Near-Infrared Light Triggered Phototherapy and Immunotherapy for Elimination of Methicillin-Resistant <i>Staphylococcus aureus</i> Biofilm Infection on Bone Implant

Abstract

Clinically, methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) biofilm infection inevitably induces the failure of bone implants. Herein, a hydrophilic and viscous hydrogel of poly(vinyl alcohol) modified with chitosan, polydopamine, and NO release donor was formed on a red phosphorus nanofilm deposited on a titanium implant (Ti-RP/PCP/RSNO). Under the irradiation of near-infrared light (NIR), peroxynitrite (^•ONOO^-) was formed by the reaction between the released NO and superoxide (^•O₂^-) produced by the RP nanofilm. Specifically, we revealed the antibacterial mechanism of the ONOO^- against the MRSA biofilm. In addition, osteogenic differentiation was promoted and inflammatory polarization was regulated by the released NO without NIR irradiation through upregulating the expression of <i>Opn</i> and <i>Ocn</i> genes and TNF-α. The MRSA biofilm was synergistically eradicated by ^•ONOO^-, hyperthermia, and ^•O^2- under NIR irradiation as well as the immunoreaction of the M1 polarization. The <i>in vivo</i> results also confirmed the excellent osteogenesis and biofilm eradication by released NO from the RP/PCP/RSNO system under NIR irradiation, indicating the noninvasive tissue reconstruction of MRSA-infected tissues through phototherapy and immunotherapy.