Biocompatible materials for continuous glucose monitoring devices.

Abstract

Diabetes mellitus is a worldwide epidemic characterized by chronic hyperglycemia that results from either a deficiency or tolerance in insulin.1 In the United States, 8.3% of the population currently has diabetes and that number is projected to increase to 1 in 3 adults by 2050 if current trends continue.2 As a consequence, diabetes is the seventh leading cause of death with an annual cost burden of $174 billion in the United States, including $116 billion in direct medical expenses.2 Blood glucose levels in diabetics fluctuate significantly throughout the day, resulting in serious complications including heart attacks, strokes, high blood pressure, kidney failure, blindness and limb amputation.1–2 Portable glucose sensors give patients the ability to monitor blood glucose levels, manage insulin levels, and reduce the morbidity and mortality of diabetes mellitus. Traditional glucose monitoring techniques are primarily based on the use of electrochemical amperometric glucose sensors. In 1987, Medisense Inc. launched the first personal glucose testing device consisting of a test strip and reader. Over 40 different commercial pocket-sized monitors have been introduced since then.3 To date, the U.S. Food and Drug Administration (FDA) has approved >25 glucose monitors with the majority employing test strips consisting of either glucose dehydrogenase (GDH) or glucose oxidase (GOx) immobilized on a screen-printed electrode.4 The analysis is based on obtaining a small blood sample (<1 μL) through a finger prick that is subsequently introduced into the test strip via capillary action.3–4 While these monitors have augmented the health outcomes for people with diabetes by improving blood glucose management, such monitoring only provides instantaneous blood glucose concentrations that are unable to warn of hyperglycemic or hypoglycemic events in advance. Additionally, the sample collection (i.e., finger prick) method is inconvenient resulting in poor patient compliance. Analytical methods that enable continuous monitoring of blood glucose have thus been sought.5 Continuous glucose monitoring (CGM) provides real-time information on trends (i.e., whether the glucose levels are increasing or decreasing), magnitude, duration, and frequency of glucose fluctuations during the day.5–6 Ideally, analytically functional continuous glucose monitoring devices could be linked to an insulin delivery pump, creating an artificial pancreas.5–6 In this review, we describe progress in the development of continuous glucose monitoring technologies, specifically focusing on subcutaneous implantable electrochemical glucose sensors, which are widely studied and commercially available. We discuss the challenges associated with the development of biocompatible coatings for electrochemical glucose sensors. Borrowing from the ideas of David Williams, we consider sensor coatings to be “biocompatible” if they optimize the clinical relevance of the sensor, avoid any negative local and systemic effects, and elicit the most appropriate local tissue response adjacent to the implant.7