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Mixed-Layered Glycodendrimer Probe for Imaging Inflammation at Surgical Site Infections
Anubhav Dhull1, Ki Wan Park2, Aqib Iqbal Dar1
1Department of Chemistry, College of Arts and Sciences, Washington State University, Troy Hall, Rm 222, 1470 E. College Avenue, Pullman, Washington 99164, United States.
Abstract:
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.
Insights
This study introduces a novel dual-fluorescent probe method for real-time differentiation between surgical site infections (SSIs) and inflammation. This technique aids surgeons in accurately identifying and debriding infected tissues, improving patient outcomes.
Area of Science:
- Biomedical Engineering
- Surgical Innovation
- Diagnostic Imaging
Background:
- Surgical site infections (SSIs) are a leading cause of hospital readmissions.
- Accurate differentiation between inflammation and early infection post-surgery is clinically challenging.
- Current methods for intraoperative debridement rely on surgeon experience, risking diagnostic errors.
Purpose of the Study:
- To evaluate the simultaneous use of two fluorescent probes for distinguishing SSIs from inflammation.
- To develop a multiplexed short-wave infrared (SWIR) imaging technique for real-time delineation.
- To assess the probes' efficacy in vitro and in vivo for targeted surgical debridement.
Main Methods:
- Synthesis of maltotriose-indocyanine-green (ICG-DBCO-maltotriose) and 2-deoxyglucose dendrimer (2DG-D) labeled with cyanine 5 (2DG-D-Cy5).
- In vitro evaluation using cell-bacteria coculture models.
- In vivo assessment in a murine implant SSI model utilizing multiplexed SWIR imaging.
Main Results:
- 2DG-D-Cy5 specifically labeled macrophages associated with inflammation in vitro.
- Multiplexed SWIR imaging successfully differentiated infection from inflammation in real time in vivo.
- The dual-probe system enabled precise identification of infected areas for targeted debridement.
Conclusions:
- Simultaneous use of ICG-DBCO-maltotriose and 2DG-D-Cy5 probes allows real-time differentiation of SSIs and inflammation.
- This approach enhances diagnostic confidence and supports targeted surgical intervention.
- The developed technique holds potential for improving surgical outcomes and monitoring therapeutic responses.

