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

Abstract

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.

Design of a Sandwich Hierarchically Porous Membrane with Oxygen Supplement Function for Implantable Glucose Sensor

“…Improving the loading enzyme capacity of the electrode [51][52][53][54], optimizing the immobilization methods [55] and enhancing enzyme activity [32,46] of GOD can slow down the degradation rate of the enzyme. The anti-inflammatory effect of nitric oxide and dexamethasone can increase the compatibility of tissue-sensor interface and improve the sensor lifetime [56][57][58][59], but the duration of anti-inflammatory medication is affected by the pore size of membrane. Hence, a coat with anti-inflammatory function can be added to SHPM-OS membrane structure in the future to reduce biofouling-related problems and the speed of electrode fibrosis [18].…”

Microelectrode Biosensors for in vivo Analysis of Brain Interstitial Fluid

“…In diabetes research, when Vallejo‐Heligon et al . coated subcutaneous glucose sensors with a porous polyurethane membrane loaded with dexamethasone, sensor sensitivity was found to be extended over a 21‐day implantation period . However, systemic dexamethasone can induce many side‐effects, including swelling, sleep problems, and/or weight gain.…”

Multicompartment Drug Release System for Dynamic Modulation of Tissue Responses

“…Attempts to modulate the FBR have taken various forms, but some of the most effective have been coating the implants in drug eluting materials. Typically, the drugs used are steroids and are used simply as a way to slow down the inflammatory response to extend sensor lifetimes . We and others believe that more targeted, controlled approaches may have better long‐term outcomes .…”

“…A variety of attempts to mitigate the FBR to implants have centered around delivering drugs or cytokines . Typically, nonspecific anti‐inflammatory drugs are used as a way to reduce the recruitment and activation of inflammatory cells and extend the useful lifetime of implanted materials.…”