Basement Membrane-Based Glucose Sensor Coatings Enhance Continuous Glucose Monitoring in Vivo

Klueh, Ulrike; Qiao, Yi; Czajkowski, Caroline; Ludzinska, Izabela; Antar, Omar; Kreutzer, Donald L.

doi:10.1177/1932296815598776

Cited by 12 publications

(14 citation statements)

References 35 publications

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“…We have also demonstrated that MΦ can act as metabolic sinks for glucose by depleting local glucose levels in vitro and in vivo and causing anomalous glucose sensor reading (Klueh et al 2014a). These and other studies support our general hypotheses that MΦ recruitment and activation can directly decrease glucose sensor function and CGM performance in vivo (Klueh et al 2010a; Klueh et al 2015; Novak and Reichert 2015; Novak et al 2014). Since the recruitment and accumulation of inflammatory leukocytes to injured tissue is dependent on the local generation of leukocyte chemotactic factors (LCF), we chose to investigate the role of monocyte/macrophage LCF in controlling MΦ recruitment into sensor implantation sites and sensor function (Figure 1).…”

Section: Introductionsupporting

confidence: 89%

Impact of CCL2 and CCR2 chemokine/receptor deficiencies on macrophage recruitment and continuous glucose monitoring in vivo

Klueh

Czajkowski

Ludzinska

et al. 2016

Biosensors and Bioelectronics

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The accumulation of macrophages (MΦ) at the sensor-tissue interface is thought to be a major player in controlling tissue reactions and sensor performance in vivo. Nevertheless until recently no direct demonstration of the causal relationship between MΦ aggregation and loss of sensor function existed. Using a Continuous Glucose Monitoring (CGM) murine model we previously demonstrated that genetic deficiencies of MΦ or depletion of MΦ decreased MΦ accumulation at sensor implantation sites, which led to significantly enhanced CGM performance, when compared to normal mice. Additional studies in our laboratories have also demonstrated that MΦ can act as “metabolic sinks” by depleting glucose levels at the implanted sensors in vitro and in vivo. In the present study we extended these observations by demonstrating that MΦ chemokine (CCL2) and receptor (CCR2) knockout mice displayed a decrease in inflammation and MΦ recruitment at sensor implantation sites, when compared to normal mice. This decreased MΦ recruitment significantly enhanced CGM performance when compared to control mice. These studies demonstrated the importance of the CCL2 family of chemokines and related receptors in MΦ recruitment and sensor performance and suggest chemokine targets for enhancing CGM in vivo.

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Section: Introductionsupporting

confidence: 89%

Impact of CCL2 and CCR2 chemokine/receptor deficiencies on macrophage recruitment and continuous glucose monitoring in vivo

Klueh

Czajkowski

Ludzinska

et al. 2016

Biosensors and Bioelectronics

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“…Aseptic techniques were utilized during the coating process and before implantation. To coat the glucose sensors with crosslinked BM, the glucose sensors were placed on a sterile polytetrafluoroethylene (PTFE) liner by modification of our previously described methods . Specifically, 50 μL of dialyzed Cultrex (15 mg protein/mL) was applied on one side of each sensor and placed in a 37°C incubator for 2 h (Fig.…”

Section: Methodsmentioning

confidence: 99%

“…Once it was established that sensor coating did not negatively impact sensor performance in vitro , we evaluated the performance of the X‐Cultrex‐coated sensors versus uncoated sensors in our CGM mouse model . Cultrex‐ and X‐Cultrex‐coated and noncoated sensors were implanted in CD‐1 mice (Jackson Laboratory, Bar Harbor, ME) and CGM was undertaken for a period up to 28 days as described previously . Blood glucose reference measurements from the tail vein were obtained over the 28‐day implantation period using Bayer Contour blood glucose monitors.…”

Section: Methodsmentioning

confidence: 99%

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

Klueh

Ludzinska

Czajkowski

et al. 2017

J Biomedical Materials Res

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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.

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“…These include improvements in CGM signal filtering, denoising, and enhancement that resulted in significantly better sensor performance. 9 Furthermore, reduction of biofouling and enzyme degradation can reduce signal error and improve reliability and longevity of CGM, 10,11 as well as standardized and less traumatic sensor insertion. 10 Although a consensus guideline was proposed in 2008, 12 the scientific community has yet to agree upon how to best assess CGM accuracy.…”

Section: -6mentioning

confidence: 99%

Future of Automated Insulin Delivery Systems

Castle

DeVries

Kovatchev

2017

Diabetes Technology & Therapeutics

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Advances in continuous glucose monitoring (CGM) have brought on a paradigm shift in the management of type 1 diabetes. These advances have enabled the automation of insulin delivery, where an algorithm determines the insulin delivery rate in response to the CGM values. There are multiple automated insulin delivery (AID) systems in development. A system that automates basal insulin delivery has already received Food and Drug Administration approval, and more systems are likely to follow. As the field of AID matures, future systems may incorporate additional hormones and/or multiple inputs, such as activity level. All AID systems are impacted by CGM accuracy and future CGM devices must be shown to be sufficiently accurate to be safely incorporated into AID. In this article, we summarize recent achievements in AID development, with a special emphasis on CGM sensor performance, and discuss the future of AID systems from the point of view of their input-output characteristics, form factor, and adaptability.

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Basement Membrane-Based Glucose Sensor Coatings Enhance Continuous Glucose Monitoring in Vivo

Abstract: Basement-membrane-based sensor coatings enhance glucose sensor function in vivo, by minimizing or preventing sensor-induced tissues reactions.

Cited by 12 publications

References 35 publications

Impact of CCL2 and CCR2 chemokine/receptor deficiencies on macrophage recruitment and continuous glucose monitoring in vivo

Impact of CCL2 and CCR2 chemokine/receptor deficiencies on macrophage recruitment and continuous glucose monitoring in vivo

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

Future of Automated Insulin Delivery Systems

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