Structure‐Function Co‐Assembled Polyphenol‐Diamine Network for Stable, Immunoregulatory, and Contact‐Active Healing of Oral Mucosal Defects

ABSTRACT The dynamic and microbially rich environment of the oral cavity poses unique challenges for mucosal repair, where conventional dressings fail to achieve long‐term stability, antimicrobial protection, and immune balance simultaneously. Here, we propose a structure‐function co‐assembled polyphenol‐diamine network that integrates structural robustness and biological functionality into a single interfacial system. Through the covalent co‐assembly of tannic acid and polyhexamethylene guanidine (PHMG), the network forms a release‐free antibacterial interface in which guanidinium groups remain covalently anchored yet maintain contact‐active bactericidal capability, achieving a long‐term of killing efficacy (over 96%) against S. aureus and E. coli without side effects. Concurrently, the polymerized polyphenol framework provides strong tissue adhesion via covalent anchoring and hydrogen bonding, while exerting antioxidant and immunoregulatory effects that guide macrophage polarization toward a pro‐healing M2 phenotype and promote angiogenesis through the PI3K/Akt/HO‐1 and PI3K/Akt/HIF‐1α/VEGF signaling axes. These co‐assembled biointerfaces achieve long‐term antibacterial stability, immune microenvironment reconstruction, and accelerated tissue repair under dynamic physiological conditions. The presented polyphenol‐diamine co‐assembly strategy provides a versatile and translatable strategy for engineering multifunctional, release‐free, and immunomodulatory biointerfaces across diverse tissue repair scenarios.