FK506-loaded chitosan conduit promotes the regeneration of injured sciatic nerves in the rat through the upregulation of brain-derived neurotrophic factor and TrkB

Zhao, Jia; Zheng, Xifu; Fu, Chongyang; Qü, Wei; Wei, Guoqiang; Zhang, Weiguo

doi:10.1016/j.jns.2014.06.005

Cited by 18 publications

(8 citation statements)

References 21 publications

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“…Hollow chitosan conduits were prepared as previously described with limited modifications . In brief, chitosan powder (Golden‐Shell Pharmaceutical, Zhejiang, China) was first dissolved in 8% (w/v) acetic acid.…”

Section: Methodsmentioning

confidence: 99%

“…Hollow chitosan conduits were prepared as previously described with limited modifications. 32,33 In brief, chitosan powder (Golden-Shell Pharmaceutical, Zhejiang, China) was first dissolved in 8% (w/v) acetic acid. Then, a 1.6-mmdiameter glass rod was vertically immersed in the chitosan solution and drawn out vertically until the outer diameter reached 2.0 mm.…”

Section: Preparation Of Hollow Chitosan Conduits and The Injectable Tmentioning

confidence: 99%

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

et al. 2017

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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.

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Section: Methodsmentioning

confidence: 99%

Section: Preparation Of Hollow Chitosan Conduits and The Injectable Tmentioning

confidence: 99%

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

et al. 2017

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“…The TON animal model was prepared by clamping the optic nerve (2 mm postocular) for 30 s with reverse artery-clamp. A liquid (200 lL) containing 1% of CS, 1.76 lg/ mL of FK506 (in micelle) (Zhao et al, 2014), 2 lg/mL of CNTF (Laughter et al, 2018), and b-GP was smeared at the injured site of optic nerve, and gelled under physiology temperature forming a sheet acting as a in situ drug depot for the sustainable drug release at the injured site of optic nerve. The retina, optic nerve, and RGC was evaluated on the 14 th day after the surgical procedure.…”

Section: In Vivo Post Ton Rgc Protective Effectsmentioning

confidence: 99%

Localized co-delivery of CNTF and FK506 using a thermosensitive hydrogel for retina ganglion cells protection after traumatic optic nerve injury

et al. 2020

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Following the traumatic axonal injury in the optic nerve, the failure of retrograde axonal transport to continuously supply neurotrophins from the brain to retina results in deprivation of neurotrophins in retinal ganglion cells (RGCs), which in turn can modulate the fate of RGCs toward apoptosis and thereby impede axon regeneration. In this study, a ciliary neurotrophic factor (CNTF) loaded thermosensitive hydrogel was designed and developed as a localized drug depot to restore neurotrophins supply following axon injury. Besides, following traumatic axon injury, overactive immune responses cause neurotoxicity and induce scar formation which together constitutes the major hindrances for axon regeneration. Thus, the FK506, a hydrophobic macrolide immunosuppressant, was co-loaded into the hydrogel after encapsulating it into a polymeric micelle. The materials can undergo sol-to-gel transition within minutes under a physiological pH of 37 C. The release of drugs from the hydrogel exhibited a sustainable profile in vitro. The optic nerve was exposed by surgical procedure and the animal model was prepared by crushing the nerve with a reverse clamp. For the localized delivery to the optic nerve, a pre-hydrogel liquid containing chitosan, FK506 (in micelle), CNTF, and the gelling agent was directly smeared on the injured site, which gelled under physiological condition. This co-delivery system exhibited in vivo RGCs protective effect against the adverse effects caused by traumatic optic nerve injury, indicating the potential of this drug delivery system for effective optic nerve repair and this strategy may provide promising platforms for localized drug delivery in various other therapies.

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“…Furthermore, Zhao et al (2014) hypothesized that tacrolismus-loaded chitosan enhances peripheral nerve regeneration through modulation of the expression profiles of neurotrophic factors. To test this hypothesis, they loaded tacrolismus onto chitosan conduits and examined nerve regeneration of sciatic nerve injury in a rat model.…”

Section: Neuronal Regenerationmentioning

confidence: 99%

Chitin/Chitosan: Versatile Ecological, Industrial, and Biomedical Applications

Merzendorfer

Cohen

2019

Biologically-Inspired Systems

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Chitin is a linear polysaccharide of N-acetylglucosamine, which is highly abundant in nature and mainly produced by marine crustaceans. Chitosan is obtained by hydrolytic deacetylation. Both polysaccharides are renewable resources, simply and cost-effectively extracted from waste material of fish industry, mainly crab and shrimp shells. Research over the past five decades has revealed that chitosan, in particular, possesses unique and useful characteristics such as chemical versatility, polyelectrolyte properties, gel-and film-forming ability, high adsorption capacity, antimicrobial and antioxidative properties, low toxicity, and biocompatibility and biodegradability features. A plethora of chemical chitosan derivatives have been synthesized yielding improved materials with suggested or effective applications in water treatment, biosensor engineering, agriculture, food processing and storage, textile additives, cosmetics fabrication, and in veterinary and human medicine. The number of studies in this research field has exploded particularly during the last two decades. Here, we review recent advances in utilizing chitosan and chitosan derivatives in different technical, agricultural, and biomedical fields.

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FK506-loaded chitosan conduit promotes the regeneration of injured sciatic nerves in the rat through the upregulation of brain-derived neurotrophic factor and TrkB

Cited by 18 publications

References 21 publications

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

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

Localized co-delivery of CNTF and FK506 using a thermosensitive hydrogel for retina ganglion cells protection after traumatic optic nerve injury

Chitin/Chitosan: Versatile Ecological, Industrial, and Biomedical Applications

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