University of Michigan

Accord Biomaterials, Inc.

Bong Kyun Oh

Mark E Meyerhoff

Melissa M Batchelor

Melissa M Reynolds

Biocompatible materials that have the ability to release nitric oxide (NO) in situ at the surface-blood interface when in contact with blood. The materials which may be polymers (e.g., polyurethane, poly(vinyl chloride), silicone rubbers), metals, such as stainless steel, carbon, and the like are provided with biocatalysts or biomimetic catalysts on their surface that have nitrite, nitrate, and/or nitrosothiol-reducing capability. Illustratively, the catalysts are adsorbed or immobilized at the surface of the material. The catalysts can act on endogenous nitrite, nitrate, or nitrosothiols within the blood creating a local increase in the NO levels at the surface of the material. An illustrative enzymatic biocatalyst is mammalian xanthine oxidase. In another illustrative embodiment, a biomimetic catalyst is a copper (Cu(II)-ligand complex, e.g. dibenzo[e,k]-2,3,8,9-tetraphenyl-1,4,7,10-tetraaza-cyclododeca-1,3,7,9-tetraene. In some cases, lipophilic salts of nitrite/nitrate (e.g., tridodecylmethylammonium nitrite (TDMANO/NO)) or certain salts of nitrosothiols can be doped within a polymer material, or an underlying polymeric film, to create a reservoir of nitrite or nitrosothiol that continuously leaks into the immobilized catalytic layer. Adequate levels of endogenous reducing equivalents are present within blood to provide catalytically-generated surface levels of NO that are above the threshold reportedly required to prevent platelet adhesion or activation.

Nitric oxide (NO) releasing material

A material includes a surface and a reactive agent that is located at the surface of the material, covalently attached to a backbone of the material, and/or located within the material. The reactive agent has nitrite reductase activity, nitrate reductase activity, and/or nitrosothiol reductase activity. The reactive agent also converts at least one of nitrites, nitrates and nitrosothiols to nitric oxide when in contact with blood. A reproducible nitrosothiol sensor is also disclosed.

Growing community of inventors

Ann Arbor, MI, United States of America

Bong Kyun Oh