Significant Suppression of Staphylococcus aureus Colonization on Intramedullary Ti6Al4V Implants Surface-Grafted with Vancomycin-Bearing Polymer Brushes.

Abstract

Orthopedic implant-associated bacterial infection presents a major health threat due to tendency for periprosthetic bacterial colonization/biofilm formation that protects bacteria from host immune response and conventional antibiotic treatment. Using surface-initiated atom transfer radical polymerization and copper-catalyzed azide-alkyne cycloaddition (CuAAC), alkynylated vancomycin is conjugated to azido-functionalized side chains of polymethacrylates grafted from Ti6Al4V. High-efficiency CuAAC across the substrate is confirmed by complete surface conversion of azides by X-ray photoelectron spectroscopy (XPS) and elemental mapping of changing characteristic elements. The vancomycin-modified surface (Ti-pVAN) significantly reduces in vitro adhesion and colonization of Staphylococcus aureus (S. aureus), a main bacterial pathogen responsible for periprosthetic infection and osteomyelitis, compared to untreated Ti6Al4V, supporting retained antibacterial properties of the covalently conjugated antibiotics. When the surface-modified intramedullary Ti-pVAN pins are inserted into mouse femoral canals infected by bioluminescent Xen29 S. aureus, significantly reduced local bioluminescence along with mitigated blood markers for infection are detected compared to untreated Ti6Al4V pins over 21 days. Ti-pVAN pins retrieved after 21 days are confirmed with ∼20-fold reduction in adherent bacteria counts compared to untreated control, supporting the ability of surface-conjugated vancomycin in inhibiting periprosthetic S. aureus adhesion and colonization.