title: Macrophage embedded fibrin gels: an in vitro platform for assessing inflammation effects on implantable glucose sensors.
abstract: The erroneous and unpredictable behavior of percutaneous glucose sensors just days following implantation has limited their clinical utility for diabetes management. Recent research has implicated the presence of adherent inflammatory cells as the key mitigating factor limiting sensor functionality in this period of days post-implantation. Here we present a novel in vitro platform to mimic the cell-embedded provisional matrix that forms adjacent to the sensor immediately after implantation for the focused investigation of the effects of early stage tissue response on sensor function. This biomimetic surrogate is formed by imbibing fibrin-based gels with physiological densities of inflammatory RAW 264.7 macrophages. When surrounding functional sensors, macrophage-embedded fibrin gels contribute to sensor signal declines that are similar in both shape and magnitude to those observed in previous whole blood and small animal studies. Signal decline in the presence of gels is both metabolically-mediated and sensitive to cell type and activation. Computational modeling of the experimental setup is also presented to validate the design by showing that the cellular glucose uptake parameters necessary to achieve such experimental declines align well with literature values. Together, these data suggest this in vitro provisional matrix surrogate may serve as an effective screening tool for testing the biocompatibility of future glucose sensor designs.
authors.affiliation: Department of Biomedical Engineering, Duke University, 136 Hudson Hall, Box 90281, Durham, NC 27708, USA.
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Novak
authors.affiliation: Department of Biomedical Engineering, Duke University, 136 Hudson Hall, Box 90281, Durham, NC 27708, USA.
authors.forename: Fan
authors.initials: F
authors.lastname: Yuan
authors.affiliation: Department of Biomedical Engineering, Duke University, 136 Hudson Hall, Box 90281, Durham, NC 27708, USA. Electronic address: reichert@duke.edu.
authors.forename: William M
authors.initials: WM
authors.lastname: Reichert
mesh_terms: D016475:3T3 Cells; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D015374:Biosensing Techniques / Q000295:instrumentation; D001786:Blood Glucose / Q000032:analysis*; D002460:Cell Line; D018914:Cells, Immobilized / Q000166:cytology / Q000276:immunology; D005337:Fibrin / Q000737:chemistry*; D005782:Gels / Q000737:chemistry*; D007249:Inflammation / Q000209:etiology* / Q000276:immunology; D008264:Macrophages / Q000166:cytology / Q000276:immunology*; D051379:Mice; D019736:Prostheses and Implants / Q000009:adverse effects*
chemical_list: D001672:Biocompatible Materials; D001786:Blood Glucose; D005782:Gels; D005337:Fibrin
keywords: Biocompatibility; Biosensors; Immune response; Inflammation; Macrophage