Mixed-Layered Glycodendrimer Probe for Imaging Inflammation at Surgical Site Infections

Surgical site infections (SSIs) remain the most common cause for readmission following surgery and are associated with significant medical comorbidities. Distinguishing between inflammation and early infection postsurgery is a critical challenge for clinicians. Intraoperative surgical debridement of infectious tissues relies heavily on the surgeon's experience, risking error due to difficulty in distinguishing infection from inflammation. We evaluated the simultaneous use of two fluorescent probes, maltotriose-indocyanine-green (ICG-DBCO-maltotriose) and a mixed-layered 2-deoxyglucose dendrimer (2DG-D) labeled with cyanine 5 (2DG-D-Cy5), to delineate between SSI and inflammation in vitro in cell-bacteria coculture and in vivo in an early implant SSI model via multiplexed short-wave infrared (SWIR) imaging. To our knowledge, this study is the first to use multiple fluorescent dyes combined with small molecules and dendrimer-based nanoprobes to differentiate between inflammation and infection within the same experimental model. We synthesized 2DG-D using a convergent method, simplifying synthesis and purification. 2DG-D-Cy5 exclusively labeled the macrophages associated with inflammation in vitro. In vivo SWIR imaging using both probes in a murine implant infection model successfully distinguished infection from inflammation in real time, allowing targeted surgical debridement. This real-time detection of infection and inflammation may enhance diagnostic confidence and aid in the monitoring of therapeutic responses.