Regulating the Interaction Between Near-Infrared Dye and Endogenous Albumin for Concurrent Imaging Skin Inflammation and Neovascularization After Flap Transplantation

Concurrent imaging of skin inflammation and neovascularization is crucial for diagnosing and monitoring skin conditions, especially in flap transplantation. However, current imaging modalities in the clinic are often non-intuitive, have low resolution, or lack the ability to specifically target skin inflammation. Given that albumin can serve as a biomarker for the disruption of skin-vessel barrier (SVB), probes targeting skin inflammation typically need to specifically bind to endogenous albumin, which often results in high background signals. In this study, we screen a series of near-infrared (NIR) dyes for their in vivo covalent binding capabilities with endogenous albumin, and identify the optimal dye for achieving high-contrast imaging of skin inflammation in models of SVB disruption, with minimal interference from other tissues or organs (e.g., skin and muscle). Moreover, by utilizing an albumin-targeting dye with another albumin-escaping NIR-II dye with a non-overlapping emission wavelength, this work explores the concurrent imaging of skin inflammation and neovascularization after flap transplantation, affording to simultaneously assess skin inflammation and the restoration of blood supply.