The purpose of this study was to test the hypothesis that porous poly-l-lactic acid (PLLA) sensor coatings reduce fibrosis and promote blood microvessel formation in tissue adjacent to the sensor surface. Porous PLLA coatings were produced using ammonium bicarbonate as the gas foaming/salt leaching agent, and deployed on functional and nonfunctional sensors. The porous coatings minimally affected sensor accuracy and response rate in vitro. Three-week subcutaneous rat studies of nonfunctional glucose sensors showed the anticipated effect of porous coatings enhancing vascularity and decreasing collagen deposition. In contrast, percutaneous functional sensors with and without porous coatings showed no significant difference in terms of histology or sensor response. In spite of the observation that texturing increases the vascularity of the tissue that surrounds implanted sensors, other factors such as the additional mechanical stresses imposed by percutaneous tethering may override the beneficial effects of the porous coatings.
Vascular endothelial growth factor (VEGF) and dexamethasone (DX) release from hydrogel coatings were examined as a means to modify tissue inflammation and induce angiogenesis. Antibiofouling hydrogels for implantable glucose sensor coatings were prepared from 2-hydroxyethyl methacrylate, N-vinyl pyrrolidinone, and polyethylene glycol. Microdialysis sampling was used to test the effect of the hydrogel coating on glucose recovery. VEGF-releasing hydrogel-coated fibers increased vascularity and inflammation in the surrounding tissue after 2 weeks of implantation compared to hydrogel-coated fibers. DX-releasing hydrogel-coated fibers reduced inflammation compared to hydrogel-coated fibers and had reduced capsule vascularity compared to VEGF-releasing hydrogel-coated fibers. Hydrogels that released both VEGF and DX simultaneously also showed reduced inflammation at 2 weeks implantation; however, no enhanced vessel formation was observed indicating that the DX diminished the VEGF effect. At 6 weeks, there were no detectable differences between drug-releasing hydrogel-coated fibers and control fibers. From this study, hydrogel drug release affected initial events of the foreign body response with DX inhibiting VEGF, but once the drug depot was exhausted these effects disappeared.
To date, there have been a number of cases where glucose sensors have performed well over long periods of implantation; however, it remains difficult to predict whether a given sensor will perform reliably, will exhibit gradual degradation of performance, or will fail outright soon after implantation. Typically, the literature emphasizes the sensor that performed well, while only briefly (if at all) mentioning the failed devices. This leaves open the question of whether current sensor designs are adequate for the hostile in vivo environment, and whether these sensors have been assessed by the proper regimen of testing protocols. This paper reviews the current in vitro and in vivo testing procedures used to evaluate the functionality and biocompatibility of implantable glucose sensors. An overview of the standards and regulatory bodies that govern biomaterials and end product device testing precedes a discussion of up-to-date invasive and non-invasive technologies for diabetes management. Analysis of current in vitro, in vivo, and then post explantation testing is presented. Given the underlying assumption that the success of the sensor in vitro foreshadows the long-term reliability of the sensor in the human body, the relative merits of these testing methods are evaluated with respect to how representative they are of human models.
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