In a research program now in progress, polymeric materials that catalyze the generation of nitric oxide (NO) at low concentrations are being developed and tested for utility as coatings on surgically implantable amperometric glucose sensors. Heretofore, efforts to develop subcutaneous sensors for real-time clinical monitoring of glucose concentrations in diabetic patients have been stymied by inflammatory/foreign-body responses to implantation of sensors. The present research program follows from an observation, made in a related prior research program, that local generation of NO at low concentrations enhances the biocompatibility of implanted sensors by reducing inflammatory responses.

The Inflammatory Response of Rats to implantation of sham devices was quantified as the normalized value of the fraction of implanted-device area coated with inflammatory marker cells at 7 days after implantation. The values in the histogram are normalized to the inflammatory response of the devices coated with NO-generating material.

The focus of this research program is, more specifically, to develop new biomedical hydrogel and polyurethane coating materials containing immobilized copper(II) ions or other chemical species (e.g., organoselenium) that act as catalysts for in situ conversion of endogenous nitrosothiol compounds (e.g., nitrosoglutathione and nitrosocysteine) to NO, thereby enabling sustained local generation of NO at the surfaces of the implanted sensors. One of the accomplishments thus far has been the synthesis and characterization of a new material that includes a Cu(II)- cyclen compound covalently attached to a cross-linked poly (2-hydroxy- ethyl methacrylate). This material has been found to generate NO from endogenous nitrosothiols in solution at physiological pH. In preliminary in vivo studies using a lipophilic Cu(II)- cyclen compound blended into a biomedical-grade polyurethane coating material on sham subcutaneous devices implanted in rats, an apparent reduction in inflammatory response was demonstrated (see figure). However, proof that NO is the agent causing the observed improvement has yet to be obtained.

Needle-type subcutaneous glucose sensors that are to be coated with various NO-generating materials are undergoing development. At the time of reporting the information for this article, it was planned to use these sensors in experiments to determine (1) whether the NO-generating chemistry is compatible with the glucose-sensing chemistry and (2) whether the sensing function is compromised by coating with the NO-generating materials.

This work was done by Mark. E. Meyerhoff of the University of Michigan for the Army Research Laboratory.

This Brief includes a Technical Support Package (TSP).
NO-Generating Coats for Subcutaneous Glucose Sensors

(reference ARL-0037) is currently available for download from the TSP library.

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