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The chemical modification of hyperbranched polyglycerols for improved bioadhesive and hemostatic properties

University of British Columbia

Enhancement of hemostasis at the site of wound is a very attractive method to limit bleeding and to reduce the need for blood transfusion support. However, many commercially available bioadhesives and hemostatic agents fail to fulfill the design requirements of efficacy, safety and cost. There is a need to develop novel bioadhesive and hemostatic agents that would overcome these limitations. A library of hyperbranched polyglycerol (HPG) based macromolecular structures functionalized with different mole fractions of zwitterionic sulfabetaine and cationic quaternary ammonium ligands were synthesized and characterized. A post-polymerization method was employed that utilized double bond moieties on the HPG backbone for the coupling of thiolcapped functional groups via UV initiated thiol-ene “click” chemistry. The proportions of different ligands were precisely controlled by varying the monomer concentration during the irradiation process. The effect of the polymer on hemostasis has been investigated using whole blood. It was found that polymer with 40% or more positive charged groups caused hemagglutination without causing red blood cell lysis. The quaternary ammonium groups can interact with the negative charged sites on the membranes of erythrocytes, which improves the bioadhesiveness. The zwitterionic sulfabetaine can provide a hydration layer to partially mask the adverse effects that are likely to be caused by cationic moieties on the integrity of cell membrane. The conjugate was also found to be able to enhance platelet aggregation and activation in a concentration and positive charge density dependent manner, which would contribute to the initiation of hemostasis. The polymer-induced hemostasis is obtained by a process independent of the normal iii blood coagulation cascade but dependent on red blood cell agglutination, where the polymers promote hemostasis by linking erythrocytes together to form a lattice to entrap the cells.

Text

2016-08-31

Attribution-NonCommercial-NoDerivs 2.5 Canada

http://hdl.handle.net/2429/54657

Chemistry

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/2.5/ca/