Dual-mode light/ROS-responsive microneedles enable adaptive nitric oxide therapy across tissue depths.

Developing therapeutic biomaterials capable of adapting their activation mechanisms according to tissue accessibility remains a major challenge for treating heterogeneous pathological microenvironments. Herein, we report a microenvironment-adaptive hydrogel microneedle platform (CD/MN) by integrating L-arginine-derived carbon dots into a ROS-responsive hydrogel matrix, enabling tissue-depth-dependent nitric oxide (NO) therapy through complementary activation pathways. Under external light irradiation, photo-generated singlet oxygen facilitates NO generation for rapid antibacterial therapy in superficial infected wounds. In contrast, in deep tissues where light penetration is inaccessible, endogenous pathological ROS activates hydrogel degradation, enabling sustained release of L-arg CDs and prolonged NO-mediated immunoregulatory bioactivity. The microneedle architecture further provides localized delivery and prolonged tissue retention, thereby enhancing therapeutic efficiency. Importantly, the same material platform operates through light-triggered activation in superficial infected burns and ROS-driven autonomous activation in intervertebral disc degeneration, demonstrating adaptive therapeutic behavior across tissues with distinct activation accessibility. In vitro studies reveal a ROS-initiated, NO-dominated antibacterial mechanism, while in vivo studies demonstrate effective bacterial clearance, inflammation resolution, angiogenesis, extracellular matrix remodeling, and attenuation of intervertebral disc degeneration. Collectively, this work establishes a tissue-adaptive microneedle platform capable of switching activation modes according to tissue accessibility, providing a generalizable design strategy for intelligent biomaterials targeting heterogeneous ROS-associated diseases.