Research Mentor Name

Dr. Ulrike Klueh, Ph.D.

Research Mentor Email Address

Klueh@wayne.edu

Institution / Department

Wayne State University, Biomedical Engineering

Document Type

Research Abstract

Research Type

basicbio

Level of Research

no

Abstract

Background and Aims: Subcutaneous continuous glucose monitoring (CGM) devices serve an important role in diabetes management but are prone to biofouling and ensuant device failure. CGM Implantation of CGM devices incites an inflammatory response with initial skin penetration. One specific response is NETosis, in which leukocytes, (e.g. neutrophils), release nuclear DNA to ensnare foreign antigens designated. This study aimed to determine the factors responsible for CGM-induced NETosis.

Methods: In vitro commercial Libre 2 glucose sensors were evaluated for their ability to induce NETosis. These studies utilized flow cytometry and time-lapse imaging, multiplex cytokine panel assessment, and scanning electron microscope to evaluate cellular morphology in human neutrophils. Immunohistopathologic evaluations for NETosis, inflammation, fibrosis, and neovascularization at device sites were conducted in murine and swine models.

Results: In vitro studies demonstrated that sensor-induced cell death and NETosis is dependent on both the disease state and cell isolation method. Mouse studies demonstrated that the influx of inflammatory cells is augmented in the presence of these devices following priming of the surgical site. NET formation was confirmed in both animal models and was particularly evident following sensor insertion into swine tissue. Chronic inflammation, fibrosis, and blood vessel regression were observed post-7-day insertion.

Conclusion: Glucose sensors induce TRAP formation and augment inflammation. Severe tissue reactions occurred almost immediately following sensor insertion and persisted for the duration of the study (21 days). Maintaining tissue integrity following CGM device insertion will require mitigation of the inflammatory response including NETosis.

Disciplines

Medicine and Health Sciences

Comments

Special acknowledgments to Li Mao Ph.D. for her lab work that makes this project possible.

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