Bioinspired Stratified Janus Hydrogel Enables Neuro‐Osteogenic Regeneration via Microenvironment‐Matched Repair After Tooth Extraction

Abstract Deeply impacted third molar extractions often cause alveolar sockets with nerve injury, where persistent inflammation impairs bone and peripheral nerve regeneration. However, the mechanical rigidity required for osteogenesis conflicts with the soft, conductive environment for neurogenesis, challenging for integrated repair. To address this, a Janus hydrogel (CD/CDP) has a stiff chitosan‐methacrylate (CSMA)‐based (C) upper layer and a soft, electroconductive polypyrrole‐polydopamine nanoparticles (PPy‐PDA NPs) (P) doped lower layer, loaded with diclofenac sodium (D) for immunomodulation. This stratified design delivers compartmentalized mechanical and electrical cues while reprogramming inflammation via M2 macrophage polarization. In vitro, the CD layer promoted bone marrow mesenchymal stem cell (BMSC) osteogenesis through mechanotransduction, while the CDP layer facilitated Schwann cell proliferation and process extension via phosphoinositide 3‐kinase/protein kinase B (PI3K/AKT) signaling. In vivo, the hydrogel increased woven bone formation by 2.40‐fold over the inferior alveolar nerve injury (IANI) group and 1.22‐fold over gelatin sponge (GS). Peripheral myelin regeneration improved by 1.76‐fold and 1.13‐fold. These effects occurred in parallel accompanied by reduced tumor necrosis factor‐α (TNF‐α) and interleukin (IL‐6). This microenvironment‐guided janus hydrogel offers a spatially resolved strategy for dual‐tissue regeneration and holds translational promise for challenging oral defects involving bone and peripheral nerve injury.