Versatile Polypeptide-Anchored Antifouling Dip-Coatings for Common Medical Implant Materials

Implant-associated infections represent a critical global healthcare challenge, exacerbated by recalcitrant biofilm formation and rising antimicrobial resistance. While antifouling polymer coatings could deter bacterial adhesion, common grafting methods such as surface-initiated polymerization face scalability and regulatory challenges. Dip-coating of antifouling polymers, facilitated by catechol-mediated anchorage to common medical implants, serves as a translationally appealing alternative. Although 3,4-dihydroxyphenylalanine (DOPA)-lysine-based oligopeptides were shown to exhibit mussel adhesive-like properties, they are not suitable for tethering high-molecular-weight (MW) antifouling polymers required for achieving adequate surface coverage. To facilitate unbiased screening for robust higher MW surface anchors, we synthesized a library of azide-terminated polypeptides─composed of DOPA alone or copolymerized with lysine, glutamate, or both randomly or in blocks in varying ratios─using N-carboxyanhydride ring-opening polymerization, achieving narrow polydispersity and excellent compositional control. These polypeptides were dip-coated onto Ti6Al4V and poly(ether ether ketone) substrates and conjugated with high-MW zwitterionic poly(sulfobetaine methacrylate) (pSBMA) by strain-promoted azide-alkyne cycloaddition. Using surface hydrophilicity as a readout of dip-coating efficiency and validated by X-ray photoelectron spectroscopy, we identified DOPA homopolymers as the optimal surface anchor for both substrates, significantly outperforming all copolymers containing lysine, glutamate, or both. The resulting pSBMA coatings resisted nonspecific protein adsorption or bacterial colonization and remained stable over one month in aqueous buffer at physiological pH and temperature. This DOPA homopolypeptide-mediated dip-coating strategy was also successfully extended to other implant substrates such as polyethylene terephthalate and silicone, establishing it as a potential universal implant surface modification approach.