Pathological Microenvironment-Inspired Design of Adaptive Microneedle Platforms for Oral Mucosal Disease Therapy: A Narrative Review

The oral mucosa presents a challenging therapeutic interface characterized by continuous hydration, mechanical disturbance, microbial complexity, and dynamically evolving pathological conditions. This narrative review examines microneedle (MN) platforms for oral mucosal disease therapy from a pathological microenvironment-inspired perspective, with emphasis on interfacial adaptation, pathological signal responsiveness, infection control, and spatiotemporal drug delivery. Current evidence indicates that oral MNs can improve local retention, transmucosal delivery, antimicrobial activity, inflammatory regulation, and tissue repair. Endogenous ROS- and enzyme-responsive systems, externally triggered platforms, and multilayer or core–shell designs have further enabled stimulus-dependent or sequential therapeutic delivery. However, most current systems remain dependent on predefined material dissolution, degradation, or external stimulation rather than true feedback-driven adaptation to changing disease states. Major gaps include the lack of clinically validated response thresholds, insufficient oral-specific disease models, inconsistent evaluation of mechanical performance and mucosal retention, limited long-term biosafety data, and unresolved manufacturing and regulatory challenges. Future development should focus on standardized oral-specific evaluation and the integration of pathological sensing with programmable therapeutic delivery to improve the clinical applicability of adaptive MN platforms.