Aptamer‐Directed Porous DNA Nanocomposite Hydrogel for Active Pulp Preservation: Immunomodulation, Stem Cell Recruitment and Reparative Dentinogenesis

ABSTRACT 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.