Near-Infrared Dye-Loaded Thermosensitive Hydrogels as Novel Fluorescence Tissue Markers

Accurate intraoperative localization of deep-seated lesions remains a major challenge in minimally invasive procedures such as laparoscopic and robotic surgeries. Current marking strategies—including ink tattooing and metallic clips—are limited by dye diffusion, or poor intraoperative visibility. To address these issues, we developed and evaluated four thermosensitive injectable hydrogel systems incorporating indocyanine green-human serum albumin (ICG-HSA) complexes: (1) hexanoyl glycol chitosan (HGC), (2) Pluronic F-127, (3) PCL–PEG–PCL, and (4) PLA–PEG–PLA. All hydrogel formulations exhibited sol–gel transitions at physiological temperatures, facilitating in situ dye entrapment and prolonged fluorescence retention. In vivo fluorescence imaging revealed that HGC and Pluronic F-127 hydrogels retained signals for up to five and two days, respectively. In contrast, polyester-based hydrogels (PCL–PEG–PCL and PLA–PEG–PLA) preserved fluorescence for up to 21–30 days. PLA–PEG–PLA showed the highest signal-to-background ratios and sustained intensity, while PCL–PEG–PCL also achieved long-term retention. These findings suggest that thermosensitive hydrogels incorporating ICG-HSA complexes represent promising tissue marker platforms for real-time, minimally invasive, and long-term fluorescence-guided lesion tracking.