| Non-invasive therapeutic strategies for treating acute bacterial infections and cancers have attracted significant attention so far.Although the phototherapy,has been widely investigated,its Achilles' heel is its limited ability to penetrate deep into tissues.Ultrasound(US)therapy was developed to address this shortcoming as US can penetrate more than 5 cm under the skin without being affected by human skin or connective tissue.And the most representative ultrasonic strategy is sonodynamic therapy(SDT),which can produce reactive oxygen species(ROS)using sonosensitizers under the cavitation effect so far.However,the therapeutic efficiency of SDT is limited by the hypoxic microenvironment of the deep tissues of lesions.Sono-thermal therapy can be applied to address this issue.It is well known that the high-intensity focused ultrasound(HIFU)is an advanced technology using acoustic lens to focus ultrasound on a point.The focused ultrasound is able to be deposited and converting the mechanical energy to heat(65–100 °C)in 0.5–1.0 s to ablate lesions in vivo in clinical trials.However,HIFU cannot kill bacteria efficiently through high temperature in a short time.Also,organisms have good absorption of US,indicating that the high-energy US can easily lead to high temperature in biological tissue.The development of controllable sono-thermal biomaterials bacterial infection on the surface of implant in vivo has been rarely discussed in the literature so far.In summary,it is necessary and meaningful to provide a facile strategy to realize the mild,safe and controllable sono-thermal ability of materials for antibacterial treatment in the deep tissues.In this work,the Ti-red phosphorus(Ti-RP)heterojunction interface with controllable sono-thermal effect was constructed on the surface of titanium by chemical vapor deposition(CVD)interface engineering.The Ti-RP can significantly increase the temperature under US radiation after combine with nitric oxide(NO)to effectively eradicate multidrug-resistant Staphylococcus aureus(MRSA)infection on the surface of the titanium implant efficiently.This paper is divided into three parts:1.Construction of Ti-RP heterojunction interface and sono-thermal tests.RP was transformed by CVD to form a compact film on titanium surface.Characterizations showed that the Ti-RP heterojunction interfaces were successfully constructed on the surface of Ti.And temperature changes of samples under US radiation were recorded by infrared thermal imager.Corresponding results of tests showed that the interface engineering successfully endows Ti with the ability of sono-thermal effect(over20 °C)under US radiation.2.Mechanism and characteristics of the sono-thermal effect of Ti-RP.Based on the theories of acoustoelectric effect,a series of electrochemical and directional tests were carried out to verify that the mechanism of sono-thermal effect of Ti-RP.The test results showed the underlying mechanism was related to the motions of electrons/ phonons excited by US.Meanwhile,more different samples with significant sono-thermal abilities were obtained by CVD proving that this interface engineering strategy of endowing metal with sono-thermal effect was universal.3.Construction and application of the synergistic antibacterial system involed Ti-RP and NO.The sono-thermal biomaterial,Ti-RP,was further modified with a functionalized coating with NO-gas release to realize synergetic antibacterial therapy towards multidrug-resistant bacterial infection.In addition,the results of biocompatibility test in vitro and histopathological analysis in vivo all showed that this controlled sono-thermal effect did not cause any thermal damage,which was a mild,reliable and efficient treatment strategy. |
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