Significant Suppression of S. 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 bacteria colonization/biofilm formation which protects bacteria from host immune response and conventional antibiotic treatment. Using surface-initiated atom transfer radical polymerization (SI-ATRP) 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 Xen-29 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.