Nitric oxide-releasing polyurethane membranes for implantable electrochemical glucose sensors

The development of novel biocompatible membranes is key to mitigating the host foreign body response (FBR) that limits the utility of implantable electrochemical biosensors for continuous glucose monitoring. Nitric oxide (NO)---an endogenously produced physiological mediator involved in wound healing, angiogenesis, and the inflammatory response---has been shown to reduce the FBR and may enhance sensor utility when released from sensor membranes.;Nitric oxide-releasing glucose sensor membranes with tunable release kinetics and total payloads were fabricated utilizing polyurethane (PU) films doped with NO donor-modified silica nanoparticles. A wide range of NO-release fluxes (5-460 pmol cm-2 s-1) and durations (16 h to 14 d) were achieved by altering the type of dopant, as well as the PU sensor membrane composition and concentration. Sensor performance was affected by water uptake and membrane thickness regardless of the type of NO-release vehicle.;To combine the potential benefits of both NO-release and porous scaffolds in one engineered material, NO-releasing fibrous PU membranes were fabricated via electrospinning. Electrospun PU fibers doped with NO-releasing silica particles exhibited a wide range of NO-release totals and durations (7.5-120 nmol mg-1 and 7 h to 14 d, respectively). These materials exhibited ~83% porosity with flexible plastic or elastomeric behavior, and a wide range of fiber diameters (119--614 nm) and mechanical strength (moduli of 1.7--34.5 MPa).;Nitric oxide-releasing electrospun fibers were applied to needle-type glucose sensors as the outermost membrane. The NO-releasing dendrimer-doped PU fiber mats maintained their porosity in serum without dendrimer leaching. Sensor performance was not significantly impacted by the additional porous membrane (≤50 microm thickness). The glucose sensitivity was 2.4 +/- 1.6 nA/mM with a dynamic range 1--24 mM, indicating clinically acceptable performance.;In vivo analytical sensor performance was assessed using NO-releasing membrane-modified glucose biosensors in a porcine model. The NO-releasing sensors were shown to continuously monitor glucose for one week with 91.8% of determinations indicated as clinically accurate and acceptable. This research illustrated the ability to create functional NO-releasing glucose sensors so future studies can focus on thoroughly evaluating the benefits of NO release and porosity on in vivo analytical performance.