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Introduction. Traumatic brain injury (TBI) remains a major cause of long-term neurological disability, affecting over 50 million individuals worldwide and imposing a global economic burden exceeding $400 billion.[1] TBI initiates acute neuronal and glial damage followed by chronic inflammatory and neurodegenerative cascades that impede recovery. Among the molecular regulators involved, dysregulated microRNAs (miRNAs), such as miR-21 and miR-155, amplify apoptotic and inflammatory signaling, leading to glial scarring, neuronal loss, and impaired regeneration.[2] Microporous annealed particulate scaffolds (MAPS) and flowable interlinked irregular particle (FLIP) hydrogels enable cell infiltration and immune modulation by mimicking the brain’s extracellular architecture. Incorporating cationic polymers and conductive nanomaterials within such scaffolds has been shown to enhance nucleic acid stability, transfection efficiency, and localized gene delivery.[3] In parallel, electromagnetic field (EMF)-induced electrical stimulation (ES) has emerged as a promising approach for restoring neuronal circuitry. ES facilitates neurite elongation and reprogramming through Ca2⁺-dependent pathways, while conductive nanostructures such as gold nanoparticles and MXene enhance electroporation and cellular communication. Here, inspired by the roles of miRNA regulation and EMF-mediated stimulation, we introduce a conductive granular scaffold (cGRAS) capable of in situ magnetoelectric generation of miRNA sponges targeting miR-6236. Under alternating magnetic field (AMF) irradiation, cGRAS induces wireless electrical stimulation to restore brain function, reduce neuroinflammation, and promote neuronal regeneration following TBI. This multifunctional platform represents a novel therapeutic avenue for personalized neuroregenerative medicine.[4]

Methods. Synthesis of polyethylenimine-MXene (PEI-MX) Negatively activated functional groups on MXene can induce electrostatic attraction and hydrogen bonding with positively charged PEI (Linear, MW 25 kDa, Thermo Fisher, Cat. No. 9002-98-6), characterized by its abundant repeated amino groups. First, prepare a series of dilutions from the pre-prepared PEI stock solution (10 mg mL-1) to achieve a concentration of 1 μg mL-1. Next step, centrifuge the MXene solution at a concentration of 200 μg mL-1, discard the supernatant, and subsequently add the 1.0 μg mL-1 PEI solution. Ensure thorough mixing using a sonicator to achieve homogeneity. Finally, centrifuge the mixture once again and wash it with water two to three times to remove any residual components. The combination of PEI and MXene forms a dense polymer hydrogen-bonding network that enhances mechanical strength and stability. Additionally, it expands interlayers, thereby improving ion transport speed.

Results and Discussion. The fabrication of conductive granular scaffold (cGRAS). The conductive granular scaffold (cGRAS) was fabricated by coating electromagnetic PEI–MXene (PEI-MX) loaded with miRNA sponge onto gelatin microbeads. MXene (MX) was synthesized via an etchant intercalation–stripping process, removing the A layer from the MAX precursor to yield multilayer MX (Figure 1a). Positively charged polyethylenimine (PEI) was then conjugated to negatively charged MX through electrostatic and hydrogen bonding (Figure 1b). Linear PEI (25 kDa) was selected for its reduced cytotoxicity and effective non-viral gene delivery capability. SEM and TEM images confirmed nanosheet morphology (~2.5 nm thick) and polymer shell formation (Figures 1c–d), while EDS verified successful nitrogen doping and A-layer removal (Figure 1e). XRD showed increased interlayer spacing due to PEI intercalation (Figure 1f). HRXPS analysis identified N–Ti and C–N bonds, confirming successful PEI conjugation (Figures 1g–h). Despite mild surface dissolution after 14 days, PEI-MX maintained conductivity, supported by its stable MXene network and polymeric coating.

Conclusion. In summary, electronic signaling and microRNA (miRNA) regulation critically influence neuronal fate and brain repair, yet clinical translation is limited by the lack of precise, non-viral, spatiotemporal control. Here, we present a conductive granular scaffold (cGRAS) that functions as both an antenna and a gene delivery platform for targeted miRNA modulation in traumatic brain injury (TBI). Under alternating magnetic field (AMF) stimulation, cGRAS generates wireless electrical cues to enhance electroporation and mechanotransduction, reducing inflammation and glial scarring while suppressing miR-6263 expression. This integrated strategy promotes angiogenesis, neuronal infiltration, and functional recovery, offering a promising avenue for neuroregenerative therapy.