Nitric oxide-releasing xerogel microarrays for improving the biocompatibility of medical implants

A novel strategy for designing interfaces that are resistant to in vitro biofouling via controlled nitric oxide (NO) release and retain a high degree of functionality since only portions of the underlying surface are modified is described. Sol-gel chemistry affords tremendous flexibility in preparing thin (∼10 mum) aminosilane-modified xerogel surface coatings with tunable NO-release properties by varying the reaction processing conditions and/or xerogel precursors. Stable, optically transparent xerogels capable of releasing therapeutic levels of NO for up to 24 h were formed by copolymerizing methyltrimethoxysilane (MTMOS) with (aminoethylaminomethyl)phenethyl-trimethoxysilane (AEMP3) and exposing the cured polymer to NO (5 atm, 3d).; The low solution viscosity of AEMP3/MTMOS sols enabled selective substrate modification with NO-releasing xerogels via replica molding and capillary flow of the sol through poly(dimethysiloxane) (PDMS) microchannels. Micropatterning offered an additional parameter for modulating xerogel NO-release properties by varying microstructure geometry and dimensions. Arrays of xerogel lines separated by up to 50 mum were equally resistant to in vitro platelet adhesion as uniform xerogel coatings at a NO surface flux of 2.2 pmol·cm-2·s-1. At reduced microstructure separations (≤10 mum) a NO surface flux of only 0.4 pmol·cm-2·s-1 effectively inhibited platelet adhesion. Furthermore, the analytical response of micropatterned electrodes was significantly enhanced relative to comparable xerogel-coated sensors, due to increased analyte diffusion to the electrode surface between xerogel microstructures.; The sensitivity of a miniaturized enzyme-based glucose biosensor modified with a NO-releasing xerogel microarray was slightly reduced relative to the control sensor due to limited glucose diffusion. However, a rapid, linear, and stable (7d) response over the physiologically relevant glucose concentration range was achieved with micropatterned lines (width = 5 mum, height = 1.5 mum) separated by 20 mum. The NO-releasing micropatterned sensor exhibited improved in vitro biocompatibility with respect to both bacterial and platelet adhesion for ≥24 h.; To extend the therapeutic effects of NO-releasing micropatterned surfaces, ultraviolet polymer grafting was employed to increase the wettability of the PDMS template channels. This strategy proved effective for micropatterning a range of aminosilane-based sols with significantly enhanced NO release capabilities relative to AEMP3/MTMOS xerogels (i.e., ≥96 h).