Wet-adhesive metabolic hydrogel for osteoimmune-guided extraction socket healing

Dynamic wet interfaces, exemplified by tooth extraction sockets, demand dressings that can maintain firm adhesion despite constant salivary flushing, suction, and mastication while actively guiding tissue regeneration. Conventional hemostatic materials detach easily under these forces, destabilizing clots and impairing healing. Here, we develop a photocurable wet-adhesive metabolic hydrogel (WAM-Gel) that integrates interfacial stability with bioinstructive metabolic signaling. The hydrogel is formed from <i>N</i>-acryloyl glycinamide (NAGA) and acryloyl-6-aminocaproic acid <i>N</i>-hydroxysuccinimide ester (AANHS), which in situ photo-crosslink into a hydrogen-bond-rich, covalently anchored dual network. This architecture provides high compressive strength, considerable burst pressure, and exceptional shear adhesion, thereby ensuring stable sealing under physiologic suction, chewing, and brushing in daily oral activities. Controlled swelling further ensures conformal socket filling and reliable clot stabilization. Beyond adhesion, the hydrogel incorporates β-hydroxybutyrate (BHB) to endow the construct with metabolic immunoregulatory functionality. As a metabolic regulator, BHB orchestrates osteoimmune programming by coupling macrophage phenotype remodeling with enhanced osteogenic differentiation, thereby fostering a pro-regenerative microenvironment. This dual action suppresses inflammatory cytokines, promotes M2 polarization, augments angiogenesis, and accelerates osteogenesis. <i>In vivo</i>, WAM-Gel enhanced early neovascularization, collagen maturation, and bone formation in rat extraction models, and preserved ridge contour with improved trabecular microarchitecture in beagle sockets compared with standard care. Together, this work supports a bioactive sealing strategy that integrates wet stable adhesion and metabolic regulation for osteoimmune guided regeneration at dynamic oral interfaces.