Aptamer-Directed Porous DNA Nanocomposite Hydrogel for Active Pulp Preservation: Immunomodulation, Stem Cell...

Vital pulp therapy (VPT) is a conservative alternative to root canal treatment that preserves the vitality of the pulp-dentin complex, yet its clinical outcomes remain inconsistent due to persistent inflammation and insufficient endogenous stem cell participation. Here, we report an injectable, aptamer-functionalized porous double-network hydrogel (DGDL-Apt) for active pulp preservation through coordinated immune-redox microenvironment reprogramming and targeted stem cell recruitment. Fabricated via an air-in-water emulsion strategy, the hydrogel integrates a dopamine-modified gelatin methacryloyl network with a supramolecular DNA-Laponite assembly, forming a mechanically robust and interconnected porous structure. Dopamine-derived catechol motifs restore redox homeostasis and attenuate inflammation, promoting macrophage polarization toward a reparative M2 phenotype. Meanwhile, sustained release of Laponite-derived ions enhances odontogenic differentiation, and CD29-targeting aptamers enable precise in situ recruitment of endogenous dental pulp stem cells. The DGDL-Apt hydrogel suppresses oxidative stress, reprograms macrophage phenotype, and promotes odontogenic differentiation in vitro. In a pulpitis rat model, it achieves rapid inflammation resolution, efficient stem cell enrichment, and formation of a continuous reparative dentin bridge. This work advances VPT from passive pulp-capping toward an active regenerative strategy and provides a general design principle for microenvironment-driven tissue preservation.