Bacteria-mimetic bioadhesives with multivalent mucoadhesion and drug-compatible delivery

The ability to adhere to mucus-lined tissues underpins a range of biomedical devices and therapies. However, many existing strategies rely on covalent bonding chemistries and can be unstable, cytotoxic, or incompatible with therapeutics. Here, we present a bacteria-mimetic bioadhesion strategy inspired by Vibrio cholerae. A short Bap1-derived adhesion peptide is grafted onto chitosan to strengthen mucus interactions through multivalent, cooperative secondary bonding, while preserving pH-triggered interfacial bridging behavior. Bacterial peptide grafting significantly increases adhesion energy on porcine intestine, and when paired with a tough hydrogel matrix achieves adhesion energies >400 J m^-2 without forming covalent bonds to tissue. Confocal imaging reveals deep tissue penetration (∼80 µm) with markedly enhanced mucin binding and no loss of cytocompatibility. Ex vivo intestinal delivery and in vitro drug release tests demonstrate improved drug transport and tissue exposure compared to carbodiimide-mediated covalent bonding strategy. These findings establish a bacteria-mimetic bioadhesion strategy for tissue repair and drug delivery.