Membranas híbridas do tipo ureasil-poliéter contendo glicose para futura aplicação em regeneração óssea
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Data
2022-01-18
Autores
Silva, Camila Garcia da
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Universidade Estadual Paulista (Unesp)
Resumo
Células-tronco mesenquimais (MSC - Mesenchymal stem cell) apresentam capacidade de diferenciar-se em diversas linhagens celulares, e desta maneira auxiliam no processo de regeneração de tecidos, incluindo o tecido ósseo. Porém, a aplicação das MSC apresenta resultados imprevisíveis devido à baixa sobrevida das células frente ao processo de isquemia, uma vez que a escassez de oxigênio e nutrientes promove estresse metabólico, diminuindo a sobrevida destas células. Sendo assim, neste trabalho foram desenvolvidas membranas poliméricas formadas por materiais híbridos orgânico-inorgânicos chamados ureasil-poliéter para liberação controlada de glicose com o objetivo do futuro uso em processos de regeneração óssea que necessitem da presença deste nutriente. Desta forma, a partir do método sol-gel, foram desenvolvidas membranas formadas pela mistura de polímeros, óxido de polipropileno (PPO4000) e óxido de polietileno (PEO500) com incorporação de 6% de glicose. Técnicas de caracterização físico-química foram realizadas, assim como a avaliação das propriedades térmicas, bioatividade, ensaio de intumescimento e de liberação do ativo em solução SBF, além da cinética de liberação a partir do modelo Korsmeyer-Peppas. Os resultados do teste de intumescimento mostraram que o aumento de massa das membranas ocorre com o acréscimo da concentração de ureasil-PEO500 na mistura. A análise mecânico dinâmica (DMA) mostrou que as membranas não sofreram ruptura, quando submetida à aplicação de uma elevada força de compressão (15 N). Os difratogramas de raios X (DRX) apresentaram picos alargados característicos das regiões amorfas do material híbrido e a ausência de picos de difração relacionados à glicose. As curvas de DSC também não apresentaram picos característicos da glicose, e a ausência de pico de fusão em todas as amostras corrobora com a característica amorfa do material, além de evidenciar a alta estabilidade térmica. O ângulo de contato menor para a membrana ureasil-PEO500 revelou o caráter mais hidrofílico do material em relação as outras membranas, atribuído ao caráter hidrofílico do precursor PEO500. As membranas apresentaram bioatividade in vitro e os resultados de pH da solução permaneceram dentro da faixa adequada para que não cause danos às células. O teste de liberação in vitro revelou que é possível modular o perfil e controlar a velocidade de liberação do ativo nas membranas preparadas a partir da mistura dos precursores ureasil PEO500/PPO4000. A análise cinética revelou mecanismo de liberação característico de cinética de transporte anômalo. Dessa forma, podemos concluir que as membranas ureasil-poliéter apresentam grande potencial para serem utilizadas como sistema de liberação de glicose, e futura aplicação no auxílio de regeneração óssea.
Mesenchymal stem cells (MSC) have the ability to differentiate into different cell lines, and in this way to assist in tissue regeneration process, including the bone tissue. However, the application of MSC has unpredictable results due to the low survival of cells against the ischemic process, since the lack of oxygen and nutrients promotes metabolic stress, decreasing the survival of these cells. Therefore, in this work polymeric membranes formed by organic-inorganic hybrid materials called ureasil-polyether for controlled release of glucose with the aim of future use in bone regeneration processes that need the presence of this nutriente were developed. From the sol-gel method, membranes formed by mixing polymers, polypropylene oxide (PPO4000) and polyethylene oxide (PEO500) with incorporation of 6% of glucose were developed. Physical chemical characterization techniques were performed, as well as the evaluation of thermal properties, bioactivity, swelling and active release test in SBF solution, in addition to the release kinetics from the Korsmeyer-Peppas model. The results of the swelling test showed that the increase in membrane mass occurs with the increase in the concentration of ureasil-PEO500 in the mixture. Dynamic mechanical analysis (DMA) showed that the membranes did not rupture when subjected to the application of a high compression force (15 N). X-ray diffractograms (XRD) showed broad peaks characteristics of the amorphous regions of the hybrid material and the absence of glucose-related diffraction peaks. The DSC curves did not show glucose peaks and the absence of melting peaks in all samples, also revealed the amorphous characteristic of the material, in addition to evidencing its high thermal stability. The smaller contact angle for the ureasil-PEO500 membrane revealed the more hydrophilic character of the material in relation to the other membranes, attributed to the hydrophilic character of the PEO500 precursor. The membranes showed in vitro bioactivity and the solution pH results remained within the proper range so that it does not cause damage to the cells. The in vitro release test revealed that it is possible to modulate the profile and control the release rate of the active in membranes prepared from the mixture of precursor’s ureasil-PEO500/PPO4000. Kinetic analysis revealed a release mechanism characteristic of anomalous transport kinetics. Thus, we can conclude that ureasyl-polyether membranes have great useful potential as a glucose release system, and future application to aid bone regeneration.
Mesenchymal stem cells (MSC) have the ability to differentiate into different cell lines, and in this way to assist in tissue regeneration process, including the bone tissue. However, the application of MSC has unpredictable results due to the low survival of cells against the ischemic process, since the lack of oxygen and nutrients promotes metabolic stress, decreasing the survival of these cells. Therefore, in this work polymeric membranes formed by organic-inorganic hybrid materials called ureasil-polyether for controlled release of glucose with the aim of future use in bone regeneration processes that need the presence of this nutriente were developed. From the sol-gel method, membranes formed by mixing polymers, polypropylene oxide (PPO4000) and polyethylene oxide (PEO500) with incorporation of 6% of glucose were developed. Physical chemical characterization techniques were performed, as well as the evaluation of thermal properties, bioactivity, swelling and active release test in SBF solution, in addition to the release kinetics from the Korsmeyer-Peppas model. The results of the swelling test showed that the increase in membrane mass occurs with the increase in the concentration of ureasil-PEO500 in the mixture. Dynamic mechanical analysis (DMA) showed that the membranes did not rupture when subjected to the application of a high compression force (15 N). X-ray diffractograms (XRD) showed broad peaks characteristics of the amorphous regions of the hybrid material and the absence of glucose-related diffraction peaks. The DSC curves did not show glucose peaks and the absence of melting peaks in all samples, also revealed the amorphous characteristic of the material, in addition to evidencing its high thermal stability. The smaller contact angle for the ureasil-PEO500 membrane revealed the more hydrophilic character of the material in relation to the other membranes, attributed to the hydrophilic character of the PEO500 precursor. The membranes showed in vitro bioactivity and the solution pH results remained within the proper range so that it does not cause damage to the cells. The in vitro release test revealed that it is possible to modulate the profile and control the release rate of the active in membranes prepared from the mixture of precursor’s ureasil-PEO500/PPO4000. Kinetic analysis revealed a release mechanism characteristic of anomalous transport kinetics. Thus, we can conclude that ureasyl-polyether membranes have great useful potential as a glucose release system, and future application to aid bone regeneration.
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Palavras-chave
Híbridos orgânico-inorgânicos, Processo sol-gel, Liberação de glicose, Regeneração óssea, Organic-inorganic hybrids, Sol-gel process, Glucose release, Bone regeneration