Novel Nitric Oxide (NO)-Releasing Polymers and their Biomedical Applications.

[摘要] Two common factors that can cause complications with indwelling biomedical devices are thrombus and infection.Nitric oxide (NO) is known to be a potent inhibitor of platelet activation and an antimicrobial agent.In this dissertation work, two novel approaches to achieving long-term NO release from polymers were studied and evaluated for their potential biomedical applications.First, S-nitroso-N-acetypenicillamine (SNAP)-doped Elast-eon E2As creates an inexpensive polymer that can locally deliver physiologically relevant levels of NO.SNAP was found to be stable in E2As during shelf-life stability and ethylene oxide sterilization studies.The SNAP/E2As polymer was coated on the inner walls of extracorporeal circulation (ECC) circuits and was found to preserve the platelet count at ~100% of baseline and reduce thrombus area after 4 h blood flow in a rabbit model.The SNAP/E2As polymer was also used to fabricate NO-releasing catheters that were implanted in sheep veins for 7 d.The SNAP/E2As catheters significantly reduced the amount of thrombus and bacterial adhesion. In the second approach, the NO release from diazeniumdiolated dibutylhexanediamine (DBHD/N2O2)-doped polymers was significantly improved using poly(lactic-co-glycolic acid) (PLGA) additives.Acid-capped PLGA additives were found to cause high initial bursts of NO, while ester-capped PLGA additives extended the NO release for up to 14 d.Poly(vinyl chloride)- and Elast-eon E2As were used as the base polymers for combined DBHD/N2O2 and PLGA coatings on the inner walls of ECC circuits.After 4 h of blood flow, the E2As-based NOrel circuits preserved platelets at a higher level than PVC-based NOrel circuits (97% and 80% of baseline, respectively).This demonstrates that the inherent hemocompatibility properties of the base polymer can also influence the efficiency of the NO release coatings.A DBHD/N2O2-doped SG-80A polymer material was also studied and used to fabricate patches that were applied to scald burn wounds infected with Acinetobacter baumannii.The NO released from these patches applied to the wounds is shown to significantly reduce the A. baumannii infection after 24 h.The results for both of types of NO-releasing polymers studied here demonstrated greatly enhanced hemocompatibility properties that can be applied to a wide variety of blood-contacting medical devices.

[发布机构] University of Michigan

[效力级别] S-nitrosothiol

[关键词] Nitric Oxide;S-nitrosothiol;Hemocompatibility;Biocompatibility;Chemistry;Science;Chemistry