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Electrospun polyurethane-core and gelatin-shell coaxial fibre coatings for miniature implantable biosensors.

ABSTRACT: The aim of this study was to introduce bioactivity to the electrospun coating for implantable glucose biosensors. Coaxial fibre membranes having polyurethane as the core and gelatin as the shell were produced using a range of polyurethane concentrations (2, 4, 6 and 8% wt/v) while keeping gelatin concentration (10% wt/v) constant in 2,2,2-trifluoroethanol. The gelatin shell was stabilized using glutaraldehyde vapour. The formation of core-shell structure was confirmed using transmission/scanning electron microscopy and FTIR. The coaxial fibre membranes showed uniaxial tensile properties intermediate to that of the pure polyurethane and the gelatin fibre membranes. The gelatin shell increased hydrophilicity and glucose transport flux across the coaxial fibre membranes. The coaxial fibre membranes having small fibre diameter (541 nm) and a thick gelatin shell (52%) did not affect the sensor sensitivity, but decreased sensor's linearity in the long run. In contrast, thicker coaxial fibre membranes (1133 nm) having a thin gelatin shell (34%) maintained both sensitivity and linearity for the 84 days of the study period. To conclude, polyurethane-gelatin coaxial fibre membranes, due to their faster permeability to glucose, tailorable mechanical properties and bioactivity, are potential candidates for coatings to favourably modify the host responses to extend the reliable in vivo lifetime of implantable glucose biosensors.

SUBMITTER: Wang N

PROVIDER: S-EPMC3969240 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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Project description:Continuous glucose sensors offer the promise of tight glycemic control for insulin dependent diabetics; however, utilization of such systems has been hindered by issues of tissue compatibility. Here we report on the in vivo performance of implanted glucose sensors coated with Dexamethasone-loaded (Dex-loaded) porous coatings employed to mediate the tissue-sensor interface. Two animal studies were conducted to (1) characterize the tissue modifying effects of the porous Dex-loaded coatings deployed on sensor surrogate implants and (2) investigate the effects of the same coatings on the in vivo performance of Medtronic MiniMed SOF-SENSOR™ glucose sensors. The tissue response to implants was evaluated by quantifying macrophage infiltration, blood vessel formation, and collagen density around implants. Sensor function was assessed by measuring changes in sensor sensitivity and time lag, calculating the Mean Absolute Relative Difference (MARD) for each sensor treatment, and performing functional glucose challenge test at relevant time points. Implants treated with porous Dex-loaded coatings diminished inflammation and enhanced vascularization of the tissue surrounding the implants. Functional sensors with Dex-loaded porous coatings showed enhanced sensor sensitivity over a 21-day period when compared to controls. Enhanced sensor sensitivity was accompanied with an increase in sensor signal lag and MARD score. These results indicate that Dex-loaded porous coatings were able to elicit an attenuated tissue response, and that such tissue microenvironment could be conducive towards extending the performance window of glucose sensors in vivo.Statement of significanceIn the present article, a coating to extend the functionality of implantable glucose sensors in vivo was developed. Our study showed that the delivery of an anti-inflammatory agent with the presentation of micro-sized topographical cues from coatings may lead to improved long-term glucose sensor function in vivo. We believe that improved function of sensors treated with the novel coatings was a result of the observed decreases in inflammatory cell density and increases in vessel density of the tissue adjacent to the devices. Furthermore, extending the in vivo functionality of implantable glucose sensors may lead to greater adoption of these devices by diabetic patients.

Project description:In an effort to add to the versatility of three-dimensional scaffolds for tissue engineering applications, recent experimental designs are incorporating biological molecules such as plasmids and proteins within the scaffold structure. Such scaffolds act as reservoirs for the biological molecules of interest while regulating their release over various durations of time. Here, we describe the use of coaxial electrospinning as a means for the fabrication of fiber mesh scaffolds and the encapsulation and subsequent release of a non-viral gene delivery vector over a period of up to 60 days. Various fiber mesh scaffolds containing plasmid DNA (pDNA) within the core and the non-viral gene delivery vector poly(ethylenimine)-hyaluronic acid (PEI-HA) within the sheath of coaxial fibers were fabricated based on a fractional factorial design that investigated the effects of four processing parameters at two levels. Poly(epsilon-caprolactone) sheath polymer concentration, poly(ethylene glycol) core polymer molecular weight and concentration, and the concentration of pDNA were investigated for their effects on average fiber diameter, release kinetics of PEI-HA, and transfection efficiency. It was determined that increasing the values of each of the investigated parameters caused an increase in the average diameter of the fibers. The release kinetics of PEI-HA from the fibers were affected by the loading concentration of pDNA (with PEI-HA concentration adjusted accordingly to maintain a constant nitrogen to phosphorous (N:P) ratio within the complexes). Two-dimensional cell culture experiments with model fibroblast-like cells demonstrated that complexes of pDNA with PEI-HA released from fiber mesh scaffolds could successfully transfect cells and induce expression of enhanced green fluorescent protein (EGFP). Peak EGFP expression varied with the investigated processing parameters, and the average transfection observed was a function of poly(ethylene glycol) (core) molecular weight and concentration. Furthermore, fibroblast-like cells seeded directly onto coaxial fiber mesh scaffolds containing PEI-HA and pDNA showed EGFP expression over 60 days, which was significantly greater than the EGFP expression observed with scaffolds containing pDNA alone. Hence, variable transfection activity can be achieved over extended periods of time upon release of pDNA and non-viral gene delivery vectors from electrospun coaxial fiber mesh scaffolds, with release and subsequent transfection controlled by tunable coaxial fiber mesh fabrication parameters.

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Electrospun polyurethane-core and gelatin-shell coaxial fibre coatings for miniature implantable biosensors.

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