Ahmed, Zubair; (1998) Peripheral nerve regeneration on fibronectin fibre substrates. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Peripheral nerve injuries commonly result in a surgically irreducible gap and represent a serious problem in surgery. Clinically, autologous nerve grafts are the most effective means of promoting axonal regeneration across the space, but normally produce donor site morbidity. Other variations of experimental models have been used with the aim of directing rapid nerve regeneration, including entubation, artery and vein grafts and Millipore. However, each of these have significant limitations which affect complete regrowth. Fibronectin (Fn), a large extracellular matrix cell adhesion glycoprotein has been made into three-dimensional mats with a predominant fibre direction and shown to successfully enhance peripheral nerve regeneration in a rat model. The aim of this study was to identify the main features of Fn-implants which are important for rapid nerve repair. This involved testing implanted versions of Fn-mat from rat and monkey models, assessment of cell-matrix interaction in vitro and modification of Fn-materials by chemical and growth factor addition. The results from this study show that new materials can be made from fibronectin which have a potential use in repair of long peripheral nerve lesions. These fibronectin-based materials may be stabilised with micromolar concentrations of copper and zinc which also support strong growth of Schwann cells within these materials in culture. Fibronectin mats may also be soaked with neurotrophins to enhance nerve cell survival and enhance nerve regeneration. The speed of Schwann cell migration and alignment (upto 50 μm away from the original fibre) was increased. Migration speed was further enhanced when the fibres were treated with micromolar concentrations of copper or made, with a substantial content of fibrinogen (optimum 50:50). Taken together, all these results suggest a first design for an ideal conduit material for peripheral nerve repair. This would be (a) dimensions (fibrous), (b) fibre orientation (c) 50:50 fibronectin: fibrinogen, (d) treated with micromolar concentrations of copper, (e) seeded with Schwann cells in culture, and (f) soaked with a 'cocktail' of neurotrophic growth factors including nerve growth factor and neurotrophin-3.

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