A Tightly Interlayer Bonded, Synchronously In Situ Co‐Injectable, Wet‐Adhesive, Hierarchically Biofunctionalized Bilayer Hydrogel for Functional Attachment and Orderly Periodontal Regeneration

ABSTRACT Periodontitis, the sixth most prevalent global disease, causes tooth loss and systemic disorders, imposing a significant global burden. Functional regeneration of the periodontium remains a major challenge due to the hierarchical soft‐hard tissue interface and complex spatiotemporal functional demands. In this study, a synchronously in situ co‐injectable, interlayer‐bonding, and wet‐adhesive bilayer hydrogel (Bio‐Fun bilayer) consisting of PCAC and PCMC layers is developed. An anti‐delamination interface is engineered via polymer chain topological entanglement and dynamic boronate ester and ionic networks, while precise complex viscosity matching enables synchronized microscale laminar co‐extrusion. Concurrently, the hydrogel maintains wet adhesion, especially to moist root and bone surfaces. Spatiotemporal biofunctionalization is achieved by loading microRNA‐26a liposomes in the PCAC layer to activate Wnt/β‐catenin signaling for osteogenesis, and covalently tethering a PDGF‐BB mimetic peptide within the PCMC layer to trigger PI3K/Akt‐LOX signaling for fibroblast recruitment and functional collagen formation. In vivo, the Bio‐Fun bilayer hydrogel achieves integrated regeneration of alveolar bone and aligned periodontal ligament fibers, forming Sharpey's fiber‐like structures with firm bone‐ligament attachment. Meanwhile, the modular and injectable design might provide broad reference for the reconstruction of periodontal, osteochondral, and other soft‐hard tissue interfaces.