Rapid Photo-Sonotherapy for Clinical Treatment of Bacterial Infected Bone Implants by Creating Oxygen Deficiency Using Sulfur Doping

Abstract

Periprosthetic infection is considered the main cause of implant failure, which is expected to be solved by fabricating an antibacterial coating on the surface of the implant. Nevertheless, systemic antibiotic treatment still represents the mainstream method for preventing infection, and few antibacterial coatings are applied clinically. This is because the externally introduced traditional antibacterial coatings suffer from the risk of invalidation and tissue toxicity induced by the consumption of antibacterial agents, degradation, and shedding. In this work, we proposed a rapid photo-sonotherapy by creating an oxygen deficiency on a titanium (Ti) implant through sulfur (S)-doping (Ti–S–TiO2–x ), which endowed the implants with great sonodynamic and photothermal ability. Without introducing an external antibacterial coating, it reached a high antibacterial efficiency of 99.995% against Staphylococcus aureus under 15 min near-infrared light and ultrasound treatments. Furthermore, bone infection was successfully treated after combination treatments, and improved osseointegration was observed. Importantly, the S-doped Ti implant immersed in water for 6 months showed an unchanged structure and properties, suggesting that the Ti implant with intrinsic modification showed stable antibacterial performance under exogenous stimuli with a high antibacterial performance in vivo. This photo-sonotherapy based on sulfur doping is also promising for cancer therapy with biosafety.

Recent Advances in Nanomaterial‐Assisted Combinational Sonodynamic Cancer Therapy

“…[55] Instead of given oxygen vacancies by reduction, Su et al created oxygen vacancies through sulfur (S) doping to implement enhanced SDT for antimicrobial treatment ( Figure 6D). [56] Recently, our group also proposed a strategy to enhance the SDT effect of TiO 2 by simultaneously integrating precious metal Pt nanoparticles and an oxygen-deficient layer to the surface of TiO 2 , which was demonstrated to greatly improve the separation efficiency of electrons and holes to bilaterally enhance the SDT effect ( Figure 6E). [25c] Just recently, Liu's group first developed oxygen deficient structural ultrafine titanium monoxide nanorods (TiO 1+x NRs) with a reduced bandgap than that of TiO 2 for enhanced SDT ( Figure 6F).…”

“…Reproduced with permission. [56] Copyright 2020, American Chemical Society. E) Schematic overview of the preparation of HPT-DOX nanoparticles and their anticancer properties in tumor cells.…”

“…[55] The existence of an Reproduced with permission. [56] Copyright 2020, American Chemical Society. C) Schematic of D-ZnO x :Gd for synergistic SDT-PTT tumor eradication.…”

“…fabricated a multifunctional Ti–S–TiO 2− x titanium implant with a sulfur‐doping TiO 2 layer to simultaneously implement SDT and PTT for antibacterial treatment without introducing an external antibacterial coating ( Figure A). [ 56 ] The created oxygen‐deficient TiO 2 layer endowed the titanium implants not only with enhanced SDT by effectively inhibiting the recombination of electrons and holes, but also with a robust PTT property. The efficiency of the combination treatment of Ti–S–TiO 2− x was evaluated both in vitro and in vivo.…”

NIR light-assisted phototherapies for bone-related diseases and bone tissue regeneration: A systematic review

“…However, few reviews have discussed NIR light-assisted phototherapies for bone-related diseases and bone tissue regeneration. Recent studies have reported NIR light-induced antibacterial and anti‑inflammatory therapeutic effects for the treatment of bone‑related diseases 15 - 18 . At the same time, several studies have demonstrated that NIR light triggered mild localized heat, and the photoelectronic microenvironment could accelerate bone tissue regeneration 19 , 20 .…”