Chitosan conduits filled with simvastatin/Pluronic F‐127 hydrogel promote peripheral nerve regeneration in rats

Abstract

Treating peripheral nerve defects represents a clinical challenge, and nerve conduits lacking an internal scaffold lead to limited large nerve gap regeneration. Here, we bridged 10-mm sciatic nerve defects in rats with a chitosan conduit filled with 0, 0.5, or 1.0 mg of simvastatin in Pluronic F-127 hydrogel. We assessed subsequent nerve regeneration using the sciatic functional index (SFI), electrophysiological assessments, Fluoro-Gold (FG) retrograde tracing, gastrocnemius muscle mass measurements, and histological and immunohistochemical assessments of nerve regeneration. Ten weeks after implantation, the chitosan conduit filled with simvastatin/Pluronic F-127 hydrogel promoted nerve regeneration; there were significant increases in the SFI, compound muscle action potential peak amplitude, motor nerve conduction velocity, FG-labeled neuron number in the dorsal root ganglia, myelin sheath thickness, axon diameter, gastrocnemius wet weight, and muscle fiber area percentage in the gastrocnemius muscle (all p < 0.05). The expression levels of neurotrophic factors, such as pleiotrophin, hepatocyte growth factor, vascular endothelial growth factor, and glial cell line-derived neurotrophic factor, were also found to be increased. The results suggest that chitosan conduits filled with simvastatin/Pluronic F-127 hydrogel improved peripheral nerve regeneration and functional recovery in rats, which may have been related to the increased expression of several endogenous neurotrophic factors. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 787-799, 2018.

The advances in nerve tissue engineering: From fabrication of nerve conduit toin vivonerve regeneration assays

“…For example, Yuan, Zhang, Yang, Wang, and Gu () have shown that chitosan fibers support the adhesion, migration, and proliferation of SCs that result in axonal regeneration in the PNS. Various studies have demonstrated that transplantation of chitosan‐based nerve conduits in 1‐cm gaps or more with or without cells in the rat nerve repair models can induce nerve regeneration and repair damaged nerve (Fregnan et al, ; Guo et al, ; Meyer et al, ; Ruini et al, ; Yin et al, ). A recent study has also reported that chitosan conduits filled with simvastatin/Pluronic F‐127 hydrogel promote peripheral nerve regeneration and motor functional recovery in rats with 10‐mm sciatic nerve defects (Guo et al, ).…”

Hydrogels based on chitosan in tissue regeneration: How do they work? A mini review

“…For example, steroids like methylprednisolone were incorporated into chitosan‐based conduits to treat facial nerve injury due to the anti‐edema and anti‐inflammatory effect . Simvastatin is a cholesterol‐lowering drug that can improve neurological disabilities if delivered by chitosan‐based conduits because of their anti‐inflammatory, antioxidant, immunomodulatory, and neuroprotective pleiotropic effects . The last category of drugs is the growth factor.…”

Simvastatin vs. l-carnitine: an experimental study on optimizing nerve repair

“…Here, the greatest neural bundle differentiation was observed in simvastatin one-month group (SIM1M) followed by L-carnitine one-month group (LC1M), but this difference was significant only in SIM1M group compared to the others. This can be due to participation of simvastatin in molecular up-regulation (12), and its probable synergistic effect with SCs by stimulating them to secrete NGFs (15). It is known that lipid and cholesterol metabolism is vital for neuron viability during development and also degenerative diseases (18,43).…”