Authors
Lu Tan, Yan Zheng, Yue Lan, Zhuo Cheng, Siya Wang, Changqing Li, Yanqiu Wang, Minghan Liu
Published in
Advanced science (Weinheim, Baden-Wurttemberg, Germany). Pages e77829. Sep 27, 2026. Epub Sep 27, 2026.
Abstract
Annulus fibrosus (AF) rupture is a key structural event in intervertebral disc degeneration, but effective repair is hindered by the acidic, hypoxic and oxidative microenvironment of the avascular disc. Single-cell transcriptomic reanalysis and clinical AF specimens identified ferroptosis-associated redox imbalance as a prominent feature of advanced degeneration. Here, we developed an acid-responsive nanobot-integrated core-shell microneedle system for staged annulus fibrosus repair. The shell layer released TA@MgO2 metal-phenolic nanobots that consumed pathological H+, generated O2, and provided NIR-amplified redox buffering, thereby normalizing the early degenerative microenvironment. The core layer enabled sustained quercetin release to reinforce anti-ferroptotic and matrix-preserving effects. Mechanistically, TMH/QG+NIR suppressed ferroptosis in AF cells by epigenetically silencing ATF3 through DNMT3A-dependent promoter methylation, thereby relieving ATF3-mediated repression of SLC7A11 and restoring GPX4-dependent antioxidant defense. In a puncture-induced degeneration model, this system alleviated ferroptotic injury, improved AF integrity, preserved disc height and enhanced biomechanical resilience. These findings identify the DNMT3A-ATF3-SLC7A11 axis as a therapeutically tractable ferroptosis-regulatory pathway and establish a staged microenvironment-reprogramming strategy for AF repair.
PMID:
42801678
Bibliographic data and abstract were imported from PubMed on 28 Sep 2026.
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