Publicação
Algae-origin Fucoidan on development of therapeutic approaches for Diabetes Mellitus
| Resumo: | Diabetes mellitus (DM) is a metabolic disorder that affects 450 million people worldwide, being the sixth most common cause of death. Therefore, it is crucial to develop new therapeutic strategies and relevant models for diabetes in order to accelerate the discovery of new treatments. In this perspective, marine origin polymers represent a relatively untapped source that can be used in the creation of platforms/models to attend these needs. Algae, for instance, synthesize sulfated polysaccharides with several bioactivity properties, which added to their structural role, open new avenues in biomaterials research. The main focus of this thesis consists in the demonstration of the potential of fucoidan on the development of therapeutic approaches for diabetes mellitus treatment. Fucoidan (Fu) is an underexploited sulfated polysaccharide extracted from brown algae, which has interesting chemical and biological properties. The major obstacle for using fucoidan on polymeric devices for biomedical applications is the higher solubility in water. In order to control the solubility of fucoidan in water and increase its processability, a chemical modification was studied, a methacrylation reaction, enabling its further gelation by photocrosslinking. Quasi-spherical hydrogel particles were thus prepared, supporting the culture of human pancreatic cells (1.1B4HP), as well as the sustained delivery of insulin. Moreover, alternative methodologies based in blends of fucoidan with other natural/synthetic polymers were also explored. In particular, attention was given to agarose, with attractive gelling properties mediated by temperature. The properties of the resulting hydrogel were assessed, envisaging its use on the encapsulation of pancreatic cells (1.1B4HP cells) as a system to protect those cells from the host immune system. As pancreatic cells and islets are highly vascularized, a platform device was developed based on fibrous meshes of PCL/fucoidan using airbrush technique, with capacity to promote angiogenesis. Additionally, the anti-oxidant effect of fucoidan on beta cells was also assessed, enabling to protect those cells from oxidative stress. This fucoidan was combined with alginate, developing hydrogels capable to support the encapsulation of pancreatic cells and islets with insulin secretion responsive to glucose concentration in medium. Altogether the results obtained under the scope of this thesis gave interesting insights on the use of the new fucoidan-based structures as functional biomaterials with a potential pivotal role for diabetes treatment. |
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| Autores principais: | Reys, Lara Priscila Lopes |
| Assunto: | Brown Algae Diabetes Mellitus Fucoidan Hydrogels Marine Biomaterials Algas castanhas Biomateriais Marinhos Hidrogéis Engenharia e Tecnologia::Outras Engenharias e Tecnologias |
| Ano: | 2021 |
| País: | Portugal |
| Tipo de documento: | tese de doutoramento |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade do Minho |
| Idioma: | inglês |
| Origem: | RepositóriUM - Universidade do Minho |
| Resumo: | Diabetes mellitus (DM) is a metabolic disorder that affects 450 million people worldwide, being the sixth most common cause of death. Therefore, it is crucial to develop new therapeutic strategies and relevant models for diabetes in order to accelerate the discovery of new treatments. In this perspective, marine origin polymers represent a relatively untapped source that can be used in the creation of platforms/models to attend these needs. Algae, for instance, synthesize sulfated polysaccharides with several bioactivity properties, which added to their structural role, open new avenues in biomaterials research. The main focus of this thesis consists in the demonstration of the potential of fucoidan on the development of therapeutic approaches for diabetes mellitus treatment. Fucoidan (Fu) is an underexploited sulfated polysaccharide extracted from brown algae, which has interesting chemical and biological properties. The major obstacle for using fucoidan on polymeric devices for biomedical applications is the higher solubility in water. In order to control the solubility of fucoidan in water and increase its processability, a chemical modification was studied, a methacrylation reaction, enabling its further gelation by photocrosslinking. Quasi-spherical hydrogel particles were thus prepared, supporting the culture of human pancreatic cells (1.1B4HP), as well as the sustained delivery of insulin. Moreover, alternative methodologies based in blends of fucoidan with other natural/synthetic polymers were also explored. In particular, attention was given to agarose, with attractive gelling properties mediated by temperature. The properties of the resulting hydrogel were assessed, envisaging its use on the encapsulation of pancreatic cells (1.1B4HP cells) as a system to protect those cells from the host immune system. As pancreatic cells and islets are highly vascularized, a platform device was developed based on fibrous meshes of PCL/fucoidan using airbrush technique, with capacity to promote angiogenesis. Additionally, the anti-oxidant effect of fucoidan on beta cells was also assessed, enabling to protect those cells from oxidative stress. This fucoidan was combined with alginate, developing hydrogels capable to support the encapsulation of pancreatic cells and islets with insulin secretion responsive to glucose concentration in medium. Altogether the results obtained under the scope of this thesis gave interesting insights on the use of the new fucoidan-based structures as functional biomaterials with a potential pivotal role for diabetes treatment. |
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