Mohanna, Pari-Naz; (2002) The bioengineering of nerve conduits. Doctoral thesis (M.D), UCL (University College London).

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Abstract

Poly-3-hydroxybutyrate (PHB) conduits are an alternative to nerve autografting and support regeneration across long nerve gaps, although to suboptimal levels. The aim of this study was to improve these results by combining PHB with glial growth factor (GGF), enhancing nerve regeneration by contact guidance and an improved trophic microenvironment. Two and 4cm gaps in the rabbit common peroneal nerve were bridged using PHB-GGF conduits. The rate and quantity of axonal and Schwann cell (SC) regeneration were assessed by quantitative immunohistochemistry at 21, 42 and 63 days, and compared to empty and alginate filled conduits. Addition of GGF improved axonal and SC regeneration, which was sustained up to 63 days independent of gap length. The distance and quantity of axonal regeneration were increased by up to 53% and 4317% respectively. At 120 days axonal and SC regeneration within the PHB-GGF grafts remained superior to the controls resulting in enhanced motor organ reinnervation, as was demonstrated by an improved recovery of muscle mass compared to the controls. In both the short and long term studies the alginate filled conduits resulted in regeneration inferior to both the GGF and empty tubes. As a result alginate fibres were assessed in vitro and in vivo as an alternative to alginate hydrogel with a potential to deliver GGF. However, regeneration in vivo in alginate fibre filled conduits was inferior to conduits filled with alginate hydrogel. Polyhydroxyalkatone (PHA) was also evaluated as a conduit material, as GGF linkage and release from its walls is a feasible option. Four different PHA configurations were used to bridge a 1cm rat sciatic nerve gap. All 4 PHA configurations, accelerated axonal regeneration rate to 1mm/day versus 0.7mm/day with PHB conduits and resulted in a quantity of axonal regeneration superior to that seen in the autograft repairs. In conclusion, GGF improves axonal and SC regeneration across short and long gaps through PHB conduits, but alginate hydrogel appears to limit the trophic effect of GGF. Alginate fibres provide no improvement, however alginate's limitations may be overcome and regeneration further improved by using PHA as a bioconstruct releasing GGF into the conduit microenvironment.

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