Evaluations of diaminoalkane mediated immobilized heparin.

This dissertation entails the immobilization of heparin to polymer substrates and the characterization of the resultant heparin immobilized surfaces. To prevent crosslinking, all derivatization and immobilization reactions were conducted with N-acetylated heparin. Preliminary heparin derivatization studies demonstrated that carboxylic groups could be utilized in the covalent immobilization reactions if the number of participating carboxylic groups was minimized. It was found that the anticoagulant activity of the immobilized heparin increased with increasing spacer group length separating the immobilized heparin from the polymer surface. X-ray photoelectron spectroscopy revealed that the immobilized heparin was not associated with the surfaces of adsorbed protein layers following contact with protein solutions or plasma. These results suggested that the immobilized heparin was masked from platelets and unable to directly interact with platelets as is the case with soluble heparin. This hypothesis was substantiated by platelet retention and degranulation studies.