Titanium dioxide in oral medicine: advancements in drug delivery and tissue engineering for targeted therapies

Abstract

Titanium dioxide (TiO₂) has transitioned from an inert implant coating to an active nanoplatform for localized drug delivery and tissue engineering in oral medicine. Its high surface area, tunable porosity, and favorable biocompatibility enable site‑specific, sustained therapeutic delivery in the challenging environment of the oral cavity. This review addresses a key gap in the literature by providing a focused, clinically oriented synthesis of TiO₂‑based systems specifically for periodontics, oral oncology, and implantology, rather than a broad survey of general biomedical or non‑oral applications. Particular emphasis is placed on recent studies from the last decade that link TiO₂ nanostructural design parameters—such as nanotube geometry, surface functionalization, and noble‑metal or transition‑metal doping—to quantitative outcomes in drug‑release kinetics, antimicrobial efficacy, and hard and soft tissue regeneration at oral sites. TiO₂ nanostructures are discussed as multifunctional platforms that can encapsulate antibiotics, anti‑inflammatory agents, and anticancer drugs, provide pH‑ or light‑responsive release, enhance gingival and bone cell adhesion, and exert photocatalytic antimicrobial and photodynamic effects against peri‑implant and tumor‑associated biofilms. In tissue engineering, nano‑engineered TiO₂ coatings and composite scaffolds are evaluated for their ability to promote osseointegration, stabilize peri‑implant soft tissues, and support the reconstruction of periodontal and maxillofacial defects. The review also critically appraises the translational landscape by outlining long‑term safety concerns (including chronic exposure and inflammasome activation), variability in synthesis and functionalization protocols, and current regulatory and manufacturing barriers that limit routine clinical adoption. Future directions highlight the development of multi‑stimuli‑responsive TiO₂ systems, sustainable green synthesis routes, and integration with advanced regenerative strategies such as stem cell‑based therapies and patient‑specific, additively manufactured scaffolds to more effectively bridge preclinical promise and clinical implementation in oral medicine. Not applicable.