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

Abstract

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.