"Restauro" strategy: Siderophore-like antibiofilm coating combats prosthetic joint infection and preserves implants via bacterial ferroptosis-like death.

Abstract

Prosthetic joint infection (PJI) treatment failure primarily stems from incomplete biofilm removal and antibiotic resistance. Addressing these challenges, antibiotic-independent antimicrobials become preferred weapons. Meanwhile, iron metabolism provides an area of interest, due to its essentiality in biofilm formation. Tannic acid (TA), a plant-derived polyphenol, whose siderophore-like antibacterial mechanism is first revealed in this study, leading to ferroptosis-like death in planktonic, biofilm and intracellular bacteria via inducing iron overload. Herein, a novel "Restauro" strategy inspired by cultural relic restoration is proposed to construct CMCS-OXG@TA-Fe (COTF) hydrogels antibiofilm coating. Utilizing the rapid gelation of carboxymethyl chitosan (CMCS) and oxidized xyloglucan (OXG), COTF hydrogels load with TA-Fe complexes, whose photothermal effect can significantly enhance the ferroptosis-like death characteristics and effectively decompose the biofilm structure. Furthermore, COTF can reduce M2 macrophages in iron-deficient microenvironments, remodeling immunosuppression. Eventually, a surgical standard operating procedure (SOP) is developed, which simply requires sequentially brushing or spraying the prosthesis with the fore-mentioned four chemical solutions, in order to achieve antibiofilm efficacy and implant preservation. Eventually, validations in acute and chronic PJI models confirm the preventive and therapeutic effects of "Restauro" strategy, hence building a new bridge from bench to bedside for future PJI treatments.