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Hidrogéis Injetáveis Reforçados por Nanofibras para Suporte de Carga no Nucleus Pulposus
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Dor na zona lombar das costas (DZL) é considerada uma das condições globais mais comuns, afetando cerca de 568 milhões de pessoas. Esta condição tem mais incidência em adultos, sendo, por isso, a maior causa mundial de incapacidade no trabalho. A degeneração do disco intervertebral (DIV), comummente iniciada no nucleus pulposus (NP), está diretamente ligada à condição mencionada. Para contornar este problema é comum proceder-se a métodos que não apresentam a capacidade de restaurar as funções e estrutura do DIV na íntegra. Neste projeto, pretende-se combater este problema através do desenvolvimento de um sistema pouco invasivo baseado num hidrogel injetável termossensível à base de quitosano (CS) reforçado por nanofibras derivadas de biopolímeros capaz de devolver as funções e a estrutura ao NP danificado.
O sistema desenvolvido foi caracterizado segundo várias vertentes, tendo sido estudadas amostras que variavam em percentagem de celulose nanocristalina (CNC) (1,2,3 e 4% (m/m)) e de β-Glicerofosfato (β-GP) (5, 6 e 9% (m/m)). Conseguimos demonstrar, através de ensaios reológicos, que a adição de β-GP e CNCs como reforço nos permitiu obter um sistema termossensível capaz de gelificar a temperaturas entre 20 e 37 ºC e, através de ensaios de absorção, que as amostras apresentam capacidades de absorção máxima, quando em PBS a 37 ºC, entre cerca de 500% a 2100% do seu peso seco. Realizando ensaios de compressão não confinados, estes hidrogéis apresentam propriedades mecânicas promissoras para a mimetização de um NP saudável, compreendendo valores de módulo de Young entre cerca de 9 e 19 kPa. Resultados obtidos em microscopia eletrónica de varrimento (MEV) demonstraram uma estrutura microporosa muito complexa a diferentes escalas, através de ensaios de citotoxicidade com células VERO, provou-se que se obtiveram amostras não citotóxicas.
Ainda que seja necessário estudar com maior profundidade estes sistemas, os resultados obtidos até ao momento são bastante promissores para o que pode ser o estado preliminar de uma solução para a cura da maior causa mundial de incapacidade no trabalho, a DZL.
Low back pain (LBP) is considered one of the most common global conditions, affecting around 568 million people. This condition has a higher incidence in adults and is therefore the world's leading cause of incapacity for work. Degeneration of the intervertebral disc (IVD), which commonly begins in the nucleus pulposus (NP), is directly linked to this condition. To overcome this problem, it is common to use methods that do not have the capacity to restore the functions and structure of the IVD in its entirety. The aim of this project is to combat this problem by developing a non-invasive system based on a thermosensitive injectable hydrogel based on chitosan (CS) reinforced with nanofibers derived from biopolymers capable of restoring the functions and structure of the damaged NP. The system developed was characterized in various ways, with samples varying in the percentage of nanocrystalline cellulose (CNC) (1, 2, 3 and 4% (m/m)) and β-Glycerophosphate (β-GP) (5, 6 and 9% (m/m)) being studied. We were able to demonstrate, through rheological tests, that the addition of β-GP and CNCs as reinforcement allowed us to obtain a thermosensitive system capable of gelling at temperatures between 20 and 37 ºC and, through swelling tests, that the samples have maximum absorption capacities, when in PBS at 37 ºC, of between 500% and 2100% of their dry weight. In unconfined compression tests, these hydrogels showed promising mechanical properties for mimicking a healthy NP, with Young's modulus values between 9 and 19 kPa. Scanning electron microscopy (SEM) results showed a very complex microporous structure at different scales, and cytotoxicity tests with VERO cells proved that non-cytotoxic samples were obtained. Although these systems need to be studied in greater depth, the results obtained so far are very promising for what could be the preliminary stage of a solution for curing the world's biggest cause of incapacity at work, LBP.
Low back pain (LBP) is considered one of the most common global conditions, affecting around 568 million people. This condition has a higher incidence in adults and is therefore the world's leading cause of incapacity for work. Degeneration of the intervertebral disc (IVD), which commonly begins in the nucleus pulposus (NP), is directly linked to this condition. To overcome this problem, it is common to use methods that do not have the capacity to restore the functions and structure of the IVD in its entirety. The aim of this project is to combat this problem by developing a non-invasive system based on a thermosensitive injectable hydrogel based on chitosan (CS) reinforced with nanofibers derived from biopolymers capable of restoring the functions and structure of the damaged NP. The system developed was characterized in various ways, with samples varying in the percentage of nanocrystalline cellulose (CNC) (1, 2, 3 and 4% (m/m)) and β-Glycerophosphate (β-GP) (5, 6 and 9% (m/m)) being studied. We were able to demonstrate, through rheological tests, that the addition of β-GP and CNCs as reinforcement allowed us to obtain a thermosensitive system capable of gelling at temperatures between 20 and 37 ºC and, through swelling tests, that the samples have maximum absorption capacities, when in PBS at 37 ºC, of between 500% and 2100% of their dry weight. In unconfined compression tests, these hydrogels showed promising mechanical properties for mimicking a healthy NP, with Young's modulus values between 9 and 19 kPa. Scanning electron microscopy (SEM) results showed a very complex microporous structure at different scales, and cytotoxicity tests with VERO cells proved that non-cytotoxic samples were obtained. Although these systems need to be studied in greater depth, the results obtained so far are very promising for what could be the preliminary stage of a solution for curing the world's biggest cause of incapacity at work, LBP.
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Hidrogel Injetável Termossensível CNCs Quitosano β-GP