Reconfigurable Zwitterionic Polymer Dot-Hydrogel for Decoupled In Situ pH and Temperature Sensing in Dynamic Biological Microenvironments

Abstract

In situ biological systems are continuously exposed to physical (temperature) and chemical (pH) cues, which provide critical inputs for biosensing. However, pathological microenvironments exhibit dynamically intertwined variations in these parameters, necessitating a sensing platform capable of real-time signal transduction and decoupling. Conventional rigid sensors suffer from mechanical mismatch with soft tissues, leading to signal distortion and poor stability. Here, we report a reconfigurable hydrogel platform integrating carbonized polydopamine (cPDA)-loaded zwitterionic polymer dots (Z-PD), conductive Z-PD (cZ-PD), within a thermoresponsive hydrogel for decoupled in situ pH and temperature sensing. The sensing mechanism is dependent on the pH-driven “blooming-bridged” transition of the cZ-PD, which controls cZ-PD distribution, hydrogen bonding, pore structure, and charge transport within the hydrogel matrix. As a result, acidic and basic conditions exhibit significant and reversible alterations in optical, electrical, and mechanical properties relative to physiological pH. Temperature further regulates these responses via the volume phase transition of the hydrogel, enabling tunable electrical behavior across physiologically and therapeutically relevant ranges. Beyond chemical and thermal stimuli, the hydrogel demonstrates multimodal electrical responses to tissue-mimicking pressure, strain, and fluid exposure, generating distinct resistance signatures. The platform maintains stable sensing performance under repeated thermal cycling and in in vitro cellular environments. Collectively, this approach offers a versatile strategy for real-time monitoring of complex pathological microenvironments and advances the development of soft bioelectronic sensors for integrated diagnostic and therapeutic applications.