Bioinspired design of peptide-based antibacterial adhesive hydrogels to prevent implant-related infections

Infection of medical implants is a serious ongoing problem worldwide, caused by bacterial adhesion and subsequent biofilm formation on the implant interface. To prevent such infection, we designed a set of catechol-functionalized cationic peptide antibacterial hydrogels that were inspired by the lysine- and DOPA-rich mussel foot protein-5. These advanced supramolecular gels are designed to coat implants providing a barrier to surface colonization and can also be injected during surgery directly to the tissue implantation site to inhibit surgical site infection. Furthermore, utilizing the gels lysine rich amino acid composition and the redox-activity of catecholic residues, these gels kill bacteria by two distinctive mechanisms: via a direct contact mechanism between the polycationic gel and the bacterial cell surface and by DOPA-mediated production of hydrogen peroxide (H₂O₂), a known antibacterial agent. We demonstrated that these gels exhibit high bactericidal activity against clinically isolated gram-positive bacteria, including the notorious multidrug resistant bacteria, MRSA. We further showed how amino acid composition and peptide sequence can modify the amount of generated H₂O₂, and consequently alter the antibacterial activity of the gel. Moreover, we characterized the ability of the gels to act as adhesives at the implant-tissue interface by utilizing lap-shear tensile strain tests.

Collectively, these results indicate that DOPA-containing hydrogels hold promise as antibacterial adhesives, suitable for implantation at the tissue-implant interface.