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 sensor membrane porosity, and diabetes state (i.e., insulin versus non-insulin dependent). 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. In the prior funding period, we demonstrated in a non-insulin dependent diabetic swine model that NO-releasing sensor membranes both lessen the FBR and facilitate improved analytical sensor performance up to 28 days?the longest duration evaluated. However, CGM devices are intended for insulin-dependent individuals and longer implantation periods would improve device utility/value. The variance in FBR and in vivo sensor performance for insulin- and non-insulin-dependent subjects is currently unknown but likely significant due to more impaired wound healing mechanisms. We hypothesize that the improvements in FBR and sensor performance that we have reported sensor membranes that release NO for 28 days will be extended to at least two months by using porous sensor membranes that release for 60+ days and passively promote healthy re-vascularization in the proximity of the sensor. Through our work, we will study the influence of both NO release and porosity on tissue biocompatibility and sensor performance as a function of diabetes. In this respect, we will generate new knowledge on how diabetes influences the tissue integration and in vivo sensor performance.

Public Health Relevance

The objective of this proposal is to develop porous nitric oxide (NO)-releasing sensor membranes that further improve the in vivo analytical performance of percutaneous glucose biosensors by mitigating the foreign body response. Our hypothesis is that the combination of nitric oxide release and porosity will result in a sensor membrane that promotes wound healing, tissue integration and thereby extends overall in vivo sensor performance. The research has the potential to expand blood glucose monitoring compliance by improving the reliability of continuous glucose monitoring devices.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
Project #
Application #
Study Section
Enabling Bioanalytical and Imaging Technologies Study Section (EBIT)
Program Officer
Arreaza-Rubin, Guillermo
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of North Carolina Chapel Hill
Schools of Arts and Sciences
Chapel Hill
United States
Zip Code
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