Nitric oxide inhibition of platelet deposition on biomaterials

Platelet adhesion and aggregation restrict the clinical applicability of blood-contacting biomaterials. Nitric oxide (NO) is a simple biological molecule that may be incorporated into biomaterials to inhibit platelet deposition. The toxicity of NO at superphysiological levels necessitates the determination of aqueous NO concentrations and fluxes that effectively inhibit platelet deposition. In this study, a novel NO delivery device has been developed to study NO inhibition of platelet deposition in a dynamic in vitro environment. Gaseous NO was delivered via a semipermeable membrane to a radiolabeled platelet suspension perfusing a thin flow slit. The membrane was coated with a platelet-agonistic protein. Spatial NO flux and concentration profiles in the flow slit are predictable using a mathematical model. Platelet inhibition was essentially complete at 0.1 ppm gaseous NO exposure, corresponding to a surface concentration of 0.09 nM and surface fluxes between 0.3 and 0.6 femtomoles cm-2s-1. These threshold values of NO exposure for significant platelet inhibition were unchanged irrespective of the platelet agonist, perfusion times, or shear rates. At lower NO exposures (0.02 ppm), platelet inhibition was only partial with the degree of inhibition dependent on the nature of the agonistic protein. This study yields information useful towards the design and development of biomaterials incorporating NO for the reduction of platelet-biomaterial interactions.