Efficacy of pH‐Responsive Surface Functionalized Titanium Screws in Treating Implant‐associated <i>S. aureus</i> Osteomyelitis with Biofilms Formation

Implant-associated Staphylococcus aureus (S. aureus) osteomyelitis (IASO) leads to high orthopedic implant failure rates due to the formation of Staphylococcal abscess community within the bone marrow and bacterial colonization in the osteocyte lacuno-canalicular network (OLCN). To address this, antimicrobial peptides (HHC36)-loaded titania nanotubes (NTs) are developed on titanium screws (Ti-NTs-P-A), which integrate pH-responsive polymethacrylic acid to control HHC36 release for eradicating bacteria in IASO. Colony-forming unit assay confirmed that Ti-NTs-P-A screws maintained sustainable antibacterial effectiveness, killing over 65% of S. aureus even after multiple bacterial solution replacements. Notably, Ti-NTs-P-A screws exhibit significant pH-responsive HHC36 release behavior and bactericidal activity, consistent with the phenotype of peptides-killed bacteria from scanning electron microscopy. Transcriptome sequencing results reveal that Ti-NTs-P-A screws interfered with ribosome formation and disrupted the arginine biosynthesis, which is crucial for bacterial survival in acidic environments. In the non-infected implant model, the bone-implant contact ratio of the Ti-NTs-P-A screw is 2.3 times that of the clinically used titanium screw. In an IASO model, Ti-NTs-P-A screws effectively eradicated bacteria within the OLCN, achieving an 80% infection control rate and desirable osteointegration. Collectively, Ti-NTs-P-A screws with pH-responsive antibacterial properties exhibit great potential for eradicating bacteria and achieving osseointegration in IASO.