Abstract
BackgroundPeripheral nerve injury is one common clinical disease worldwide, in which sciatic nerve is anatomically the most challenging to regenerate given its length and large cross-sectional area. For the present, autologous nerve grafting remains to be the most ideal strategy when treating with sciatic nerve injury. However, this method sacrifices healthy nerves and requires highly intensive surgery, still calling for other advanced alternatives for nerve grafting.ResultsIn this study, we utilized previously well-established gene delivery system to dually deliver plasmid DNA (pDNA) encoding vascular endothelial growth factor (VEGF) and nerve growth factor (NGF), exploring therapeutics for sciatic nerve injury. Low-molecular-weight branched polyethylenimine (bPEI) was constructed as the backbone structure of gene vectors, and it was further crosslinked to synthesize degradable polycations via the conjugation of dialdehydes. Potential synergistic effect between VEGF and NGF proteins were observed on rat sciatic nerve crush injury model in this study.ConclusionsWe concluded that dual delivery of plasmid VEGF and NGF as gene therapy could enhance sciatic nerve regeneration.
Highlights
Peripheral nerve injury is one common clinical disease worldwide, in which sciatic nerve is anatomi‐ cally the most challenging to regenerate given its length and large cross-sectional area
We investigated the gene therapy system on rat Schwann cells (RSC) and further established a sciatic nerve crush injury model on Sprague–Dawley (SD) rats
Particle sizes stabilized around 125 nm and there were no significant differences observed in particle size among polyplexes at different ratios, which indicates a robust and stable system
Summary
Peripheral nerve injury is one common clinical disease worldwide, in which sciatic nerve is anatomi‐ cally the most challenging to regenerate given its length and large cross-sectional area. Autologous nerve grafting remains to be the most ideal strategy when treating with sciatic nerve injury. After having an overview of reported studies on tissue-engineered nerve grafting, we found that most pre-clinical researches focused on the role of neurogenesis in the peripheral nerve recovery, while the angiogenesis effect of blood vessels were often ignored [11]. With the growth and regeneration of peripheral nerve, metabolic demands are urgently increasing, in which more oxygen and nutrients are needed for the supply, and more waste products need to be removed In this case, enough blood vessels are of much essence, to exchange nutrients and waste products with outer environment and maintain the viability of new regenerative nerves [16,17,18,19]. A hypothesis could be made that both revascularization and neurogenesis are significantly important for the regeneration and reconstruction of sciatic nerve injury [22, 24]
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