Crosslinked basement membrane‐based coatings enhance glucose sensor function and continuous glucose monitoring in vivo

Abstract

Overcoming sensor-induced tissue reactions is an essential element of achieving successful continuous glucose monitoring (CGM) in the management of diabetes, particularly when used in closed loop technology. Recently, we demonstrated that basement membrane (BM)-based glucose sensor coatings significantly reduced tissue reactions at sites of device implantation. However, the biocompatible BMbased biohydrogel sensor coating rapidly degraded over a less than a 3-week period, which effectively eliminated the protective sensor coating. In an effort to increase the stability and effectiveness of the BM coating, we evaluated the impact of crosslinking BM utilizing glutaraldehyde as a crosslinking agent, designated as X-Cultrex. Sensor performance (nonrecalibrated) was evaluated for the impact of these X-Cultrex coatings in vitro and in vivo. Sensor performance was assessed over a 28-day time period in a murine CGM model and expressed as mean absolute relative difference (MARD) values. Tissue reactivity of Cultrex-coated, X-Cultrex-coated, and uncoated glucose sensors was evaluated over a 28-day time period in vivo using standard histological techniques. These studies demonstrated that X-Cultrex-based sensor coatings had no effect on glucose sensor function in vitro. In vivo, glucose sensor performance was significantly enhanced following X-Cultrex coating throughout the 28-day study. Histological evaluations of X-Cultrex-treated sensors demonstrated significantly less tissue reactivity when compared to uncoated sensors.

Near-infrared fluorescent coatings of medical devices for image-guided surgery

“…Functional coatings are particularly useful in the medical field for the prevention of microbial colonization on implants [8] and medical devices [9][10][11][12][13], to ensure drug delivery and sustained release of bioactive agents [14][15][16][17][18] as well as to minimize protein adsorption on medical devices [19]. Polymeric coatings containing fluorescent dyes are interesting for many applications including optical sensors [20][21][22][23], stimuli responsive smart materials [24][25][26], and, ultimately, in medical imaging and fluorescence-guided surgery [27][28][29][30]. Currently, the medical field is mainly dominated by other imaging modalities, such as X-ray radiography, computed tomography (CT), magnetic resonance imaging (MRI), ultra-sonography, positron emission tomography (PET), etc., but they have several limitations [31].…”

Macrophage microRNA-146a is a central regulator of the foreign body response to biomaterial implants

“…The molecular mechanisms driving the FBR remain largely elusive, presenting a significant challenge in medical science. Strategies to mitigate FBR to biomaterials and devices have included various approaches, such as coating devices with basement membrane-derived hydrogels, localized administration of steroids and growth factors, employing alginate-based and zwitterionic material-based hydrogels, and identifying novel molecular targets (20, 64–70). While these methods have shown promise, the results are sometimes inconsistent or contradictory, as documented in various studies (20, 64–70).…”

Continuous Glucose Monitoring Devices: Past, Present, and Future Focus on the History and Evolution of Technological Innovation

“…Both of these tissue reactions compromise sensor function in vivo: inflammation by inducing sensor damage and/or glucose consumption at the sensor site and fibrosis by inducing blood vessel regression thus compromising diffusion in the interstitial fluid of the sensors located in the subcutaneous space. 9,29,[32][33][34][35][36] Given the need to increase sensor performance usage time beyond its current FDA-approved lifespan, transdermal sensors designed to last beyond one to two weeks as developed by DexCom, Abbott Diabetes Care, and Medtronic/MiniMed must address additional parameters. These include ensuring adequate skin adhesion of these devices while simultaneously preventing injury to the epithelial dermis layer.…”

“…More recent research has been directed toward developing device coatings that are less likely to incite a robust FBR. Cell and Molecular Engineering LLC (CMTE, Avon, CT, United States) aims to incorporate tissue response modifiers into basement membrane matrix coatings in an attempt to induce tissue tolerance 33,48 and allow repetitive use of the same insertion site. Clinical Sensors, Inc. (Research Triangle, NC, United States) employed a different approach by designing a nitric oxide-releasing polymer sensor coating designed to enhance sensor accuracy and longevity.…”