4D-printed smart hydrogels in oral medicine: Current applications and future perspectives

To systematically review 4D-printed hydrogels printing platforms, stimuli-responsive modalities, and applications across oral medicine subspecialties, and to identify key translational solutions for progression from laboratory research to clinical implementation.

Following PRISMA guidelines, PubMed, Web of Science, and Google Scholar were searched. To avoid omitting studies that used 3D terminology yet demonstrated time- or stimulus-responsive hydrogel behavior, core search terms included "4D printing," "stimuli-responsive hydrogel," and "3D printing of smart materials." Data extraction covered printing platforms, material compositions, stimulus types, experimental models, outcomes, and translational considerations, findings were synthesized narratively.

4D-printed hydrogels demonstrate compatibility with intraoral conditions and exhibit three principal capabilities: programmable deformation/shape memory enabling conformal fitting and force modulation; spatiotemporal, on-demand delivery of growth factors and antimicrobial agents; and tunable mechanics with self-healing to improve interfacial matching and damage tolerance. In preclinical models, improvements were observed in cell adhesion and migration, vascularization and mineralization, antimicrobial performance, and early osseointegration. Key limitations include inconsistent reporting of performance metrics, insufficient documentation of manufacturing and quality-control parameters, scarcity of clinically relevant large-animal models, and lack of consensus on clinical endpoints and regulatory classification.

4D-printed hydrogels are promising candidates for personalized oral therapies but require a harmonized design-validation-regulation pathway. Priorities include establishing multifactor validation matrices and durability endpoints under simulated intraoral temperature-pH-load conditions; engineering a responsiveness-strength balance via reversible crosslinking and nanoreinforcement; using digital twins to guide structural and parameter design; instituting stringent process control and nondestructive quality assessment; and advancing from large-animal studies to early feasibility trials anchored by clinically meaningful endpoints. Parallel progress across these fronts could accelerate translation from laboratory research to clinical practice.