The Self‐Adaptive Nanosystem for Implant‐Related Infections Theranostics via Phase‐Change Driven Anti‐Biofilm and the Enhancement of Immune Memory

Abstract Implant‐related infections (IRIs), characterized by the formation of bacterial biofilms and immunosuppressive microenvironment, are a common but tricky clinical issue. In this study, a self‐adaptive theranostics nanosystem is designed based on phase change material (PCM) for IRIs therapy, which can monitor the severity of infection in real time and automatically provide the most appropriate treatment on demand. The nanosystem called CaAlg/LOD/POD@MNO/FAs (CLPM) is made of the fatty acids (FAs) core with dissolved minocycline (MNO) and the calcium alginate (CaAlg) shell with an immobilized lactate oxidase/pyruvate oxidase (LOD/POD) enzyme‐linked system. When the level of infection is mild (wound temperature < 39 °C), the CLPMs perform a bacteriostatic function by slowly releasing MNO from the solid‐phase FAs core. When the infection deteriorates (wound temperature > 39 °C), the solid‐to‐liquid phase change of FAs not only enables a rapid release of MNO but also disrupts the mechanical strength of the biofilm skeleton doped with CLPM, performing a bactericidal function. In addition, CLPM can reduce the accumulation of bacteria‐derived lactate to address lactate‐induced immunosuppression and enhance immune memory response, thereby inhibiting infection recurrence.