A biomaterials approach to peripheral nerve repair
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Peripheral nerve injuries are a major clinical problem which currently affect over one million people worldwide. Transection injuries caused by workplace and home injuries, road traffic accidents and by intentional harm lead to debilitating and painful injuries for those afflicted. Treatments are limited and largely ineffective. The patient's own donor nerve (autograft) is the gold standard for repair but this treatment is largely unsuccessful, suffering from limited supply with donor site morbidity and pain. The use of hollow nerve guidance conduits (NGCs) is the current clinically approved alternative. However these have shown limited applicability in the clinic. Thus, the objective of this thesis was to improve and understand the use of these hollow NGCs and attempt to improve functional nerve regeneration using the concept of intraluminal guidance. Intraluminal guidance involves the incorporation of biomaterial structures (in this instance extruded collagen fibres) to replace the natural fibrin cable which forms during repair and guide regenerating axons to their distal targets. An intraluminal collagen fibre conduit was tested across both a non-critical (10 mm) and critical nerve gap (15 mm) in a rat sciatic nerve model for its ability to promote repair. Through sequential studies, it was shown that the incorporation of intraluminal structure reduced the misdirection of regenerating axons during repair and also achieved functional regeneration in a number of parameters similar to that of the gold standard. Additionally, the intraluminal fibre conduit demonstrated the ability to regenerate across, the aforementioned, critical nerve gap (a nerve gap where regeneration is minimal if not absent). Based on these results, a further understanding of the early molecular mechanisms resulting in these beneficial effects was warranted. Using proteomics analysis the effect of the biomaterial used, the incorporation of intraluminal structure and the influence of increasing gap distance were documented. From this understanding, the key molecular components governing the increased nerve regeneration seen in the intraluminal fibre conduit and the robust regeneration seen within autograft were revealed. Based on the conclusions of this study, an intraluminal fibre conduit or a hollow biomaterial conduit may be further functionalised to match the molecular profile of the gold standard for repair.
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