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Hidrogel Compósito de Polímero/Nanofibras de Base Biológica para Aplicações Biomédicas
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A degeneração do disco intervertebral (DIV), muitas vezes iniciada no núcleo pulposo (NP), está associada à dor lombar, que é uma das principais causas de incapacidade a nível mundial e afeta 80% da população mundial. O tratamento desta condição é um desafio, pois os tratamentos atuais, limitam a capacidade do movimento do DIV e não apresentam a capacidade de restaurar a estrutura e as funções do DIV na totalidade. Neste trabalho, pretende-se desenvolver uma alternativa menos invasiva capaz de devolver as funções biomecânicas do NP danificado, como um hidrogel injetável à base de quitosano, caracterizado por ser um material compósito de biopolímeros, e que combine a reticulação via reações de base Schiff e as propriedades termorresponsivas de um LCST (Temperatura Inferior de Solubilidade Crítica), como a hidroxipropilcelulose oxidada (HPC-Ox).
Para tal foram testados vários sistemas, sendo o escolhido constituído por 2% quitosano, 2% celulose nanocristalina, 6% glicerofosfato e HPC-Ox (variável entre 2, 4 e 6% m/m). Através dos ensaios reológicos verificou-se que as ligações covalentes dominaram o sistema de reticulação, que o aumento de HPC-Ox aumenta as propriedades mecânicas, e apresentam curvas de viscosidades semelhantes às de um sistema líquido cristalino. Foi possível verificar que os hidrogéis apresentaram capacidades de absorção máximas, em solução tampão fosfato salina (PBS) a 37 ºC, entre 548 e 230%. Ensaios de compressão não confinados a 37 ºC nestes hidrogéis originaram módulos de Young médios de 17, 43 e 58 kPa, ou seja, apresentam propriedades mecânicas promissoras para imitar o NP saudável. A análise MEV demonstrou que estes hidrogéis apresentam estruturas porosas complexas e observar a organização helicoidal originária de fases líquidas cristalinas na parede dos poros.
Os resultados obtidos até ao momento são bastante promissores para a fase inicial de desenvolvimento deste novo sistema de hidrogel para aplicações biomédicas, tais como, o tratamento do NP.
Degeneration of the intervertebral disc (IVD), often beginning in the nucleus pulposus (NP), is associated with low back pain, which is one of the main causes of worldwide disability and affects 80% of the world's population. Treating this condition is a challenge, as current treatments limit the movement capacity of the IVD and do not have the capacity to restore the structure and functions of the IVD in its entirety. This study aims to develop a less invasive alternative capable of restoring the biomechanical functions of the damaged NP, such as an injectable chitosan-based hydrogel, characterized by being a biopolymer composite material, which combines cross-linking via Schiff base reactions and the thermoresponsive properties of an LCST (Low Critical Solution Temperature), such as hydroxypropyl cellulose oxidized (HPC-Ox). To achieve this goal, various systems were tested, with the chosen one consisting of 2% chitosan, 2% nanocrystalline cellulose, 6% glycerophosphate and HPC-Ox (varying between 2, 4 and 6% m/m). The rheological tests showed that covalent bonds dominated the crosslinking system, that the increase in HPC-Ox improved the mechanical properties and that the flow curves were similar to those of a liquid crystalline system. It was possible to verify that the hydrogels showed maximum absorption capacities, in phosphate buffered saline (PBS) at 37 ºC, of between 567 and 237%. Unconfined compression tests at 37 ºC on these hydrogels resulted in average Young's moduli of 17, 43 and 58 kPa, i.e. they have promising mechanical properties for imitating healthy NP. SEM analysis showed that these hydrogels have complex porous structures and observed the helical organization originating from liquid crystalline phases in the pore wall. The results obtained so far are very promising for the initial development phase of this new hydrogel system for biomedical applications, such as the treatment of NP.
Degeneration of the intervertebral disc (IVD), often beginning in the nucleus pulposus (NP), is associated with low back pain, which is one of the main causes of worldwide disability and affects 80% of the world's population. Treating this condition is a challenge, as current treatments limit the movement capacity of the IVD and do not have the capacity to restore the structure and functions of the IVD in its entirety. This study aims to develop a less invasive alternative capable of restoring the biomechanical functions of the damaged NP, such as an injectable chitosan-based hydrogel, characterized by being a biopolymer composite material, which combines cross-linking via Schiff base reactions and the thermoresponsive properties of an LCST (Low Critical Solution Temperature), such as hydroxypropyl cellulose oxidized (HPC-Ox). To achieve this goal, various systems were tested, with the chosen one consisting of 2% chitosan, 2% nanocrystalline cellulose, 6% glycerophosphate and HPC-Ox (varying between 2, 4 and 6% m/m). The rheological tests showed that covalent bonds dominated the crosslinking system, that the increase in HPC-Ox improved the mechanical properties and that the flow curves were similar to those of a liquid crystalline system. It was possible to verify that the hydrogels showed maximum absorption capacities, in phosphate buffered saline (PBS) at 37 ºC, of between 567 and 237%. Unconfined compression tests at 37 ºC on these hydrogels resulted in average Young's moduli of 17, 43 and 58 kPa, i.e. they have promising mechanical properties for imitating healthy NP. SEM analysis showed that these hydrogels have complex porous structures and observed the helical organization originating from liquid crystalline phases in the pore wall. The results obtained so far are very promising for the initial development phase of this new hydrogel system for biomedical applications, such as the treatment of NP.
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Hidrogel Quitosano HPC-Ox Base Schiff Sistema Líquido-cristalino