New biomaterials for the sustained release of nitric oxide: past, present and future

Nitric oxide (NO), the 1992 'Molecule of the Year', is the focus of immense medical and scientific exploration. Interest in NO has grown exponentially since the initial and relatively recent discovery that NO is the long sought after endothelial relaxing factor. There is intense research that is continuing to expose the extensive physiologic impact of NO in virtually all organ and tissue systems under both normal and pathological conditions. Both the rate of delivery and the amount of site-specific generated NO modulate a balance between cytoregulatory and cytotoxic activities. This balancing act and the very short lifetime of NO under physiological conditions pose an extreme challenge with respect to harnessing the exceptional therapeutic potential of this molecule. Over the past two decades, the race to translate the therapeutic potential of NO to the bedside has been overwhelmingly through the development of numerous NO delivery devices/vehicles. So far no one product has emerged as a clearcut winner. This review: discusses and evaluates NO-donating platforms that are available at present; attempts to enhance delivery and efficacy through encapsulation in silane-based hydrogel matrices; and discusses and evaluates the future direction of these advances.