Nitric oxide (NO)-releasing sol-gel materials are synthesized by combining aminefunctionalized alkoxysilanes (aminosilanes) with alkyltrimethoxysilanes (alkylsilanes). Upon hydrolysis and condensation, the amine-functionalized silanes are covalently bound to the alkyltrimethoxysilane backbone and easily converted to diazeniumdiolate NO donors via exposure to high pressures of NO. Immersion of the sol-gel into solution is not required to initiate NO release. The NO-release characteristics of the sol-gels are easily controlled by varying the type and amount of the aminosilane precursor in the sol. The sol-gel coatings release NO for up to 20 d with average fluxes between 8.0 × 10 -12 and 5.6 × 10 -11 mol‚s -1 ‚cm -2 (coating thickness of 50 µm) over the first 10 h. These materials exhibit reduced platelet and bacterial adhesion. The results indicate that sol-gel chemistry may be an effective strategy for preparing coatings that release NO both controllably and locally for a range of applications including blood-and tissue-based devices.

Thirty years ago, there was an emerging appreciation for the significance of oxidative stress in newborn disease. This prompted a renewed interest in the impact of oxygen therapy for the newborn in the delivery room and beyond, especially in premature infants. Today, the complexity of oxidative stress both in normal regulation and pathology is better understood, especially as it relates to neonatal mitochondrial oxidative stress responses to hyperoxia. Mitochondria are recipients of oxidative damage and have a propensity for oxidative self-injury that has been implicated in the pathogenesis of neonatal lung diseases. Similarly, both intrauterine growth restriction (IUGR) and macrosomia are associated with mitochondrial dysfunction and oxidative stress. Additionally, reoxygenation with 100% O2 in a hypoxic-ischemic newborn lamb model increased the production of pro-inflammatory cytokines in the brain. Moreover, the interplay between inflammation and oxidative stress in the newborn is better understood because of animal studies. Transcriptomic analyses have found a number of genes to be differentially expressed in murine models of bronchopulmonary dysplasia (BPD). Epigenetic changes have also been detected both in animal models of BPD and premature infants exposed to oxygen. Antioxidant therapy to prevent newborn disease has not been very successful; however, new therapeutic principles, like melatonin, are under investigation.

Diazeniumdiolate-modified sol-gel microarrays capable of releasing low levels of nitric oxide are reported as a viable means for improving the blood compatibility of a surface without fully modifying the underlying substrate. Several parameters are characterized including: (1) NO surface flux as a function of sol-gel composition and microarray geometry; (2) microstructure dimensions and spacing for optimal blood compatibility; and (3) the effect of sol-gel surface modification on analyte accessibility to platinum electrodes. The sol-gel microarrays release biologically relevant levels of NO under physiological conditions for >24 h. In vitro platelet adhesion assays indicate that a NO surface flux of 2.2 pmol cm(-2) s(-1) effectively reduces platelet adhesion to glass substrates modified with sol-gel microstructures separated by 50 microm. The blood compatibility observed for these micropatterned surfaces is comparable to NO-releasing sol-gel films. When the separation between NO-releasing microstructures is reduced to 10 microm, the NO surface flux required to reduce platelet adhesion is lowered to 0.4 pmol cm(-2) s(-1). Finally, the oxygen response of platinum electrodes modified with NO-releasing sol-gel microarrays indicates that selective modification via micropatterning enhances analyte accessibility to the sensor surface.

The release of nitric oxide (NO) from polymers has proven to be highly effective at inhibiting platelet adhesion and thus enhancing the blood compatibility of medical implants. Micropatterning techniques were used to design surfaces that release NO while preserving the underlying substrate for other applications (e.g., sensors). Micropatterned NO-releasing substrates based on aminosilane-containing methyltrimethoxysilane sol-gels were prepared and characterized in terms of stability, NO surface flux, and resistance to in vitro platelet adhesion. We have found that surface-localized NO release from substrates modified with sol-gel micropatterns exhibit enhanced blood compatibility relative to controls.