ROS‐Scavenging Hydrogel Microneedles Reverse Intervertebral Disc Degeneration via Combined Mild Photothermal and NO Gas Therapy

Abstract Intervertebral disc degeneration (IVDD) is a major cause of chronic pain, and annulus fibrosus damage accelerates its progression while remaining challenging to repair due to persistent oxidative stress, chronic inflammation, and extracellular matrix (ECM) disorganization within the dense, avascular tissue. Here, a multi‑signal microenvironment‑reprogramming strategy is presented for annulus fibrosus regeneration by developing polyvinyl alcohol‑TSPBA‑polyaniline‑S‐nitrosoglutathione (GSNO) hydrogel microneedles (PTP‑G HMNs) that integrate reactive oxygen species scavenging, mild photothermal therapy (MPTT), and thermally controlled nitric oxide (NO) release, thereby overcoming the limitations of conventional NO‑releasing hydrogels or nanoparticles therapies, including short release duration, poor retention within dense fibrous tissue, and the absence of coordinated modulation of pathological signals. This platform achieves on‑demand NO delivery via the thermo‑responsive properties of GSNO while leveraging MPTT to induce heat shock protein expression, thereby synergistically suppressing inflammation, mitigating oxidative stress, promoting ECM remodeling, inhibiting apoptosis, and enhancing cell migration. In rat models, PTP‑G HMNs significantly improved disc biomechanics, preserved disc structure, and restored ECM homeostasis. By dynamically modulating pathological signals instead of passively delivering single agents, this approach offers a new therapeutic framework for IVDD with broad translational potential for other avascular fibrous tissue disorders.