Modulation of the foreign body response to implanted sensor models through device-based delivery of the tyrosine kinase inhibitor, masitinib.

The host foreign body response (FBR) adversely effects the performance of numerous implanted biomaterials especially biosensors, including clinically popular glucose-monitoring sensors. Reactive formation of a fibrous capsule around implanted sensors hinders the transport of essential analytes to the sensor from the surrounding tissue, resulting in loss of glucose response sensitivity and eventual sensor failure. Several strategies have sought to mitigate the foreign body response's effects on CGM sensors through the use of local delivery of pharmaceuticals and biomolecules with limited success. This study describes release of a tyrosine kinase inhibitor - masitinib - from the sensor implant to target tissue resident mast cells as key mediators of the FBR. Model implants are coated with a composite polymer hydrophilic matrix that rapidly dissolves upon tissue implantation to deposit slower-degrading polymer microparticles containing masitinib. Matrix dissolution limits coating interference with sensor function while establishing a local controlled-release delivery depot formulation to alter implant tissue pharmacology and addressing the FBR. Drug efficacy was evaluated in a murine subcutaneous pocket implant model. Drug release extends to more than 30 days in vitro. The resulting FBR in vivo, evaluated by implant capsule thickness and inflammatory cell densities at 14, 21, and 28 days, displays statistically significant reduction in capsule thickness around masitinib-releasing implant sites compared to control implant sites.

Effect of temperature changes on the performance of ionic strength biosensors based on hydrogels and pressure sensors.

Stimuli responsive hydrogels show a strong ability to change in volume with changes in selected environmental properties. This tendency of these hydrogels to change in volume is captured as pressure-change in confined cavities of pressure sensors. An array of pressure sensors on a single chip may carry hydrogels sensitive to multiple, selected metabolic markers and continuously monitor multiple vital parameters simultaneously. Currently, such sensors are capable of continuously monitoring pH, ionic strength, glucose levels and temperature in the sensor environment. In this paper, we report the effect of temperature changes on the performance of ionic strength sensor. A formulation of hydrogel that renders it sensitive to changes in ionic strength was UV polymerized in situ in piezoresistive pressure sensors with different membrane sizes. The sensor sensitivity, response time and stability are investigated as a function of temperature in vitro. The effect of temperature on these sensor characteristics is discussed.

Smart hydrogel based microsensing platform for continuous glucose monitoring.

In this paper, we present preliminary results showing the response of glucose-sensitive hydrogels, confined in micro-pressure sensors, to the changes in environmental glucose concentration. The glucose concentrations were incrementally varied between 20 and 0mM in 0.15M PBS solution at 7.4 pH and bovine serum at 7.4 pH at room temperature and response of the sensor was recorded. The micro sensors demonstrate a response time of 10 minutes in both PBS and serum. Tissue response after 55 days of subcutaneous implantation of a EtO sterilized sensor in mice is presented. The preliminary analysis of the surrounding tissue shows inflammation which is believed not to interfere with the sensor performance.