Environment-adaptive microneedle design strategies for precision oral disease treatment: From material innovation to clinical translation.

Oral diseases affect over 3.6 billion people worldwide and remain therapeutically challenging due to the oral cavity's dynamic physiological environment, including constant moisture, complex microbiota, and mechanical stress. Conventional drug delivery approaches are often limited by poor retention, low bioavailability, and inadequate targeting. Microneedle (MN) systems, offering minimally invasive and localized delivery, represent a promising alternative. This review proposes a comprehensive framework for the design of oral-environment-adaptive microneedles (MNs), focusing on three core dimensions: rational structural design, material innovation, and drug functionalization. We classify five major MN types, including solid, coated, hollow, dissolvable, and hydrogel, and systematically evaluate their respective mechanisms and suitability for oral applications. We then analyze key delivery barriers such as epithelial thickness, intercellular biochemical defenses, and immune-microbial dysbiosis. Design solutions include swelling-tip and interlocking structures for enhanced retention, catechol-functionalized mucoadhesive polymers for wet adhesion, and dual-crosslinked hydrogels for dynamic responsiveness. Functional enhancements such as antimicrobial agents and macrophage-polarizing immunomodulators further broaden therapeutic utility. Clinical studies have confirmed the safety and efficacy of MNs in applications such as anesthesia, mucosal healing, and periodontal regeneration. Together, these insights provide a roadmap for the rational design and clinical translation of personalized MN therapies for oral diseases.