Electrodeposition of chitosan/graphene oxide conduit to enhance peripheral nerve regeneration.

Currently available commercial nerve guidance conduits have been applied in the repair of peripheral nerve defects. However, a conduit exhibiting good biocompatibility remains to be developed. In this work, a series of chitosan/graphene oxide (GO) films with concentrations of GO varying from 0-1 wt% (collectively referred to as CHGF-n) were prepared by an electrodeposition technique. The effects of CHGF-n on proliferation and adhesion abilities of Schwann cells were evaluated. The results showed that Schwann cells exhibited elongated spindle shapes and upregulated expression of nerve regeneration-related factors such as Krox20 (a key myelination factor), Zeb2 (essential for Schwann cell differentiation, myelination, and nerve repair), and transforming growth factor ß (a cytokine with regenerative functions). In addition, a nerve guidance conduit with a GO content of 0.25% (CHGFC-0.25) was implanted to repair a 10-mm sciatic nerve defect in rats. The results indicated improvements in sciatic functional index, electrophysiology, and sciatic nerve and gastrocnemius muscle histology compared with the CHGFC-0 group, and similar outcomes to the autograft group. In conclusion, we provide a candidate method for the repair of peripheral nerve defects using free-standing chitosan/GO nerve conduits produced by electrodeposition.

Gene delivery of chitosan-graft-polyethyleneimine vectors loaded on scaffolds for nerve regeneration.

As an important transcription factor, c-Jun could upregulate growth factors expression in Schwann cells (SCs). Arginine-Glycine-Aspartate (RGD)-functionalized chitosan-graft-polyethyleneimine (RCP) gene vectors were prepared through the maleic anhydride & the carbodiimide methods, and electrostatically bound with c-Jun plasmids (pJUN), finally loaded on poly-L-lactic acid/silk fibroin parallel fiber films to fabricate nerve scaffold (RCP/pJUN-PSPF@PGA), which could locally deliver c-Jun plasmids into SCs via the mediation of RGD peptides, and upregulate the expression of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in SCs. After the scaffold was bridged in sciatic nerve defect, the delivery of c-Jun plasmids from RCP/pJUN-PSPF@PGA facilitated SCs to sustain the expressions of NGF, BDNF and vascular endothelial growth factor in the injury field, promoting myelination, axonal growth and microvascular generation and nerve regeneration, muscle reinnervation and functional recovery. These results suggested that RCP/pDNA-PSPF@PGA, as an effective gene delivery platform, could provide a local gene therapy to improve nerve regeneration.

The engine initiating tissue regeneration: does a common mechanism exist during evolution?

A successful tissue regeneration is a very complex process that requires a precise coordination of many molecular, cellular and physiological events. One of the critical steps is to convert the injury signals into regeneration signals to initiate tissue regeneration. Although many efforts have been made to investigate the mechanisms triggering tissue regeneration, the fundamental questions remain unresolved. One of the major obstacles is that the injury and the initiation of regeneration are two highly coupled processes and hard to separate from one another. In this article, we review the major events occurring at the early injury/regeneration stage in a range of species, and discuss the possible common mechanisms during initiation of tissue regeneration.