Porous, Dexamethasone-loaded polyurethane coatings extend performance window of implantable glucose sensors in vivo

• Published in: Acta biomaterialia 2016-01, Vol.30, p.106-115
• Main Authors: Vallejo-Heligon, Suzana G., Brown, Nga L., Reichert, William M., Klitzman, Bruce
• Format: Article
• Language: English
• Subjects: Animal models; Animals; Biocompatibility; Biomedical materials; Blood Glucose - analysis; Blood Glucose - metabolism; Coated Materials, Biocompatible - chemistry; Coated Materials, Biocompatible - pharmacology; Coatings; Dexamethasone - chemistry; Dexamethasone - pharmacology; Electrodes, Implanted; Foreign body response; Glucose; Glucose sensors; In vivo testing; In vivo tests; Inflammation; Male; Materials Testing; Polyurethanes - chemistry; Polyurethanes - pharmacology; Porosity; Rats; Rats, Sprague-Dawley; Sensors; Surgical implants
• ISSN: 1742-7061; 1878-7568
• DOI: 10.1016/j.actbio.2015.10.045

[Display omitted] Continuous glucose sensors offer the promise of tight glycemic control for insulin dependent diabetics; however, utilization of such systems has been hindered by issues of tissue compatibility. Here we report on the in vivo performance of implanted glucose sensors coated with Dexamethasone-loaded (Dex-loaded) porous coatings employed to mediate the tissue-sensor interface. Two animal studies were conducted to (1) characterize the tissue modifying effects of the porous Dex-loaded coatings deployed on sensor surrogate implants and (2) investigate the effects of the same coatings on the in vivo performance of Medtronic MiniMed SOF-SENSOR™ glucose sensors. The tissue response to implants was evaluated by quantifying macrophage infiltration, blood vessel formation, and collagen density around implants. Sensor function was assessed by measuring changes in sensor sensitivity and time lag, calculating the Mean Absolute Relative Difference (MARD) for each sensor treatment, and performing functional glucose challenge test at relevant time points. Implants treated with porous Dex-loaded coatings diminished inflammation and enhanced vascularization of the tissue surrounding the implants. Functional sensors with Dex-loaded porous coatings showed enhanced sensor sensitivity over a 21-day period when compared to controls. Enhanced sensor sensitivity was accompanied with an increase in sensor signal lag and MARD score. These results indicate that Dex-loaded porous coatings were able to elicit an attenuated tissue response, and that such tissue microenvironment could be conducive towards extending the performance window of glucose sensors in vivo. In the present article, a coating to extend the functionality of implantable glucose sensors in vivo was developed. Our study showed that the delivery of an anti-inflammatory agent with the presentation of micro-sized topographical cues from coatings may lead to improved long-term glucose sensor function in vivo. We believe that improved function of sensors treated with the novel coatings was a result of the observed decreases in inflammatory cell density and increases in vessel density of the tissue adjacent to the devices. Furthermore, extending the in vivo functionality of implantable glucose sensors may lead to greater adoption of these devices by diabetic patients.