Tissue-Adhesive Endoscopic Tattoo Inks for Precise Marking and Surveillance of Gastrointestinal Lesions

Abstract

Accurate marking of lesions and polyps is essential for effective management of gastrointestinal (GI) diseases, including colorectal cancer. Existing FDA-approved endoscopic carbon suspensions diffuse extensively within tissue and can extravasate intraperitoneally, compromising lesion localization, increasing fibrosis risk, and triggering inflammatory responses. These limitations reduce surgical precision and adversely affect patient outcomes. Here, we developed Tissue Adhesive Tattoos, generation 2 (TAT2) inks, composed of iron oxide nanoparticles encapsulated in bioadhesive polymers to improve spatial accuracy while maintaining high endoscopic contrast. TAT2 inks exhibit easy injectability, long-term stability, low macrophage inflammation, and strong spatial localization in ex vivo porcine intestinal tissue. Compared to clinical carbon ink, which spreads widely, TAT2 inks remained sharply localized with excellent contrast after submucosal injection in live mice and pigs. TAT2 also enabled visualization from both luminal and serosal surfaces and supported precise quadrant marking. Additionally, TAT2 inks were MR-compatible, expanding multimodality. Overall, TAT2 inks are biocompatible, non-inflammatory, precisely localized, and improve endoscopic marking for GI disease. TeaserEngineered bioadhesive tattoo inks deliver precise, durable GI marking with minimal spread and compatibility across imaging modalities.