Development of nitric oxide -releasing polymers with improved blood compatibility.
Zhang, Huiping
2002
Abstract
To devise more biocompatible materials for use in blood contacting devices, nitric oxide (NO)-releasing polymers have been designed to mimic non-thrombogenic endothelial cells (EC), which continuously release NO<sub> (g)</sub> to inhibit platelet activation on the inner surfaces of blood vessels. This dissertation describes the synthesis/formulation, characterization, and <italic> in vivo</italic> evaluation of various NO-releasing polymers, including silicone rubber (SR), polyurethane (PU), and poly(vinyl chloride) (PVC). Nitric oxide-releasing SR was synthesized via a two-step reaction scheme. A diamine-containing SR crosslinking agent (<italic>N</italic>-(6-aminohexyl)-3-aminopropyl-trimethoxysilane, DACA-6) was employed to introduce diamine sites into the moisture-cured SR matrix. These diamine groups were then converted to <italic>N</italic>-diazeniumdiolate groups, when the cured SR films were reacted with NO<sub>(g)</sub> at elevated pressure (80 psi) in the presence of sodium methoxide (NaOMe). <italic>N</italic>-Diazeniumdiolate groups were also formed during the NO-addition reaction in the absence of NaOMe; however, <italic>N</italic>-nitrosamine was found to form as the major product. The <italic>N</italic>-diazeniumdiolate moieties formed within the SR matrices could dissociate into NO<sub>(g)</sub> via both proton-driven and thermal pathways. Nitric oxide-releasing PU and PVC were formulated by the incorporation of <italic>N</italic>-diazeniumdiolate-functionalized fumed silica particles within the polymer matrices. Such NO-releasing silica particles were synthesized by first tethering amine groups onto silica surface using amine-containing silylation reagents (e.g., DACA-6). These amine groups were then converted to corresponding <italic>N</italic>-diazeniumdiolate groups via reaction with NO<sub>(g)</sub> at high pressure in the presence of methoxide bases (e.g., NaOMe). The <italic>N</italic>-diazeniumdiolate groups were found to undergo a primarily proton-driven dissociation to NO<sub>(g)</sub> under physiological conditions, with apparent reaction order greater than 1. The rates of <italic> N</italic>-diazeniumdiolate dissociation were related to the parent amine structures and the pH of the soaking buffer. These NO-releasing polymers exhibited enhanced thromboresistivity during extracorporeal circulation (ECC) experiments on a rabbit model via release of NO<sub>(g)</sub> at levels equal to or higher than that from stimulated EC (4.1 x 10<super>-10</super> mole/cm<super>2</super>/min). In addition to ECC applications, the NO-releasing SR was also used to fabricate fluorescent oxygen sensing films to explore its potential application in intravascular sensors. The work described herein clearly demonstrates the great potential of the NO-release strategy toward the development of more blood compatible polymers.Subjects
Blood Compatibility Development Improved Nitric Oxide-releasing Polymers
Types
Thesis
Metadata
Show full item recordCollections
Remediation of Harmful Language
The University of Michigan Library aims to describe library materials in a way that respects the people and communities who create, use, and are represented in our collections. Report harmful or offensive language in catalog records, finding aids, or elsewhere in our collections anonymously through our metadata feedback form. More information at Remediation of Harmful Language.
Accessibility
If you are unable to use this file in its current format, please select the Contact Us link and we can modify it to make it more accessible to you.