Despite the success of tissue engineered nerve guidance conduits (NGCs) for the treatment of small peripheral nerve injuries， autografts remain the clinical gold standard for larger injuries. The delivery of neurotrophic factors from conduits might enhance repair for more effective treatment of larger injuries but the efficacy of such systems is dependent on a safe， effective platform for controlled and localised therapeutic delivery. Gene therapy might offer an innovative approach to control the timing， release and level of neurotrophic factor production by directing cells to transiently sustain therapeutic protein production in situ. In this study， a gene-activated NGC was developed by incorporating n... More
Despite the success of tissue engineered nerve guidance conduits (NGCs) for the treatment of small peripheral nerve injuries， autografts remain the clinical gold standard for larger injuries. The delivery of neurotrophic factors from conduits might enhance repair for more effective treatment of larger injuries but the efficacy of such systems is dependent on a safe， effective platform for controlled and localised therapeutic delivery. Gene therapy might offer an innovative approach to control the timing， release and level of neurotrophic factor production by directing cells to transiently sustain therapeutic protein production in situ. In this study， a gene-activated NGC was developed by incorporating non-viral polyethyleneimine-plasmid DNA (PEI-pDNA) nanoparticles (N/P 7 ratio， 2 μg dose) with the pDNA encoding for nerve growth factor (NGF)， glial derived neurotrophic factor (GDNF) or the transcription factor c-Jun. The physicochemical properties of PEI-pDNA nanoparticles， morphology， size and charge， were shown to be suitable for gene delivery and demonstrated high Schwann cell transfection efficiency (60 ± 13%) in vitro. While all three genes showed therapeutic potential in terms of enhancing neurotrophic cytokine production while promoting neurite outgrowth， delivery of the gene encoding for c-Jun showed the greatest capacity to enhance regenerative cellular processes in vitro. Ultimately， this gene-activated NGC construct was shown to be capable of transfecting both Schwann cells (S42 cells) and neuronal cells (PC12 and dorsal root ganglia) in vitro， demonstrating potential for future therapeutic applications in vivo.
