Nano bio-responsive systems avoiding methicillin resistant Staphylococcus aureus colonization on an implant surface

• We nanoengineered implants to help host cells outcompete S. aureus for the surface. • Bio-adhesive surfaces functionalized with polymer brushes acted as mammalian cell recruiter. • A polyphosphate-coated chimeric endolysin nanolayer impaired Staphylococcus aureus. • Biointerface efficacy was validated using S. aureus and MC3T3 preosteoblast-like cell. Biomaterial-associated infections caused by Staphylococcus aureus represent a race between bacterial colonization and mammalian cell integration on implant surfaces. If bacteria win, biofilm forms, often causing persistent infection. To favor host cells, we developed a nano bio-responsive system (NanoBioRS) with two synergistic defense lines. The first is a bio-adhesive surface with polymer brushes that recruit mammalian cells. The second is a nano-bioactive coating of polyphosphate-encapsulated chimeric phage endolysin nanoparticles (M23-PP), activated by alkaline phosphatase—an enzyme vital for bone development and biofilm life cycle. Using metal-free surface-initiated atom transfer radical polymerization, we synthesized poly(polyethylene glycol methacrylate) (PPEGMA), poly(glycidyl methacrylate) (PGMA), and their block copolymer polymer brushes. These brushes were characterized via ellipsometry, FTIR, contact angle, and XPS. Functionalization with Arg-Gly-Asp (RGD) peptide enhanced MC3T3-E1 preosteoblast recruitment, as confirmed by fluorescence microscopy. Further bioactivation with M23-PP nanoparticles provided targeted antibacterial action. NanoBioRS was biocompatible and its efficacy was validated through competitive colonization assays with methicillin sensitive or resistant S. aureus , together with MC3T3-E1 cells. This biocompatible platform shows strong potential to prevent bacterial colonization of implants.