The objective of the proposed research is to develop a new class of nitric oxide (NO)-releasing bioanalytical sensors and evaluate their utility for in vivo subcutaneous sensor applications. The concept of using local NO release to enhance the performance of in vivo subcutaneous sensors represents a novel approach to overcoming the difficulties that have thus far prevented the development of reliable in vivo biosensors. Current scientific knowledge regarding the role of NO in angiogenesis, phagocytosis, thrombosis, and wound healing suggests that controlled in situ NO release may effectively help reduce biofouling and increase blood flow to the sensor, thus minimizing physiological responses that tend to diminish the in vivo performance of subcutaneous sensors. Specifically, it is envisioned that slow release of NO locally at the implant site will both a) reduce bacterial adhesion and associated biofouling problems, and b) enhance overall wound healing and the formation of capillaries near the implant site such that analyte diffusion from blood to the sensor electrode is enhanced. The fundamental question to be answered by the proposed research is whether electrochemical bioanalytical sensors that continuously release NO can be prepared with improved biocompatibility without compromising the sensor's analytical response. Thus, we seek to determine if the chemistries required for sustained NO release can be made compatible with the chemistries required for selective and sensitive detection of glucose. In addition, we aim to employ micropatterning methods to create unique sensor architectures that support NO release while retaining superior analytical sensitivity. The versatility of the sol-gel process in terms of tuning NO release properties by varying the amount of aminosilane, combined with the variety of pattern geometries that may be created using micropatterning techniques, will allow for the development of numerous types of heterogeneous NO-releasing surfaces with a broad range of possible applications. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
5R01EB000708-03
Application #
6789983
Study Section
Special Emphasis Panel (ZRG1-SSS-F (02))
Program Officer
Lee, Albert
Project Start
2002-09-25
Project End
2007-08-31
Budget Start
2004-09-01
Budget End
2005-08-31
Support Year
3
Fiscal Year
2004
Total Cost
$326,045
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
Lu, Yuan; Slomberg, Danielle L; Schoenfisch, Mark H (2014) Nitric oxide-releasing chitosan oligosaccharides as antibacterial agents. Biomaterials 35:1716-24
Brown, Nga L; Rose, Michael B; Blueschke, Gert et al. (2014) Bioburden after Staphylococcus aureus inoculation in type 1 diabetic rats undergoing internal fixation. Plast Reconstr Surg 134:412e-419e
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
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
Lu, Yuan; Slomberg, Danielle L; Sun, Bin et al. (2013) Shape- and nitric oxide flux-dependent bactericidal activity of nitric oxide-releasing silica nanorods. Small 9:2189-98
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
Li, Chenghong (2013) Determination of rate constants of N-alkylation of primary amines by 1H NMR spectroscopy. J Phys Chem A 117:8333-42
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
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

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