycaprolactone (PCL) is a biodegradable synthetic polymer that is currently used in a number of biomedical applications. A number of concerns have been raised over the toxicity of initiators commonly employed for the synthesis of PCL. Therefore, more biocompatible initiators have been studied. The biocompatibility of PCL, itself, is adequate; however, improved bioactivity is desirable for several applications. Copolymerisation, and incorporation of bioactive fillers can both be used as ways of enhancing the bioactivity of PCL. Therefore, the global objective of this project was to enhance the bioactivity of PCL by copolymerisation of PCL with poly(ethylene glycol) (PEG) using a biocompatible calcium-based initiator. This calcium-initiator was expected to leave potentially bioactive calcium-initiator residues in the synthesised copolymers. A study of the ring-opening polymerisation of epsilon-caprolactone (CL) in the presence of a poly(ethylene glycol) (PEG) / calcium hydride (CaH2) co-initiation system was performed. Polymerisation kinetics were monitored by following the degree of conversion of CL by Fourier transform-Raman (FT-Raman) spectroscopy and 1H nuclear magnetic resonance spectroscopy (NMR). Resultant PCL-b-PEG-b-PCL (PCL/PEG/PCL) triblock copolymers were analysed by NMR and gel permeation chromatography (GPC). The observed rates of polymerisation for the synthesis of PCL/PEG/PCL triblock copolymers using the PEG / CaH2 co-initiator were much lower than expected. 1H NMR and Raman microspectroscopy analysis showed that the concentration of the active calcium-PEG alkoxide was much lower than the initial feed concentration of PEG. Even so, the molecular weight of PCL/PEG/PCL triblock copolymers could be predicted from the CL : PEG feed ratio. This was found to be due to a fast reversible transfer process. Inductively coupled plasma-atomic emission spectroscopy (ICP-AES) analysis of solutions containing acid digested, pure PCL/PEG/PCL copolymers showed calcium concentrations at equal to or greater than 77 % of the calcium feed concentration. These calcium-initiator residues were isolated and their structures confirmed by Fourier transform infrared-attenuated total reflectance spectroscopy (FTIR-ATR). They were found to be a mixture of calcium hydroxide (Ca(OH)2) and calcium carbonate (CaCO3). The effect of calcium-initiator residues on the in vitro mineralisation of PCL/PEG/PCL triblock copolymers, as well as the same effect on a model calcium-salt-doped PCL homopolymer system, was studied by immersion in simulated body fluid (SBF). In the model studied, PCL homopolymer was doped with low concentrations (0.2 - 2 w / w % Ca) of Ca(OH)2, or CaCO3. Results from the model study showed calcium phosphate (CaP) mineral deposition on Ca(OH)2-doped PCL, and not on CaCO3-doped PCL. This was attributed to the higher solubility of Ca(OH)2, compared to CaCO3. Minimal CaP deposition was observed on PCL/PEG/PCL triblock copolymers. This was attributed to the low Ca(OH)2 concentration in these samples. For all mineralised samples in the SBF studies, the formation of carbonated HAP was observed. Overall, the synthesis of PCL/PEG/PCL copolymers using the PEG / CaH2 co-initiator was found to be a suitable method for preparing reproducible materials. The calcium-based initiator was also found to have potential for increasing the bioactivity of PCL-based materials.

Orientador: Adriana Aigotti Haberbeck Brandão / Banca: Adriana Aigotti Haberbeck Brandão / Banca:Ana Lia Anbinder / Banca: Rosilene Fernandes da Rocha / Resumo: A osteoporose, doença caracterizada pela perda de massa óssea, tem sido alvo de estudos nos últimos anos. Fraturas decorrentes da osteoporose são muito comuns e podem apresentar consolidação mais lenta. O objetivo deste trabalho foi avaliar o efeito do risedronato (medicamento alopático) e da Calcarea phosphorica 6CH (medicamento homeopático) no processo de reparo ósseo em ratos machos com osteoporose induzida por castração. Para tanto, foram utilizados oitenta e quatro ratos de três meses de idade separados em quatro grupos de vinte e um animais, sendo três grupos submetidos à castração e um grupo a falsa cirurgia (sham). Um mês após, foram realizadas lesões ósseas monocorticais na tíbia de todos os animais e a partir do dia seguinte, os respectivos tratamentos foram iniciados de acordo com os seguintes grupos: CR - castrado/ risedronato (1mg/kg/dia); CCp - castrado/Calcarea phosphorica 6CH (três gotas/dia); CP - castrato/placebo e SP - sham/placebo que receberam apenas três gotas ao dia de água destilada. Os animais foram sacrificados aos sete, catorze e vinte e oito dias após o início do tratamento e as tíbias removidas. Radiografias digitais foram realizadas e avaliadas pelo programa Image Tool para obter a densidade óptica na área do defeito. Então as tíbias foram descalcificadas e processadas para a realização das análises histológicas. A histomorfometria mediu a porcentagem de osso formado utilizando um retículo graduado colocado no centro da lesão através do programa Image J. Para a análise estatística, os dados foram submetidos aos testes de ANOVA, Tukey e Dunnett, ao nível de 5%. Segundo a análise da densidade óptica, o grupo CCp apresentou os melhores resultados aos sete e catorze dias, mas foi superado pelo grupo CR aos vinte e oito dias. Segundo a histomorfometria o grupo SP apresentou o melhor resultado aos sete dias, ... