Although the release of nitric oxide (NO) from biomaterials has been shown to reduce the foreign body response (FBR), the optimal NO release kinetics and doses remain unknown. Herein, polyurethane-coated wire substrates with varying NO release properties were implanted into porcine subcutaneous tissue for 3, 7, 21 and 42 d. Histological analysis revealed that materials with short NO release durations (i.e., 24 h) were insufficient to reduce the collagen capsule thickness at 3 and 6 weeks, whereas implants with longer release durations (i.e., 3 and 14 d) and greater NO payloads significantly reduced the collagen encapsulation at both 3 and 6 weeks. The acute inflammatory response was mitigated most notably by systems with the longest duration and greatest dose of NO release, supporting the notion that these properties are most critical in circumventing the FBR for subcutaneous biomedical applications (e.g., glucose sensors).

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.