The objective of this proposal is to explore the use of novel NO releasing sensor membranes for developing improved subcutaneous glucose biosensors that function more reliably in vivo. The concept of using local NO release to enhance the performance of in vivo subcutaneous sensors represents a novel approach that may overcome the key obstacles that have prevented the development of in vivo biosensors that function reliably once implanted in patients. Current scientific knowledge regarding the role of NO in angiogenesis, phagocytosis, thrombosis, and wound healing suggests that the controlled release of NO at a sensor interface may increase blood flow to the sensor, reduce inflammation, and promote wound healing by inhibiting bacterial adhesion and minimizing the thickness of the ensuing capsule. Favorable biocompatibility thus may minimize host physiological responses such that the in vivo performance of current subcutaneous biosensors would be dramatically improved. Following the synthesis of NO-releasing sensor membranes with adequate analyte permeability and a wide range of NO release characteristics including flux and duration, we will: 1) evaluate the tissue biocompatibility of such materials in vivo as a function of NO release properties;2) fabricate functional NO-releasing glucose microsensors;3) evaluate the in vivo analytical performance of such sensors in a pig model. The proposed research has the potential to lead to implantable glucose sensors that exhibit reduced biofouling and bacterial infection, enhanced wound healing, and improved analytical performance. A functional glucose sensor with these characteristics would impact millions of diabetic patients who are potential candidates for continuous glucose monitoring devices.

Public Health Relevance

The objective of this proposal is to explore the use of novel nitric oxide (NO)-releasing sensor membranes for developing improved subcutaneous glucose biosensors that function more reliably in vivo. The proposed research has the potential to lead to implantable glucose sensors that exhibit reduced biofouling and bacterial infection, enhanced wound healing, and improved analytical performance.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
5R01EB000708-08
Application #
7759565
Study Section
Enabling Bioanalytical and Biophysical Technologies Study Section (EBT)
Program Officer
Korte, Brenda
Project Start
2002-09-25
Project End
2012-01-31
Budget Start
2010-02-01
Budget End
2011-01-31
Support Year
8
Fiscal Year
2010
Total Cost
$327,428
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
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Soto, Robert J; Privett, Benjamin J; Schoenfisch, Mark H (2014) In vivo analytical performance of nitric oxide-releasing glucose biosensors. Anal Chem 86:7141-9
Nichols, Scott P; Koh, Ahyeon; Storm, Wesley L et al. (2013) Biocompatible materials for continuous glucose monitoring devices. Chem Rev 113:2528-49
Koh, Ahyeon; Lu, Yuan; Schoenfisch, Mark H (2013) Fabrication of nitric oxide-releasing porous polyurethane membranes-coated needle-type implantable glucose biosensors. Anal Chem 85:10488-94
Koh, Ahyeon; Carpenter, Alexis W; Slomberg, Danielle L et al. (2013) Nitric oxide-releasing silica nanoparticle-doped polyurethane electrospun fibers. ACS Appl Mater Interfaces 5:7956-64
Li, Chenghong (2013) Determination of rate constants of N-alkylation of primary amines by 1H NMR spectroscopy. J Phys Chem A 117:8333-42
Lu, Yuan; Slomberg, Danielle L; Shah, Anand et al. (2013) Nitric oxide-releasing amphiphilic poly(amidoamine) (PAMAM) dendrimers as antibacterial agents. Biomacromolecules 14:3589-98
Storm, Wesley L; Schoenfisch, Mark H (2013) Nitric oxide-releasing xerogels synthesized from N-diazeniumdiolate-modified silane precursors. ACS Appl Mater Interfaces 5:4904-12
Nichols, Scott P; Schoenfisch, Mark H (2013) Nitric oxide-flux dependent bacterial adhesion and viability at fibrinogen-coated surfaces. Biomater Sci 1:

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