Applications of immunomodulatory nanoparticles in dentistry

Oral inflammatory diseases such as periodontitis, peri-implantitis, and oral mucositis contribute significantly to tooth loss, impaired oral function, and systemic comorbidities. These conditions are driven by dysregulated immune responses, leading to persistent inflammation and poor tissue regeneration. Conventional treatments mainly target microbial reduction but overlook immune imbalance, limiting long-term efficacy. Immunomodulation offers a promising strategy to restore homeostasis and promote repair. Nanoparticles present a versatile platform for immunotherapy owing to their tunable size, surface chemistry, and capacity to target immune cells or respond to pathological cues. This review (PubMed, Scopus, Web of Science, 2015-2025) explores immunomodulatory nanoparticles in dentistry, grouped as organic (lipid-based, polymeric, self-assembled), inorganic (metallic, metal oxide, ceramic), exosome- and extracellular vesicle-derived, and hybrid systems. These platforms modulate macrophage polarization, cytokine production, and T cell balance to control inflammation and support regeneration. Advanced biomimetic designs further integrate antimicrobial, antioxidative, and pro-regenerative features. Despite encouraging preclinical data, translation faces challenges, including limited understanding of immune-nanoparticle interactions, safety issues, regulatory hurdles, lack of predictive models, and absence of standardized characterization protocols. Future directions include smart, personalized, and biomimetic systems, improved in vivo models, companion diagnostics, and harmonized evaluation standards, positioning these nanotechnologies as transformative tools in precision dental medicine.