Foreign Body Reaction to Implantable Biosensors

Abstract

Background: Implantable biosensors for continuous glucose monitoring can greatly improve diabetes management. However, their applications are still associated with some challenges and one of these is the gradual functionality loss postimplantation as a consequence of the foreign body response (FBR). Sensor miniaturization in combination with drug-eluting biocompatible coatings is a promising strategy to enhance in vivo performance. However, limited study has been performed to understand the effect of initial trauma and implant size on foreign body reaction as well as in vivo performance of implantable glucose sensors. Methods: Different initial trauma was induced by implanting composite coated dummy sensors into rats using various sized needles and 3 different-sized dummy sensors were implanted to examine the size effect. Histological evaluation was performed to relate the inflammatory cell counts and foreign body capsule thickness with the implantation needle size and sensor size respectively. The effect of biocompatible coating on the performance of implantable glucose sensors was determined using both coated amperometric glucose sensors and microdialysis probes. Results: The results revealed that the degree of acute inflammation was mainly controlled by the extent of the initial trauma: the greater the trauma, the greater the acute inflammatory response. Implant size did not affect the acute inflammatory phase. However, the extent of chronic inflammation and fibrous encapsulation were affected by sensor size: the smaller the size the less the extent of chronic inflammation and fibrous encapsulation. Glucose sensors implanted using 14 gauge needles showed significantly lower initial in vivo response compared to those implanted using 16 gauge needles. This was not observed for sensors with dexamethasone-eluting biocompatible coatings since inflammation was suppressed. Conclusions: The results of the current study indicate that the extent of the inflammatory response post–sensor implantation varies as a function of the initial tissue trauma as well as the sensor size. Accordingly, miniaturization of implantable biosensors together with the utilization of a drug-eluting biocompatible composite coating may be a promising strategy to achieve long-term reliable continuous glucose monitoring.

Foreign Body Reaction to Implanted Biomaterials and Its Impact in Nerve Neuroprosthetics

“…FBR is fundamentally tied to tissue trauma (Wang et al, 2015;Klopfleisch and Jung, 2017). Not only is the initial implantation of a device the trigger that begins the cellular events leading to FBR, but subsequent trauma around the implanted device leads to further inflammation and worsens ongoing FBR.…”

Real-time intradermal continuous glucose monitoring using a minimally invasive microneedle-based system

“…Therefore, microneedle-based CGMS are gaining attention because of their reduced invasiveness (Invernale et al 2014 ; Miller et al 2012 , 2016b ), resulting in a virtually painless insertion procedure and a reduced tissue trauma and inflammation (Ventrelli et al 2015 ). The size of a transdermally implanted device affects the tissue trauma during insertion and the degree of inflammation over time, both of which cause an increased foreign body reaction that can be detrimental for long-term measurements (El-Laboudi et al 2013 ; Wang et al 2015 ). Moreover, microneedles shorter than 1 mm, which is the average depth of the dermis in the human forearm (Hwang et al 2016 ), allow direct access to the dermal interstitial fluid.…”

Skin-Integrated Wearable Systems and Implantable Biosensors: A Comprehensive Review

“…The negative FBR of the body involves a cascade of events, including typical wound healing response, acute inflammation, chronic inflammation, and the formation of granulomatous tissue and eventually excessive fibrosis [69,70]. Firstly, when a tissue/device interface is created, the nonspecific blood and tissue fluids proteins adhere onto the surface or invade the materials.…”