Wireless magnetoelectric hydrogel spray reprograms the CXCL12-autophagy axis for spatiotemporally controlled cervical nerve root regeneration.

Abstract

Cervical nerve root injury (CNRI) presents significant clinical challenges owing to complex anatomical constraints and poor intrinsic regenerative capacity. In this study, we introduce an in situ-sprayable magnetoelectric hydrogel (DG/FBD) engineered through dynamic covalent assembly and photo-triggered stabilization. The construction of critical boronate ester bonding between dopamine-modified Fe₃O₄@BaTiO₃ nanoparticles and phenylboronic acid-functionalized dextran endows DG/FBD with optimal viscosity (87 mPa s), rapid gelation (<2s) and robust tissue adhesion (22.11 kPa), allowing for precise deposition along tortuous nerve roots while conforming to branched cervical anatomy. We then establish a wireless magnetic actuation platform with conductivity modulation enabled spatiotemporally controllable bioelectronic interfacing. In CNRI models loading with magnetic stimulation, we found the hydrogel spray significantly promotes axonal regeneration and myelination, and importantly, improving functional recovery, including enhanced pain and temperature sensation, as well as increased grip strength. We also demonstrate accelerated neural differentiation of BMSCs and attenuated astrogliosis by in vitro studies. Mechanistically, we reveal that magnetoelectrically triggered CXCL12 upregulation drives Schwann cells remodeling through PI3K/AKT/mTOR inhibition and enhances autophagic flux, establishing a bioelectronic-metabolic bridge where the CXCL12-autophagy axis emerges as a fundamental regulatory node for neural regeneration. Collectively, our work pioneers wireless magnetoelectric regulation of chemokine-directed neural repair via an integrated sprayable hydrogel system that overcomes cervical interfacing constraints, establishing a promising platform for spatiotemporal microenvironmental reprogramming in complex neuropathies.