Lin Huang,Xiaqing Yang,Linglong Deng,Daofa Ying,Ang Lu,Lina Zhang,Aixi Yu,Bo Duan
The nerve guidance conduit (NGC) is a promising clinical strategy for regenerating the critical-sized peripheral nerve injury. In this study, the polysaccharide chitin is used to fabricate the hydrogel film for inducing the impaired sciatic nerve regeneration through incorporating the conductive poly(3,4-ethylenedioxythiophene) nanoparticles (PEDOT NPs) and modifying with cell adhesive tetrapeptide Cys–Arg–Gly–Asp (CRGD) (ChT-PEDOT-p). The partial deacetylation process of chitin for exposing the amino groups is performed to (i) improve the electrostatic interaction between chitin and the negatively charged PEDOT for enhancing the composite hydrogel strength and (ii) offer the active sites for peptide modification. The as-prepared hydrogel remarkably promotes the in vitro RSC-96 cell adhesion and proliferation, as well as the Schwann cell activity-related gene S100, NF-200, and myelin basic protein (MBP) expression. Function of gastrocnemius muscle and thickness of myelinated axon in chitin/PEDOT groups are analogous to the autograft in 10 mm rat sciatic nerve defect. Immunofluorescence, immunohistochemistry, western blotting, and toluidine blue staining analyses on the regenerated sciatic nerve explain that the attachment and proliferation enhancement of Schwann cells and angiogenesis are the vital factors for the chitin/PEDOT composite to facilitate the nerve regeneration. This work provides an applicable chitin-based NGC material for accelerating the peripheral nerve restoration.
Yitong Yuan,Miaomiao Xu,Limin Feng,Wanting Zhong,Longzhu Zhang,Ruochen Du,Jingjing Sun,Chunfang Wang,Jiangfeng Du
Inhibiting secondary cell death and promoting neuronal regeneration are critical for nerve repair after spinal cord injury (SCI). The excessive accumulation of reactive oxygen species (ROS) after SCI causes cell death and induces apoptosis. These reactions further increase the level of ROS production, leading to a vicious cycle of spinal cord tissue damage. Therefore, intervention targeting ROS is a potential therapeutic approach to improve the recovery of locomotor function after SCI. In this study, we designed and synthesized a nanozyme hydrogel delivery system loaded with multiple drugs, LA/Me/Se NPs-h. LA/Me/Se NPs-h exhibited a satisfactory size distribution and excellent stability, enhancing the bioavailability of therapeutic drugs. Moreover, we explored the antioxidant and protective effects of LA/Me/Se NPs-h against oxidative stress-induced cell damage caused by ROS production after SCI in vitro. In the mice SCI model, the Basso mouse scale and gait analysis showed that LA/Me/Se NPs-h significantly promoted the recovery of locomotor function after SCI. The histological and immunofluorescence results of the injury site revealed that LA/Me/Se NPs-h upregulated the expression of GFAP, NF-200, and superoxide dismutase in spinal cord lesion, reduced caspase-3 expression, improved spinal cord continuity, reduced lesion cavity, and inhibited the axonal demyelination. Consequently, LA/Me/Se NPs-h increased the activity of antioxidant enzymes and reduced neuronal apoptosis by reducing oxidative stress and ultimately promoted nerve regeneration. Taken together, this study demonstrated promising nanozyme hydrogels and provided an effective therapeutic strategy for SCI and other ROS-related diseases.
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