Yan Wang1, Santhisagar Vaddiraju2, Bing Gu1, Fotios Papadimitrakopoulos3, Diane J Burgess4. 1. Department of Pharmaceutical Sciences, University of Connecticut, Storrs, CT, USA. 2. Biorasis Inc, Storrs, CT, USA. 3. Institute of Materials Science, University of Connecticut, Storrs, CT, USA. 4. Department of Pharmaceutical Sciences, University of Connecticut, Storrs, CT, USA d.burgess@uconn.edu.
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.
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.
Authors: C Choleau; J C Klein; G Reach; B Aussedat; V Demaria-Pesce; G S Wilson; R Gifford; W K Ward Journal: Biosens Bioelectron Date: 2002-08 Impact factor: 10.618
Authors: C Choleau; J C Klein; G Reach; B Aussedat; V Demaria-Pesce; G S Wilson; R Gifford; W K Ward Journal: Biosens Bioelectron Date: 2002-08 Impact factor: 10.618
Authors: Robert A Croce; SanthiSagar Vaddiraju; Jun Kondo; Yan Wang; Liang Zuo; Kai Zhu; Syed K Islam; Diane J Burgess; Fotios Papadimitrakopoulos; Faquir C Jain Journal: Biomed Microdevices Date: 2013-02 Impact factor: 2.838
Authors: Lauren M Huyett; Rowena Mittal; Howard C Zisser; Evan S Luxon; Alex Yee; Eyal Dassau; Francis J Doyle; Daniel R Burnett Journal: J Diabetes Sci Technol Date: 2016-08-22
Authors: David K Piech; Benjamin C Johnson; Konlin Shen; M Meraj Ghanbari; Ka Yiu Li; Ryan M Neely; Joshua E Kay; Jose M Carmena; Michel M Maharbiz; Rikky Muller Journal: Nat Biomed Eng Date: 2020-02-19 Impact factor: 25.671