Authors
Jiaying Lin, Shifeng Ling, Xiaoxiao Li, Peipei Liu, Tianqi Wu, Wankun Chen, Xiaotian Zhou, Xuemei Peng, Jionghao Yu, Juan Wang, Zhengzhe Huang, Yawei Du, Qichao Wu, Changhong Miao
Published in
Bioactive materials. Volume 69. Pages 238-257. Epub Oct 09, 2026.
Abstract
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.
PMID:
42894734
Bibliographic data and abstract were imported from PubMed on 19 Oct 2026.
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