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Osteoporosis, a disease characterized by progressive bone loss, has been the target of several studies lately. It results in a much higher risk for fractures and might cause slower bone consolidation. The aim of this work was to study the effects of Risedronate (allopathic medicine) and Calcarea phosphorica 6CH (homeopathic medicine) to repair bone lesions in male rats with osteoporosis, induced by castration. For this, eighty-four three-months-old rats were used divided in four groups of twenty-one animals. Three groups where castrated and one group was submitted to Sham surgery. One month later, monocortical lesions were made in all animals' tibiae and after one day they began the different treatments according to the following groups: CR - castrated/Risedronate (1mg/kg/day); CCp - castrated/Calcarea phosphorica 6CH (3 drops/day); CP - castrated/placebo and SP - Sham/placebo that received 3 drops/day of distilled water. The animals were sacrificed at seven, fourteen and twenty-eight days after the beginning of treatment and had their tibiae removed. The tibiae's digital XR was analyzed in order to evaluate optical density, using the Image Tool program. Then, they were decalcified and processed for histologic analysis. Histomorphometric measures of bone percentual formation were evaluated using a graticule in the central area of the lesion, with the Image J program. Data was submitted to ANOVA, Tukey and Dunnett tests (5% level). According to the optical density, the CCp group showed the best results at seven and fourteen days, but it was surpassed by the CR group at the 28th day. The histomorphometrical analyses showed that the SP group had the best result at seven days but the CR group formed more bone than all the other groups at 14 and 28 days.Measuring the bony callus, the CR group had the thicker callus at seven and 28 days. It... Complete abstract, click electronic address below) / Mestre

Made available in DSpace on 2014-06-11T19:23:04Z (GMT). No. of bitstreams: 0 Previous issue date: 2005-07-26Bitstream added on 2014-06-13T18:09:15Z : No. of bitstreams: 1 werkman_c_me_sjc.pdf: 536599 bytes, checksum: 7def8f8672e76b8811df840d31139525 (MD5) / A osteoporose, doença caracterizada pela perda de massa óssea, tem sido alvo de estudos nos últimos anos. Fraturas decorrentes da osteoporose são muito comuns e podem apresentar consolidação mais lenta. O objetivo deste trabalho foi avaliar o efeito do risedronato (medicamento alopático) e da Calcarea phosphorica 6CH (medicamento homeopático) no processo de reparo ósseo em ratos machos com osteoporose induzida por castração. Para tanto, foram utilizados oitenta e quatro ratos de três meses de idade separados em quatro grupos de vinte e um animais, sendo três grupos submetidos à castração e um grupo a falsa cirurgia (sham). Um mês após, foram realizadas lesões ósseas monocorticais na tíbia de todos os animais e a partir do dia seguinte, os respectivos tratamentos foram iniciados de acordo com os seguintes grupos: CR - castrado/ risedronato (1mg/kg/dia); CCp - castrado/Calcarea phosphorica 6CH (três gotas/dia); CP - castrato/placebo e SP - sham/placebo que receberam apenas três gotas ao dia de água destilada. Os animais foram sacrificados aos sete, catorze e vinte e oito dias após o início do tratamento e as tíbias removidas. Radiografias digitais foram realizadas e avaliadas pelo programa Image Tool para obter a densidade óptica na área do defeito. Então as tíbias foram descalcificadas e processadas para a realização das análises histológicas. A histomorfometria mediu a porcentagem de osso formado utilizando um retículo graduado colocado no centro da lesão através do programa Image J. Para a análise estatística, os dados foram submetidos aos testes de ANOVA, Tukey e Dunnett, ao nível de 5%. Segundo a análise da densidade óptica, o grupo CCp apresentou os melhores resultados aos sete e catorze dias, mas foi superado pelo grupo CR aos vinte e oito dias. Segundo a histomorfometria o grupo SP apresentou o melhor resultado aos sete dias,... / Osteoporosis, a disease characterized by progressive bone loss, has been the target of several studies lately. It results in a much higher risk for fractures and might cause slower bone consolidation. The aim of this work was to study the effects of Risedronate (allopathic medicine) and Calcarea phosphorica 6CH (homeopathic medicine) to repair bone lesions in male rats with osteoporosis, induced by castration. For this, eighty-four three-months-old rats were used divided in four groups of twenty-one animals. Three groups where castrated and one group was submitted to Sham surgery. One month later, monocortical lesions were made in all animals' tibiae and after one day they began the different treatments according to the following groups: CR - castrated/Risedronate (1mg/kg/day); CCp - castrated/Calcarea phosphorica 6CH (3 drops/day); CP - castrated/placebo and SP - Sham/placebo that received 3 drops/day of distilled water. The animals were sacrificed at seven, fourteen and twenty-eight days after the beginning of treatment and had their tibiae removed. The tibiae's digital XR was analyzed in order to evaluate optical density, using the Image Tool program. Then, they were decalcified and processed for histologic analysis. Histomorphometric measures of bone percentual formation were evaluated using a graticule in the central area of the lesion, with the Image J program. Data was submitted to ANOVA, Tukey and Dunnett tests (5% level). According to the optical density, the CCp group showed the best results at seven and fourteen days, but it was surpassed by the CR group at the 28th day. The histomorphometrical analyses showed that the SP group had the best result at seven days but the CR group formed more bone than all the other groups at 14 and 28 days.Measuring the bony callus, the CR group had the thicker callus at seven and 28 days. It... Complete abstract, click electronic address below)