Microneedle-mediated intelligent combination delivery for hair regeneration: A comprehensive review of technologies, mechanistic evidence, and translational prospects.

Androgenetic alopecia (AGA) is a prevalent hair-loss disorder with substantial psychosocial burden, while current treatments such as topical minoxidil and oral finasteride remain limited by insufficient follicular delivery, long-term adherence requirements, local irritation, systemic adverse effects, and recurrence after discontinuation. Microneedle (MN) technology offers a minimally invasive local intervention strategy by bypassing the stratum corneum, enhancing follicular exposure, reducing unnecessary systemic distribution, and providing mechanical stimulation to the scalp microenvironment. This review summarizes recent advances in MN-mediated intelligent combination delivery for hair regeneration, covering MN types, material selection, structural design, controlled-release strategies, and major therapeutic mechanisms, including antioxidative remodeling, pro-angiogenic support, growth factor and collagen delivery, immunomodulation, extracellular vesicle-based therapy, nanomedicine integration, and anti-androgenic intervention. We further discuss stimulus-responsive MN systems, including ROS-, pH-, enzyme-, temperature-, light-, ultrasound-, magnetic-, and electrically responsive platforms, as well as emerging closed-loop concepts that integrate sensing, data processing, and adaptive actuation. Importantly, we critically examine the gap between preclinical proof-of-concept studies and clinical translation, highlighting key challenges related to scalp-specific insertion, hair obstruction, payload stability, immune compatibility, scalable manufacturing, sterilization, patient usability, long-term safety, and regulatory uncertainty. By integrating mechanistic evidence with translational considerations, this review provides a structured perspective for researchers developing disease-tailored, microenvironment-oriented, and clinically feasible MN-based strategies for hair regeneration.