pH-responsive carborhodol-coupled chitosan-based hydrogels for the detection of wound infection-relevant pH changes

Abstract

Wound infections are typically accompanied by an elevated local pH, resulting from bacterial metabolism. Smart wound dressings capable of sensing and reporting these pH changes could enable clinicians to detect infections at an early stage and begin appropriate treatment. However, conventional pH-responsive dyes often lack photostability and exhibit subtle or ambiguous color changes. In this work, we report the synthesis of two novel carborhodol dyes, AS 14 and AS 15, which exhibit reversible chromogenic and fluorogenic responses within the physiologically relevant pH range 4–7. The NHS-esters of these dyes were covalently coupled to chitosan (CS) films, yielding stable, biopolymer-based sensors. Both AS 14-CS and AS 15-CS films demonstrated high photostability, reversible pH-dependent responses, and distinct fluorescence lifetime changes. Notably, AS 14-CS exhibited dual chromogenic and fluorogenic responses, achieving a fluorescence turn-on ratio of 30 in basic versus acidic form, while AS 15-CS functioned primarily as a chromogenic sensor, exhibiting a color change from pink to blue. By covalently coupling the novel carborhodols, the pH response is stable over time. The possibility of relying on fluorescent lifetime measurements also enable measurement in autofluorescent wound environments, which is not possible for dyes with shorter lifetimes. These pH-responsive films offer a robust and sensitive platform for further development into infection-responsive wound dressings, with AS 14 CS in particular providing dual-mode sensing in one film, enabling both naked-eye visualization and higher-sensitivity fluorescent readouts without requiring any on-patch electronics.