Ions of structure X[N(O)NO]- display broad-spectrum pharmacological activity that correlates with the rate and extent of their spontaneous, first-order decomposition to nitric oxide when dissolved. We report incorporation of this functional group into polymeric matrices that can be used for altering the time course of nitric oxide release and/or targeting it to tissues with which the polymers are in physical contact. Structural types prepared include those in which the [N(O)NO]- group is attached to heteroatoms in low molecular weight species that are noncovalently distributed throughout the polymeric matrix, in groupings pendant to the polymer backbone, and in the polymer backbone itself. They range in physical form from films that can be coated onto other surfaces to microspheres, gels, powders, and moldable resins. Chemiluminescence measurements confirm that polymers to which the [N(O)NO]- group is attached can serve as localized sources of nitric oxide, with one prototype providing sustained NO release for 5 weeks in pH 7.4 buffer at 37 degrees C. The latter composition, a cross-linked poly-(ethylenimine) that had been exposed to NO, inhibited the in vitro proliferation of rat aorta smooth muscle cells when added as a powder to the culture medium and showed potent antiplatelet activity when coated on a normally thrombogenic vascular graft situated in an arteriovenous shunt in a baboon's circulatory system. The results suggest that polymers containing the [N(O)NO]- functional group may hold considerable promise for a variety of biomedical applications in which local delivery of NO is desired.

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Microelectromechanical systems (MEMS) create an opportunity for the development of smaller, cheaper, and more precise biomedical instrumentation and devices. Little is known, however, about the hemocompatibility of the materials used to fabricate these devices. Because of the potentially harmful consequences of thrombus formation, a better understanding of blood interactions with bioMEMS materials is desirable. This study is an in vitro assessment of the hemocompatibility of silicon (Si), silicon dioxide (SiO2), silicon nitride (Si3N4), low-stress silicon nitride (Si(1.0)N(1.1)), SU-8 photoresist, and parylene thin films. A polycarbonate-based polyurethane, was used as a reference material. Experiments were carried out to detect differences in platelet adhesion or morphology after contact with these materials under static conditions. Platelet adhesion on Si, Si3N4, Si(1.0)N(1.1,) and SU-8 photoresist was significantly greater (P < 0.05) than platelet adhesion on polyurethane. Adhesion on parylene and SiO(2) was not significantly different from on polyurethane (P < 0.05). The median platelet area and circularity were higher on polyurethane than all other materials. Materials that showed higher levels of platelet adhesion tended to have platelets that showed less spreading, except for SiO2, where platelets exhibited relatively low adhesion and spreading. This data suggests that Si, Si3N4, Si(1.0)N(1.1), and SU-8 photoresist may be more reactive to platelets and therefore more thrombogenic than parylene, SiO2, and polyurethane. These results may be helpful in guiding the selection of materials for use in the development of blood-contacting microelectromechanical systems.