Progress and mechanism of graphene oxide-composited materials in application of peripheral nerve repair.

Peripheral nerve injuries (PNI) are one of the most common nerve injuries, and graphene oxide (GO) has demonstrated significant potential in the treatment of PNI. GO could enhance the proliferation, adhesion, migration, and differentiation of neuronal cells by upregulating the expression of relevant proteins, and regulate the angiogenesis process and immune response. Therefore, GO is a suitable additional component for fabricating artificial nerve scaffolds (ANS), in which the slight addition of GO could improve the physicochemical performance of the matrix materials, through hydrogen bonds and electrostatic attraction. GO-composited ANS can increase the expression of nerve regeneration-associated genes and factors, promoting angiogenesis by activating the RAS/MAPK and AKT-eNOS-VEGF signaling pathway, respectively. Moreover, GO could be metabolized and excreted from the body through the pathway of peroxidase degradation in vivo. Consequently, the application of GO in PNI regeneration exhibits significant potential for transitioning from laboratory research to clinical use.

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.

Bimetal metal-organic framework domino micro-reactor for synergistic antibacterial starvation/chemodynamic therapy and robust wound healing.

Antibacterial chemodynamic therapy (aCDT) has captured considerable attention in the treatment of pathogen-induced infections due to its potential to inactivate bacteria through germicidal reactive oxygen species (ROS). However, the lifespan of ROS generated by CDT is too short to achieve the efficacy of complete sterilization; thus, residual bacteria inevitably reproduce and cause super-infections. To address this concern, we devise an innovative bimetal, metal-organic framework (BMOF) domino micro-reactor (BMOF-DMR), consisting of Cu/Zn-rich BMOF and glucose oxidase (GOx), via electrostatic self-assembly. GOx catalyzes conversion of glucose into H2O2, and the Cu2+ ions then convert H2O2 into ˙OH to kill bacteria, thereby showing a domino effect. Accordingly, the BMOF-DMR not only blocks the nutrient/energy supply for bacteria, but also triggers a Fenton(-like) reaction and glutathione (GSH) depletion in a self-generating H2O2 microenvironment, all leading to high-efficiency bactericidal performance through synergistic starvation/chemodynamic therapy. Remarkably, in vitro and in vivo assessments demonstrate that the BMOF-DMR has superior cytocompatibility and exhibits robust ability to accelerate infectious full-thickness cutaneous regeneration through eradicating bacteria, promoting epithelialization of the wound beds and facilitating angiogenesis from the antibacterial activity and delivery of bimetal elements. The advantage of this antibacterial platform is that it suppresses bacterial metabolism by blocking the energy supply, which might prevent secondary infections from residual bacteria. As envisaged, the use of such a micro-reactor with starvation/chemodynamic therapy is a promising approach for combating bacterial skin wounds.

Growth Factor-Decorated Ti3 C2 MXene/MoS2 2D Bio-Heterojunctions with Quad-Channel Photonic Disinfection for Effective Regeneration of Bacteria-Invaded Cutaneous Tissue.

Phototherapy has recently emerged as a competent alternative for combating bacterial infection without antibiotic-resistance risk. However, owing to the bacterial endogenous antioxidative glutathione (GSH), the exogenous reactive oxygen species (ROS) generated by phototherapy can hardly behave desired antibacterial effect. To address the daunting issue, a quad-channel synergistic antibacterial nano-platform of Ti3 C2 MXene/MoS2 (MM) 2D bio-heterojunctions (2D bio-HJs) are devised and fabricated, which possess photothermal, photodynamic, peroxidase-like (POD-like), and glutathione oxidase-like properties. Under near-infrared (NIR) laser exposure, the 2D bio-HJs both yield localized heating and raise extracellular ROS level, leading to bacterial inactivation. Synchronously, Mo4+ ions can easily invade into ruptured bacterial membrane, arouse intracellular ROS, and deplete intracellular GSH. Squeezed between the "ROS hurricane" from both internal and external sides, the bacteria are hugely slaughtered. After being further loaded with fibroblast growth factor-21 (FGF21), the 2D bio-HJs exhibit benign cytocompatibility and boost cell migration in vitro. Notably, the in vivo evaluations employing a mouse-infected wound model demonstrate the excellent photonic disinfection towards bacterial infection and accelerated wound healing. Overall, this work provides a powerful nano-platform for the effective regeneration of bacteria-invaded cutaneous tissue using 2D bio-HJs.