[Animal experiment]-Chitosan catheter combined with simvastatin/poloxamer 407 hydrogel to repair peripheral nerve defects in rats

  Objective: To explore the feasibility of chitosan catheter combined with simvastatin/poloxamer 407 hydrogel as acellular artificial nerve scaffold to repair sciatic nerve defects.

  Method: prepare chitosan catheter and simvastatin/poloxamer 407 hydrogel, and observe the performance of composite material through stereo microscope, scanning electron microscope, in vitro degradation experiment, rheology test. Forty SPF SD rats were selected and divided into 4 groups: simple catheter group, catheter-containing simvastatin 0 mg group, catheter-containing simvastatin 0.5 mg group, and catheter-containing simvastatin 1 mg group. The first two groups are the control group. The latter two groups were simvastatin treatment groups, each with 10 rats, a 10 mm left sciatic nerve defect model was established, the defect was bridged with a chitosan catheter, and simvastatin hydrogel of different concentrations was filled. Ten weeks after transplantation, the middle part of the regenerated nerve was stained with HE, and the morphological changes of the regenerated nerve were observed with transmission electron microscope, and the number of regenerated nerve axons, myelin thickness, G ratio, etc. were analyzed statistically. Immunohistochemistry: Observe the expression of NF200 and S100 protein in regenerating nerve and the expression of neurotrophic factors PTN, HGF, GDNF and VEGF.

  Result: Chitosan catheter and Simvastatin/Poloxamer 407 hydrogel are cell-free repair materials and are suitable for nerve defects. Ten weeks after transplantation, nerve regeneration was seen in all four groups, but HE staining showed that the nerve trunk of the simvastatin treatment group was significantly thicker than the control group. In the simvastatin treatment group, transmission electron microscopy significantly increased the number of regenerated axons and significantly increased the number of myelin sheaths. In the degree of myelination, the thickness G ratio is also significantly better than the control group. Immunohistochemistry showed that the positive expression of NF200-labeled axons and S100-labeled Schwann cells in the simvastatin treatment group was significantly enhanced and endogenous. The sex neurotrophic factors PTN, HGF, VEGF and GDNF showed high expression .

  Conclusion: Chitosan catheter combined with simvastatin/poloxamer 407 hydrogel can significantly promote the histological reconstruction of nerve defects and can be used to repair sciatic nerve defects.