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Percutaneous device-related infection has greatly shortened the service period of devices and seriously reduced the quality of life of patients. Bacteria are one of the main pathogenic factors and cannot be effectively and conveniently eradicated by traditional strategies (e.g., construct coatings and introduce antibiotics), due to the complex interface among medical devices, surrounding tissue, and colonizing bacteria. Inspired by the periodontium, a universal bacteria-defensive hydrogel adapting to the complicated interface is fabricated by introducing phenol-amine chemistry to a polymeric matrix of N-hydroxyethyl acrylamide (HPC hydrogels). The HPC hydrogels with excellent toughness (2.1 MJ/m3), adhesion (10.2 and 13.2 kPa for pigskin and Ti-6Al-4V alloy, respectively), and antibacterial property (up to 99.9% for both Escherichia coli and Staphylococcus aureus) contributed to the innate microbe barrier via sealing the tissue–device interface and adaptive defense to eradicate bacteria. Meanwhile, bacterial invasion experiments demonstrate HPC hydrogels possess both a bacteria-defensive property (up to 24 h) and cell-protecting function at the same time. Furthermore, the biocompatibility of HPC hydrogels is verified in tests for in vitro cytotoxicity and in vivo irritation. Hence, the designed HPC hydrogels are considered as an emerging and universal candidate for preventing bacterial infection and can protect the deep tissue around a percutaneous device.

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