Date of Award
Doctor of Philosophy (PhD)
Polyurethanes have been a material of choice for the fabrication of many conventional blood-contact devices such as vascular grafts, cardiac assist devices and total artificial hearts. Although these applications have had some success for short term applications there is a major limitation in their use for long term applications. The deficiency of the current devices and their associated materials arises from the foreign nature of these prostheses with respect to the body. Most often these devices initiate a natural physiological response that defends the body by attacking the foreign surfaces. When the materials contact with blood, the response is a series of events which lead to the eventual formation of a thrombus. In turn this often results in the dislodging of microscopic thrombi which can embolize and cause strokes.
There is therefore a need to better understand the interactions of blood with polyurethanes and to develop polyurethanes of improved blood compatibility. In this thesis the proposition is explored that improved materials may be achieved by incorporating chemical functional groups that are known to be important in the interactions of vascular and other components tending to prevent thrombogenesis. These components are the plasma proteins, the blood cells and the endothelium. Thus functional groups have been incorporated covalently into "conventional" polyurethanes as follows: (1) sulfonate groups which are an important component of the vascular wall and of the anticoagulant heparin, (2) certain amino acid moieties which are involved in the neutralization of clotting enzymes particularly serine proteases, (3) hydrocarbon chains which might be expected to bind albumin, a passivating protein, from blood, and (4) polyethylene oxide chains which might be expected to simulate the hydrogel-like nature of quiescent blood cell/plasma interfaces and which have been shown by others to minimize interactions with proteins.
The novel polyurethane materials were extensively characterized for several aspects of bulk and surface properties and response to plasma proteins. The functionalized materials were found to have greatly modified properties relative to conventional non-functionalized polyurethanes. Using differential scanning calorimetry and Fourier transform infra-red spectroscopy it was possible to associate this modified behaviour with the formation of Ionic clusters within the microdomain structures of the polyurethanes.
The different functional groups of the sulfonated and derivatized polymers allow the materials to achieve very high levels of water uptake. These elevated water levels give a hydrogel-like character to the polymers which in turn yields very low contact angle values. Furthermore, it would appear from ESCA (electron spectroscopy for chemical analysis) surface analysis data and the time dependence of sessile drop contact angle data that the material surface in air is substantially different than when the surface is contacted with an aqueous medium.
Measurements of the adsorption of fibrinogen from plasma and buffer were carried out using radiolabelling methods. The specific functionality of the different materials combine with their hydrogel-like nature to yield fibrinogen adsorption patterns in plasma that are unique and different from previously studied polyurethanes. Some of the materials were evaluated for their ability to delay plasma clotting times using standard thrombin time measurements. The results would suggest that sulfonaed and some derivatized polyurethanes may be capable of deactivating thrombin, which is a key enzyme in the formation of fibrin, the primary constituent of blood clots.
The work of this thesis makes the following contributions: (i) a general method of introducing chemical function into the hard segment of polyurethanes involving reaction of amine or hydroxyl groups with sulfonyl chloride, (ii) improved understanding of polyurethane ionomer structure. (iii) methods of controlling protein interactions and water uptake of polyurethanes by incorporation of specific functional groups.
Santerre, Joseph Paul Patrice-Guy, "Sulfonated and Derivatized Sulfonated Polyurethanes for Biomedical Applications" (1990). Open Access Dissertations and Theses. Paper 3552.