Rationally Designed Microneedles that Remodel the Follicular Microenvironment for Androgenetic Alopecia Therapy

Vollständiger Abstract

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Abstract Androgenetic alopecia (AGA) is a systems-level disorder driven by converging metabolic, signaling, oxidative, vascular, and inflammatory alterations within hair follicles and their niches. Current single-target therapies exhibit limited efficacy due to poor penetration across the scalp’s dual barriers. Although chemical and physical enhancers have been explored, they lack the spatiotemporal precision required for multidimensional intervention. Microneedles (MNs) have evolved beyond physical penetrators into intelligent, programmable therapeutic platforms. However, a comprehensive framework tracing their progression from permeation enhancers to multifunctional modulatory devices is currently unavailable. This review addresses this gap by examining follicle physiology, AGA pathology, and engineering principles that enable MNs to overcome scalp barriers. It systematically charts the evolution of MNs into smart, multitarget delivery systems, emphasizing the value of traditional Chinese medicine-inspired strategies for holistic follicular remodeling by targeting the multidimensional pathogenesis of AGA. Furthermore, it critically evaluates recent patents, clinical trials, and translational challenges. By providing a roadmap for designing next-generation MN therapies, this review bridges knowledge gaps and redefines AGA therapeutic paradigms, signaling a shift from isolated target inhibition toward systems-level regulation of follicular ecosystems.