Glucose Sensor Membranes for Mitigating the Foreign Body Response

Abstract

Continuous glucose monitoring devices remain limited in their duration of use due to difficulties presented by the foreign body response (FBR), which impairs sensor functionality immediately following implantation via biofouling and leukocyte infiltration. The FBR persists through the life of the implant, culminating with fibrous encapsulation and isolation from normal tissue. These issues have led researchers to develop strategies to mitigate the FBR and improve tissue integration. Studies have often focused on abating the FBR using various outer coatings, thereby changing the chemical or physical characteristics of the sensor surface. While such strategies have led to some success, they have failed to fully integrate the sensor into surrounding tissue. To further address biocompatibility, researchers have designed coatings capable of actively releasing biological agents (e.g., vascular endothelial growth factor, dexamethasone, and nitric oxide) to direct the FBR to induce tissue integration. Active release approaches have proven promising and, when combined with biocompatible coating materials, may ultimately improve the in vivo lifetime of subcutaneous glucose biosensors. This article focuses on strategies currently under development for mitigating the FBR.

In vivo continuous and simultaneous monitoring of brain energy substrates with a multiplex amperometric enzyme-based biosensor device

“…Although outer membranes are typically self-assembled monolayers on top of the existing enzymatic membrane (Nafion or polyurethane) (Moussy et al, 1993;Vaddiraju et al, 2011), the use of hollow microdialysis membranes in in vivo biosensor applications has also been reported (Koh et al, 2011;Leegsma-Vogt et al, 2001. In addition, the use of a membrane on top of the enzyme layer is an effective anti-biofouling strategy .…”

In Vivo Analytical Performance of Nitric Oxide-Releasing Glucose Biosensors

“…1,2 Insertion of the sensor damages vascularized tissue and results in a cascade of inflammatory events, many of which negatively impact glucose measurements. 3 For example, the resulting passive adsorption of biomolecules (mainly <15 kDa protein fragments) to the sensor surface initiates an inflammatory response and is responsible for a dramatic decrease in sensor sensitivity (∼50%) following sensor implantation.…”

Closed-Loop System in the Management of Diabetes: Past, Present, and Future

“…Additional research is occurring to reduce this biofouling by use of special membrane or sensor materials that limit inflammation or using a sensor membrane coated with anti-inflammatory drugs to reduce inflammation at the site of sensor insertion. 95 Also, the invasiveness of the sensors results in skin-related adverse events, and hence research is continuing for a noninvasive CGM using different techniques such as iontophoresis, bioimpedance spectroscopy, near-infrared spectroscopy, reverse iontophoresis, and sonophoresis. 96 Another problem with the current CGMs is that the sensors last up to 7 days.…”