Toward intelligent immune microneedles: Strategies for sensing, therapy, and immune regulation

The human immune system defends against pathogens, regulates inflammation, and supports tissue repair, but overactivity or dysregulation can compromise these functions. While wearable devices have been explored for immune modulation, conventional designs remain limited in detecting and delivering large immune-related biomolecules. Microneedle (MN) technology has recently emerged as a minimally invasive platform that penetrates the stratum corneum painlessly, providing direct access to dermal immune components and enabling precision intervention. Despite increasing interest, systematic reviews focusing specifically on immune-oriented microneedles are still scarce. This review comprehensively examines advances in intelligent immune microneedle systems, with a focus on strategies for sensing, therapy, and immune regulation. First, the classification, fabrication, and modification of immune microneedles are introduced. Current sensing strategies, including detection principles, interstitial fluid extraction, and monitoring of immune biomarkers, are then discussed. Next, therapeutic applications are summarized, covering drug delivery modalities, passive stimuli-responsive immune microneedles, and treatments for wounds, inflammation, and cancer. Finally, emerging intelligent microneedle systems that integrate wireless control, closed-loop feedback, and machine learning are highlighted as promising approaches for adaptive and personalized immune regulation. This review aims to provide a clear conceptual framework for researchers and clinicians, while fostering interdisciplinary collaboration toward the development of next-generation immune health solutions.