Publicação
Desenvolvimento de compósitos de base dextrano para regeneração óssea
| Resumo: | Nowadays, bone infections due to diseases or injuries are a major problem, and the existing methods to treat them present some gaps and have several associated problems. In the case of auto and allografts, the mains problems are lack of donors and the risk of infections. While, in the case of implants and bone substitutes, the rejection is the main obstacle. The field of Tissue Engineering presents alternatives, such as scaffolds, to promote regeneration of injured tissues. Despite the advantages of these materials, most of them have an invasive surgical procedure associated. In order to avoid these problems, the main focus of this thesis is the development of scaffolds for bone regeneration, in the form of injectable hydrogels, which allow the regeneration of bone as they degrade and do not involve invasive procedures. Throughout this work, injectable hydrogels will be developed based on two natural polymers, dextran and gelatin, along with the use of two inorganic compounds, calcium β-triphosphate and nanohydroxyapatite, to reinforce the mechanical properties. In order to understand the influence of some parameters on formulation, different compositions were tested, varying the amount of crosslinker and the presence of inorganic compounds in the polymeric matrix. The developed material was later characterized to evaluate the necessary requirements for the intended application. FTIR and NMR analysis were performed to chemically characterize the material and to verify the chemical modification of the polymers. Taking into account the requirements for the intended application, the swelling capacity of the material was evaluated, as well as its degradation in a simulated physiological environment. To evaluate the influence of the different composition materials in mechanical properties, compression tests were performed. Vancomycin was incorporated into the polymeric matrix to assist the regeneration process, and the drug release profile was evaluated. The biocompatibility of the material was evaluated through MTS assay, using osteoblasts. The results showed that the synthesis of dextran-based hydrogels was successful, unlike gelatin-based hydrogels. In general, the hydrogels presented a suitable degradability, about one month, which are in line with the average time of the bone regeneration process. The compression tests gave favourable values for Young’s modulus (200-300 kPa), however they showed come variability due to the geometry of the sample used in the analysis. The drug release profile showed an initial burst release of around 50-80%, which makes longstanding treatment difficult, but it can facilitate the prevention of infections in the initial period. Regarding the material’s biocompatible, the results obtained showed some cytotoxicity which could be associated with AAD. |
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| Autores principais: | Simão, Ana Filipa Gouveia |
| Assunto: | Dextrano Oxidado Gelatina Modificada Hidrogéis Injetáveis Regeneração Óssea Libertação de Fármaco Oxidized Dextran Modified Gelatin Injectable Hydrogels Bone Regeneration Drug Release |
| Ano: | 2021 |
| País: | Portugal |
| Tipo de documento: | dissertação de mestrado |
| Tipo de acesso: | acesso embargado |
| Instituição associada: | Universidade de Coimbra |
| Idioma: | português |
| Origem: | Estudo Geral - Universidade de Coimbra |
| Resumo: | Nowadays, bone infections due to diseases or injuries are a major problem, and the existing methods to treat them present some gaps and have several associated problems. In the case of auto and allografts, the mains problems are lack of donors and the risk of infections. While, in the case of implants and bone substitutes, the rejection is the main obstacle. The field of Tissue Engineering presents alternatives, such as scaffolds, to promote regeneration of injured tissues. Despite the advantages of these materials, most of them have an invasive surgical procedure associated. In order to avoid these problems, the main focus of this thesis is the development of scaffolds for bone regeneration, in the form of injectable hydrogels, which allow the regeneration of bone as they degrade and do not involve invasive procedures. Throughout this work, injectable hydrogels will be developed based on two natural polymers, dextran and gelatin, along with the use of two inorganic compounds, calcium β-triphosphate and nanohydroxyapatite, to reinforce the mechanical properties. In order to understand the influence of some parameters on formulation, different compositions were tested, varying the amount of crosslinker and the presence of inorganic compounds in the polymeric matrix. The developed material was later characterized to evaluate the necessary requirements for the intended application. FTIR and NMR analysis were performed to chemically characterize the material and to verify the chemical modification of the polymers. Taking into account the requirements for the intended application, the swelling capacity of the material was evaluated, as well as its degradation in a simulated physiological environment. To evaluate the influence of the different composition materials in mechanical properties, compression tests were performed. Vancomycin was incorporated into the polymeric matrix to assist the regeneration process, and the drug release profile was evaluated. The biocompatibility of the material was evaluated through MTS assay, using osteoblasts. The results showed that the synthesis of dextran-based hydrogels was successful, unlike gelatin-based hydrogels. In general, the hydrogels presented a suitable degradability, about one month, which are in line with the average time of the bone regeneration process. The compression tests gave favourable values for Young’s modulus (200-300 kPa), however they showed come variability due to the geometry of the sample used in the analysis. The drug release profile showed an initial burst release of around 50-80%, which makes longstanding treatment difficult, but it can facilitate the prevention of infections in the initial period. Regarding the material’s biocompatible, the results obtained showed some cytotoxicity which could be associated with AAD. |
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