Bioactive materialsOct 19, 2026

Injectable mRNA-made short fibers send timed mechanical and genetic signals to reshape support cell structure for nerve healing

mRNA Technology Weekly Brief ↗PubMed ↗DOI ↗

Updated Oct 20, 2026

Abstract

A greater than 4-fold increase in Schwann cell abundance and improved conduction velocity were observed at day 28 following peripheral nerve injury treatment.

Defective Schwann cell repair programs hinder recovery after peripheral nerve injury.
An injectable mRNA therapy platform reprograms Schwann cell dynamics to improve repair processes.
Early treatment induces a temporary increase in c-Jun protein, enhancing myelin debris clearance and promoting repair.
Sustained mechanical stimulation following c-Jun activation supports Schwann cell alignment and remyelination.
Both laboratory and animal studies show improved sensory and motor recovery in treated subjects compared to untreated controls.

Simplified

Defective Schwann cell (SC) repair programs mediated by cytoskeletal remodeling severely limit functional recovery following peripheral nerve injury (PNI). Here, we report an in situ mRNA therapy enabled by an injectable, mechanically/genetically time-sequenced short-fiber platform (A-CJM-LNP@SF) that reprograms SC cytoskeletal dynamics to accelerate repair. Polydopamine-coated, mechanically sheared electrospun short fibers adsorb c-Jun mRNA-loaded lipid nanoparticles (LNPs), enhancing local retention and providing sustained mechanical cues. Early after injury, efficient transfection elicits a transient intracellular c-Jun pulse that activates Rac1/Cdc42-associated cytoskeletal programs, promoting myelin debris clearance and induction of the repair phenotype. Subsequently, the relatively slow-acting mechanical stimulation, once released from c-Jun inhibition, sustains RhoA signaling, driving SC alignment and remyelination. In vitro and in vivo data confirm coordinated SC phenotypic transitions and remyelination, with >4 folds increases in day-3 SC abundance and day-28 conduction velocity over untreated crush, substantially improving sensory and motor functional recovery. Overall, coupling transient mRNA delivery with sustained mechanical stimulation offers a powerful strategy for PNI regeneration.

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Injectable mRNA-made short fibers send timed mechanical and genetic signals to reshape support cell structure for nerve healing

Abstract

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