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Bioadhesive materials for spinal cord regeneration

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Summary:Spinal cord injury (SCI) remains one of the most challenging conditions in regenerative medicine as current clinical approaches often fail to promote effective functional recovery and only delay the pathology progression. Tissue engineering offers a promising solution to overcome this challenge by the development of bioconstructs that can fill the injury site and promote tissue regeneration. A critical aspect of this approach is the adhesion of the construct to the injury site, followed by integration with the host tissue. In this thesis, bioadhesives for soft tissue regeneration, with particular emphasis on spinal cord repair, were developed and characterized. Natural polymers, namely collagen (Chapter III), fucoidan (Chapter IV), hyaluronan (Chapter V and VI), and chitosan (Chapter VII and VIII) were functionalized using a biomimicking approach inspired by the underwater adhesion of marine mussels - functionalization with catechol groups was performed by different synthetic routes. This functionalization improved the adhesive and mechanical properties of the used biopolymers without compromising their biocompatibility, as shown by the enhanced cell viability and metabolic activity of the L929 fibroblast cell line (Chapters IIIIV). Biofunctionality was also improved: SH-SY5Y neuroblastoma cell line in contact with the modified materials expressed the neuronal marker β-III tubulin, indicating the capacity of these materials to support neuronal cell development (Chapters V, VI, and VII). Additionally, the bioadhesive hydrogels can serve as delivery vehicles, e.g. for antibodies, without compromising the mechanical properties, adhesiveness, injectability or self-healing characteristics (Chapter V). The importance of electrical conductivity in the context of spinal cord repair was also addressed in this thesis (Chapter VI): conductive bioadhesive hydrogels were developed and revealed to effectively mimic the native microenvironment of spinal cord tissue when subjected to electrical stimulation, thus, offering a promising approach to neural signal transmission. The therapeutic potential of the used biomimicking approach was validated ex vivo using mice spinal cords (Chapters V, VI, and VII) and in vivo (Chapter VIII): wounds treated with bioadhesives exhibited significantly accelerated healing, characterized by reduced wound size and controlled inflammatory response. These results demonstrated that the tissue-adhesive biomaterials developed under this thesis are sustainable therapeutic alternatives for soft tissue engineering, particularly in the context of spinal cord repair.
Main Authors:Correia, Cátia Sofia Palma
Subject:Bioadhesive materials Marine-derived polymers Spinal cord Neuroregeneration Materiais bioadesivos Polímeros de origem marinha Medula espinhal Neuro-regeneração
Year:2025
Country:Portugal
Document type:doctoral thesis
Access type:embargoed access
Associated institution:Universidade do Minho
Language:English
Origin:RepositóriUM - Universidade do Minho

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