More than 18 million Americans suffer today from insulin-dependent, type II diabetes. It is estimated that half of type II diabetics are unable or unwilling to properly gluco-regulate themselves using the standard finger stick regimen. Many of these people would benefit greatly from an indwelling, closed loop insulin delivery device, e.g. the artificial pancreas that employs a sensor to continuously monitor glucose levels in either blood or interstitial fluid. Although several groups have reported biosensors that have successfully functioned for weeks to months in vivo, no glucose sensor appears capable of reliably and predictably surviving long-term implantation. Consequently, all FDA-approved glucose sensors are deemed suitable for acute applications only. Hypothesis: Our global hypothesis is that the last remaining barrier to the application long-term indwelling of glucose sensors is surviving wound-healing mediated sensor failure. We address this hypothesis by devising and characterizing membrane modifications and local release strategies that (1) resist biofouling, (2) attenuate inflammation, (3) reduce the fibrosity and (4) promote vascularity of the surrounding wound healing tissue will minimize impediments to glucose transport across the sensor membrane. This competitive renewal is divided into translational and experimental objectives. The translational objective is the application of dexamethasone, VEGF and texturing strategies developed in the previous funding cycle to FDA-approved Medtronic Diabetes SOF-SENSORTM glucose sensors. This will include implantation in intact tissue, as well as the first-time use of a dorsal transcutaneous window chamber rat model to directly observe the evolution of tissue architecture in the vicinity immediately adjacent to a subcutaneously implanted sensor. The experimental objectives also examine biomimetic strategies that employ seeded adipose-derived stems cells (ASC) for mediating inflammation and promoting vessel formation in the tissue surrounding implanted sensors. In each case, the experimental results from the window chamber images and the live senor responses will be benchmarked using transport modeling of perfusion of the sensor surface with blood borne glucose. A more precise model will be used to predict the anticipated affects of microvessel density, fibrous encapsulation, and biofouling on the observed sensor response.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
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Biomaterials and Biointerfaces Study Section (BMBI)
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Arreaza-Rubin, Guillermo
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Duke University
Biomedical Engineering
Schools of Engineering
United States
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Vallejo-Heligon, Suzana G; Brown, Nga L; Reichert, William M et al. (2016) Porous, Dexamethasone-loaded polyurethane coatings extend performance window of implantable glucose sensors in vivo. Acta Biomater 30:106-115
Novak, Matthew T; Reichert, William M (2015) Modeling the Physiological Factors Affecting Glucose Sensor Function in Vivo. J Diabetes Sci Technol 9:993-8
Vernekar, Varadraj N; Wallace, Charles S; Wu, Mina et al. (2014) Bi-ligand surfaces with oriented and patterned protein for real-time tracking of cell migration. Colloids Surf B Biointerfaces 123:225-35
Vallejo-Heligon, Suzana G; Klitzman, Bruce; Reichert, William M (2014) Characterization of porous, dexamethasone-releasing polyurethane coatings for glucose sensors. Acta Biomater 10:4629-4638
Novak, Matthew T; Yuan, Fan; Reichert, William M (2014) Macrophage embedded fibrin gels: an in vitro platform for assessing inflammation effects on implantable glucose sensors. Biomaterials 35:9563-72
Reichert, William M (2013) Diversity and the Duke BME PhD program: then, now and moving forward. Ann Biomed Eng 41:2019-26
Novak, Matthew T; Yuan, Fan; Reichert, William M (2013) Predicting glucose sensor behavior in blood using transport modeling: relative impacts of protein biofouling and cellular metabolic effects. J Diabetes Sci Technol 7:1547-60
Harris, James M; Lopez, Gabriel P; Reichert, William M (2012) Silica-dispersed glucose oxidase for glucose sensing: in vitro testing in serum and blood and the effect of condensation pH. Sens Actuators B Chem 174:373-379
Le, Nga N; Rose, Michael B; Levinson, Howard et al. (2011) Implant healing in experimental animal models of diabetes. J Diabetes Sci Technol 5:605-18
Brochu, Alice B W; Craig, Stephen L; Reichert, William M (2011) Self-healing biomaterials. J Biomed Mater Res A 96:492-506

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