Publicação
Combinatorial approaches for the development of conduits for guided peripheral nerve regeneration
| Resumo: | Regeneration, reconstruction and repair of peripheral nerve injuries (PNIs) are among the most complex and demanding challenges in the field of regenerative medicine. As a promising alternative to the “gold standard” autologous nerve grafts, tissue-engineered nerve guidance conduits (NGCs) have been extensively studied. However, in order to be able to produce an adequate NGC, the basic principles of neuro-biology must be known and followed. Also, great efforts have been made in terms of pre-clinical and clinical applications of engineered biomaterials for peripheral nerve regeneration. Furthermore, nanotechnology approaches have propelled nerve regenerative strategies. These themes are the focus of Section 1, in Chapters I, II and III. This PhD project has focused mainly on researching, developing and testing natural and biodegradable biomaterials using several fabrication methods to obtain the NGCs (Chapter IV). The first explored biomaterial was chitosan, in Chapter V, where the suitability of chitosan membranes with three different low degrees of acetylation was evaluated. Furthermore, to enhance the membranes’ cell adhesion and angiogenic properties, extracted human hair keratin was combined to the previous described membranes (Chapter VI). In Chapter VII, chitosan NGCs which are currently being used in in the clinical setting (Reaxon®), were used in combination with different gellan gum luminal fillers, mimicking the native Bands of Büngner. In Chapter VIII, a ground-breaking silk fibroin (SF) fabrication method for NGCs was established. SF NGCs were produced using a novel technology that comprises a horseradish peroxidase-mediated crosslinking system. Such innovative processing method resulted in the filling of an international patent. The excellent outcomes demonstrated by the enzymaticallycrosslinked method lead to an original research paper (Chapter IX). In line with the previous work, and because of its resourcefulness, a step forward was given, and a state-of-the-art study was performed, comprising the production of enzymatically-crosslinked SF NGCs capable of incorporating and delivering different neurotrophic factors. The developed NGCs restored the functional activity and enhanced neovascularization in the regenerated nerves, revealing comparable results to the autograft (Chapter X). In summary, the presented outcomes contributed to improve the actual state-of-art in what regards peripheral nerve regeneration, providing promising and versatile alternatives by using different types of natural-based biomaterials and approaches (Chapter XI). |
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| Autores principais: | Carvalho, Cristiana Rodrigues |
| Assunto: | Biomaterials Conduits Chitosan Gellan Gum Silk Fibroin Peripheral Nerve Biomateriais Fibroína da Seda Gellan Gum Quitosano Nervo Periférico |
| Ano: | 2019 |
| País: | Portugal |
| Tipo de documento: | tese de doutoramento |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade do Minho |
| Idioma: | português |
| Origem: | RepositóriUM - Universidade do Minho |
| Resumo: | Regeneration, reconstruction and repair of peripheral nerve injuries (PNIs) are among the most complex and demanding challenges in the field of regenerative medicine. As a promising alternative to the “gold standard” autologous nerve grafts, tissue-engineered nerve guidance conduits (NGCs) have been extensively studied. However, in order to be able to produce an adequate NGC, the basic principles of neuro-biology must be known and followed. Also, great efforts have been made in terms of pre-clinical and clinical applications of engineered biomaterials for peripheral nerve regeneration. Furthermore, nanotechnology approaches have propelled nerve regenerative strategies. These themes are the focus of Section 1, in Chapters I, II and III. This PhD project has focused mainly on researching, developing and testing natural and biodegradable biomaterials using several fabrication methods to obtain the NGCs (Chapter IV). The first explored biomaterial was chitosan, in Chapter V, where the suitability of chitosan membranes with three different low degrees of acetylation was evaluated. Furthermore, to enhance the membranes’ cell adhesion and angiogenic properties, extracted human hair keratin was combined to the previous described membranes (Chapter VI). In Chapter VII, chitosan NGCs which are currently being used in in the clinical setting (Reaxon®), were used in combination with different gellan gum luminal fillers, mimicking the native Bands of Büngner. In Chapter VIII, a ground-breaking silk fibroin (SF) fabrication method for NGCs was established. SF NGCs were produced using a novel technology that comprises a horseradish peroxidase-mediated crosslinking system. Such innovative processing method resulted in the filling of an international patent. The excellent outcomes demonstrated by the enzymaticallycrosslinked method lead to an original research paper (Chapter IX). In line with the previous work, and because of its resourcefulness, a step forward was given, and a state-of-the-art study was performed, comprising the production of enzymatically-crosslinked SF NGCs capable of incorporating and delivering different neurotrophic factors. The developed NGCs restored the functional activity and enhanced neovascularization in the regenerated nerves, revealing comparable results to the autograft (Chapter X). In summary, the presented outcomes contributed to improve the actual state-of-art in what regards peripheral nerve regeneration, providing promising and versatile alternatives by using different types of natural-based biomaterials and approaches (Chapter XI). |
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