Hazari, Anita; (2000) Synthetic conduits and growth factors for improved peripheral nerve regeneration. Doctoral thesis (M.D), UCL (University College London).

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Abstract

Following trauma and loss of peripheral nerve tissue, an autologous nerve graft is the current gold standard for surgical repair. The alternative use of synthetic conduits has not yet offered suitable materials for wide clinical application. Two novel materials, poly-3-hydroxybutyrate (PHB) and polydioxanone (PDS), are bioresorbable and potentially useful as nerve conduits. The aim of this study was to examine peripheral nerve regeneration in vivo following grafting of PHB or PDS conduits, either alone or in combination with glial growth factor (GGF). Schwann cells are essential for nerve regeneration. GGF delivery to the injured nerve may increase their number within the graft and, indirectly enhance nerve regeneration. Nerve regeneration at the repair site was assessed by quantitative immunohistochemistry up to 1 year post-operatively. Centrally, primary sensory neuron survival and peripherally, target organ reinnervation were also studied morphologically following injury and repair. The use of PHB wrap-around for primary nerve repair was compared with direct epineural suture in the cat superficial radial nerve model. The two methods showed comparable values of axonal counts, diameter, myelin thickness and g-ratio. The results demonstrated that PHB wrap-around is a suitable alternative to epineural suture in primary repair. PHB tubes tested for nerve gap repair in the rat sciatic nerve model exhibited axonal regeneration comparable to that in nerve autografts. GGF administration in PHB tubes produced progressive increase of axonal growth with time, secondary to GGF-induced Schwann cell proliferation. PDS tubes also supported axonal regeneration, although these presented problems of material fragmentation and intense inflammatory reaction. Microgeometry of the internal surface of PDS tubes did not significantly improve nerve regeneration, peripheral target organ reinnervation or sensory neuron survival. The results of this study demonstrated PHB and PDS conduits sustain successful peripheral nerve regeneration, which can be further improved by targeted administration of growth factor.

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