The objective of this project is to study the analytical performance benefits of nitric oxide (NO)-releasing percutaneously implanted glucose sensors in a diabetic swine model as a function of NO-release duration. Continuous glucose monitoring (CGM) devices with superior usability (i.e., for immediate use and extended duration) would greatly increase the ability of those afflicted with diabetes to successfully manage their disease. We have demonstrated in a non-diabetic (i.e., healthy) swine model that NO- releasing sensor membranes both lessen the FBR and facilitate improved analytical sensor performance up to 10 days-the longest duration evaluated. However, CGM devices are intended for diabetic use and longer implantation periods would improve device utility/value. The variance in FBR and in vivo sensor performance among healthy and diabetic subjects is currently unknown but likely large due to impaired physiology and lower endogenous NO production. We hypothesize that the improvements in FBR and sensor performance that we have observed via exogenous (i.e., polymeric) NO release in healthy animals will be even greater in diabetic subjects. Through our work, we will study the influence of extended NO release on tissue biocompatibility and sensor performance as a function of diabetes. In this respect, we will generate new knowledge on how diabetes influences the FBR and in vivo sensor performance.

Public Health Relevance

The objective of this proposal is to study the foreign body response and analytical sensor performance benefits of nitric oxide-releasing percutaneous glucose biosensors in healthy and diabetic swine. Our hypothesis is that the performance benefits of sensors that slowly release nitric oxide-particularly for extended periods-will be even greater in diabetic animals due to inherently lower endogenous nitric oxide levels. The research has the potential to expand blood glucose monitoring compliance by improving the reliability and operational lifetime of continuous glucose monitoring devices.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK108318-04
Application #
9606477
Study Section
Instrumentation and Systems Development Study Section (ISD)
Program Officer
Arreaza-Rubin, Guillermo
Project Start
2015-12-01
Project End
2019-11-30
Budget Start
2018-12-01
Budget End
2019-11-30
Support Year
4
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Soto, Robert J; Merricks, Elizabeth P; Bellinger, Dwight A et al. (2018) Influence of diabetes on the foreign body response to nitric oxide-releasing implants. Biomaterials 157:76-85
Soto, Robert J; Yang, Lei; Schoenfisch, Mark H (2016) Functionalized Mesoporous Silica via an Aminosilane Surfactant Ion Exchange Reaction: Controlled Scaffold Design and Nitric Oxide Release. ACS Appl Mater Interfaces 8:2220-31