Neural stem cells (NSCs) have tremendous potential to form new neural networks. However, after spinal cord injury, mitochondrial dysfunction leads to excessive accumulation of reactive oxygen species (ROS), severely impairing the neural differentiation of endogenous NSCs and thereby hindering neural regeneration. This article reports a multifunctional hydrogel, Poly(LA-Cho)/SS31 (PLCS), which is synthesized in one step through lauric acid (LA), choline small carbonate, and elamipretide (SS31).PLCS hydrogel possesses injectability, self-healing ability, tissue adhesiveness, and sequential drug release. Initially, SS31 is preferentially released to clear mitochondrial ROS and alleviate mitochondrial dysfunction. Subsequently, it is necessary to continuously scavenge ROS. Notably, PLCS hydrogel not only promotes the differentiation of neural cells into cholinergic neurons, but also increases acetyl-CoA levels and provides choline, supplying the necessary substrates for newly formed cholinergic neurons to synthesize acetylcholine and supporting their functional maturation.PLCS hydrogels achieved robust nerve regeneration and significantly improved motor, sensory, and bladder functions in a rat spinal cord injury model. RNA sequencing indicated that the PI3K-Akt pathway may contribute to spinal cord repair. This one-step synthesis method, without catalysts or organic solvents, effectively integrates the physical and biological functions of the hydrogel through simple mixing and offers a highly promising strategy for the clinical translation of spinal cord injuries and other central nervous system injuries.

Original link

Bioactive Materials ( IF 20.3 )

Pub Date : 2026-01-02

DOI: 10.1016/j.bioactmat.2025.12.009

Yiqian Luo,  Pan Jiang,  Daoqiang Huang,  Hong Li,  Jiale He,  Ruoqi Shen,  Yunheng Jiang,  Limin Rong,  Bin Liu