Hierarchical Titania Nanotube-Graphene Oxide-Arginine Interfaces for Tunable Drug Release and Enhanced Antibiofilm Performance.

Abstract

Implant-associated infections (IAIs) driven by multidrug-resistant pathogens, such as Methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus epidermidis (S. epidermidis), are two of the most challenging organisms responsible for recurrent implant failures. To mitigate this problem, we have developed broad-spectrum, efficient antibiofilm coatings for the titanium implant surface, which is modified with titania nanotube arrays (TNTA) via electrochemical methods. The resulting TNTA loaded with vancomycin (V-TNTA) and coated with polycaprolactone (PCL) fibers incorporating functionalized graphene oxide (GO) and l-arginine (VPGOA-TNTA) to restrict biofilm formation during the early four-week post-implantation. Spectroscopic and microscopic characterization techniques were performed to confirm the loading of vancomycin and successful coating of GO and l-arginine, including high-resolution scanning electron microscopy (HR-SEM) with energy-dispersive X-ray spectroscopy (EDS), transmission electron microscopy (TEM), X-ray diffraction (XRD), attenuated total reflectance and Fourier transform infrared (ATR-FTIR) spectroscopy, and wettability analyses. Next, in vitro antibacterial investigations revealed significant antibacterial and antibiofilm efficacy of VPGOA-TNTA-modified surfaces against MRSA and S. epidermidis, as evidenced by growth curves, CFU/mL, and relative biofilm reduction on the implant surface. Reactive oxygen species (ROS) analysis confirmed the enhanced antibacterial activity of VPGOA-TNTA. Further, the VPGOA-TNTA demonstrated significant cell viability with MG63 cells. Notably, VPGOA-TNTA-modified surfaces also exhibited excellent hemocompatibility. Furthermore, a scratch assay with 3T3 fibroblasts demonstrated remarkable wound-healing activity. In addition, the Alzarin Red S (ARS) staining assay confirmed osteoblastic mineralization on VPGOA-TNTA, showing substantial calcium deposition in MG63 cells. Overall, our findings indicate that VPGOA-TNTA is a promising orthopedic implant material for eradicating the MRSA and S. epidermidis infections while promoting osseointegration.