Office of Technology Transfer – University of Michigan

Polyurethanes Doped with S-Nitrosothiols for Nitric Oxide Release

Technology #5584

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Researchers
Mark E. Meyerhoff
Managed By
Tiefei Dong
Senior Licensing Specialist, Life Sciences 734-763-5332
Patent Protection
US Patent Pending
US Patent Pending

This is a medical device coating polymer that incorporates nitric oxide (NO) donors that release NO into surrounding media and prevent thrombosis and platelet adhesion to the device, as well as biofilm formation. In healthy vasculature, endothelial cells generate NO to prevent thrombosis and platelet activation, but introduction of a foreign object disrupts vascular homeostasis and leads to severe complications. As advancements in medical technology are made and more people suffer from chronic diseases, there is a need for medical device coatings that will improve performance, reduce complications, and increase the life-span of these devices. Although NO-releasing materials can improve hemocompatibility, their tendency to leach NO donors in solution and instability during storage impose significant limitations to their use in biomedical applications. Improvements in their physical properties can greatly enhance their therapeutic potential.

SNAP-doped polymer is stable and inhibits platelet adhesion and thrombosis

Researchers in the Department of Chemistry at the University of Michigan developed an NO-releasing polymer with increased NO release time and shelf-life. S-nitrosothiols were incorporated into a hydrophobic polymer, and the rate of NO release into solution was measured. Biologically useful amounts of NO were released for up to three days of soaking in buffer at 37oC. The rate of NO release could be also be controlled by irradiation with 340 or 590 nm light. Over a 20 day period of soaking, about ¾ of the total NO released came from S-nitroso-N-acetylpenicillamine (SNAP) that remained in the polymer, indicating a low level of NO-donor diffusion and an increase in release lifetime. Addition of a top coat containing just the polymer slows down the rate of SNAP diffusion. Evaluation of NO releasing capacity of SNAP-doped polymer stored dry for two months at 37oC showed only a 20% loss of SNAP species. Finally, in an animal model for extracorporeal circulation (ECC), the SNAP-doped polymer coating reduced platelet adhesion to the ECC circuits and decreased the thrombus area. This coating technology provides a simple way to locally deliver NO and improve hemocompatibility of blood-contacting medical devices.

Applications

  • Improvement of hemocompatibility of medical devices
  • Prevention of platelet adhesion and thrombosis associated with devices
  • Prevention of infection and biofilm formation
  • Use in vascular grafts, stents, implantable catheters, ECCs

Advantages

  • Less NO donor leaching from polymer
  • Increase in NO release duration
  • Significantly improved stability and shelf-life
  • Photochemical and thermal trigger for NO release