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SF-based electro-responsive conductive composite NGCs promote peripheral nerve regeneration by inhibiting ferroptosis in Schwann cells.

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Title: SF-based electro-responsive conductive composite NGCs promote peripheral nerve regeneration by inhibiting ferroptosis in Schwann cells.
Authors: Han, Guanjie1,2 (AUTHOR) han.guanjie@zs-hospital.sh.cn, Fu, Tengfei1,2 (AUTHOR) fu.tengfei@zs-hospital.sh.cn, Xiang, Xingdong1,2,3 (AUTHOR) xiang.xingdong@zsgmc.sh.cn, Wei, Ping1,4 (AUTHOR) wei.ping@zs-hospital.sh.cn, Huang, Lei5 (AUTHOR) HL941026@163.com, Wang, Ning6 (AUTHOR) wangning2025@outlook.com, Bian, Mengxuan7 (AUTHOR) Dr.Bianmx@outlook.com, Lu, Shunyi8 (AUTHOR) lushunyi@suda.edu.cn, Su, Dihan6 (AUTHOR) sudihan@126.com, Wang, Jiayi1,9,10 (AUTHOR) orth_wjy@sjtu.edu.cn, Jiang, Libo1,6 (AUTHOR) jiang.libo@zs-hospital.sh.cn, Zhang, Jian1,2 (AUTHOR) zhang.jian@zs-hospital.sh.cn
Source: Chemical Engineering Journal. May2026, Vol. 535, pN.PAG-N.PAG. 1p.
Subjects: Schwann cells, Ferroptosis, Peripheral nerve injuries, Electric stimulation, Vitamin K2, Nervous system regeneration, Polypyrrole, Silk fibroin
Abstract: Peripheral nerve injury (PNI) imposes a substantial burden due to its high disability rate. Although drug-delivering nerve guidance conduits (NGCs) are widely used for PNI repair, their efficacy remains limited, largely because of inefficient, poorly controllable drug release and the hostile early microenvironment driven by oxidative stress and iron metabolism imbalance. Ferroptosis is a key manifestation of this post-injury iron dysregulation. Here, we identify Schwann cell ferroptosis as an early, temporally confined pathological process after PNI and accordingly develop an electro-responsive conductive silk fibroin/polypyrrole (SF/PPy) NGC loaded with menaquinone-4 (MK-4) for temporally targeted local anti-ferroptotic therapy. Electrical stimulation (ES) markedly enhanced MK-4 release, increasing the 14-day cumulative release from 11.20 ± 0.43% to 23.5 ± 0.84%. In vitro , under ES, MK-4 suppressed Schwann cell ferroptosis mainly via activation of ferroptosis suppressor protein 1 (FSP1). In vivo , SF/PPy/MK-4 conduits combined with ES modulated the early post-injury microenvironment, inhibited Schwann cell ferroptosis, and significantly improved sensory and motor functional recovery. Overall, this study establishes Schwann cell ferroptosis as an early therapeutic target in PNI and presents a conductive NGC platform integrating ES responsiveness with temporally targeted microenvironmental modulation to promote peripheral nerve regeneration. [Display omitted] • Schwann cell ferroptosis peaks during the early phase after peripheral nerve injury. • MK-4-loaded electro-responsive silk fibroin/polypyrrole nerve conduit designed. • Electrical stimulation enhances MK-4 release from the nerve conduit. • Temporally targeted suppression of Schwann cell ferroptosis achieved. • Combined conduit-electrostimulation therapy promotes early functional recovery. [ABSTRACT FROM AUTHOR]
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Database: Engineering Source
Description
Abstract:Peripheral nerve injury (PNI) imposes a substantial burden due to its high disability rate. Although drug-delivering nerve guidance conduits (NGCs) are widely used for PNI repair, their efficacy remains limited, largely because of inefficient, poorly controllable drug release and the hostile early microenvironment driven by oxidative stress and iron metabolism imbalance. Ferroptosis is a key manifestation of this post-injury iron dysregulation. Here, we identify Schwann cell ferroptosis as an early, temporally confined pathological process after PNI and accordingly develop an electro-responsive conductive silk fibroin/polypyrrole (SF/PPy) NGC loaded with menaquinone-4 (MK-4) for temporally targeted local anti-ferroptotic therapy. Electrical stimulation (ES) markedly enhanced MK-4 release, increasing the 14-day cumulative release from 11.20 ± 0.43% to 23.5 ± 0.84%. In vitro , under ES, MK-4 suppressed Schwann cell ferroptosis mainly via activation of ferroptosis suppressor protein 1 (FSP1). In vivo , SF/PPy/MK-4 conduits combined with ES modulated the early post-injury microenvironment, inhibited Schwann cell ferroptosis, and significantly improved sensory and motor functional recovery. Overall, this study establishes Schwann cell ferroptosis as an early therapeutic target in PNI and presents a conductive NGC platform integrating ES responsiveness with temporally targeted microenvironmental modulation to promote peripheral nerve regeneration. [Display omitted] • Schwann cell ferroptosis peaks during the early phase after peripheral nerve injury. • MK-4-loaded electro-responsive silk fibroin/polypyrrole nerve conduit designed. • Electrical stimulation enhances MK-4 release from the nerve conduit. • Temporally targeted suppression of Schwann cell ferroptosis achieved. • Combined conduit-electrostimulation therapy promotes early functional recovery. [ABSTRACT FROM AUTHOR]
ISSN:13858947
DOI:10.1016/j.cej.2026.175581