TY - JOUR

T1 - Reversible hemostatic properties of sulfabetaine/quaternary ammonium modified hyperbranched polyglycerol

AU - Wen, Jiying

AU - Weinhart, Marie

AU - Lai, Benjamin

AU - Kizhakkedathu, Jayachandran

AU - Brooks, Donald E.

N1 - Funding Information: This research is supported by Natural Sciences and Engineering Council of Canada (NSERC) ( RPGIN 238852-11 ) and the Canadian Blood Services ( 201209-293 ). JNK is a recipient of a Michael Smith Foundation for Health Research Career Scholar Award. MW is grateful to the German Research Foundation ( WE 5377/1-1 ) (DFG) for financial support. Publisher Copyright: © 2016 Elsevier Ltd.

PY - 2016/4/1

Y1 - 2016/4/1

N2 - A library of hyperbranched polyglycerols (HPGs) functionalized with different mole fractions of zwitterionic sulfabetaine and cationic quaternary ammonium ligands was synthesized and characterized. A post-polymerization method was employed that utilized double bond moieties on the dendritic HPG for the coupling of thiol-terminated ligands via UV initiated thiol-ene "click" chemistry. The proportions of different ligands were precisely controlled by varying the ligand concentration during the irradiation process. The effect of the polymer library on hemostasis was investigated using whole human blood. It was found that polymer with ≥40% of alkenes converted to positive charges and the remainder to sulfabetaines caused hemagglutination at ≥1 mg/mL, without causing red blood cell lysis. The quaternary ammonium groups can interact with the negative charged sites on the membranes of erythrocytes, which provides the bioadhesion. The zwitterionic sulfabetaine evidently provides a hydration layer to partially mask the adverse effects that are likely to be caused by cationic moieties. The polymer was also found able to enhance platelet aggregation and activation in a concentration and positive charge density-dependent manner, which would contribute to initiating hemostasis. In a variety of other assays the material was found to be largely biocompatible. The polymer-induced hemostasis is obtained by a process independent of the normal blood clotting 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.

AB - A library of hyperbranched polyglycerols (HPGs) functionalized with different mole fractions of zwitterionic sulfabetaine and cationic quaternary ammonium ligands was synthesized and characterized. A post-polymerization method was employed that utilized double bond moieties on the dendritic HPG for the coupling of thiol-terminated ligands via UV initiated thiol-ene "click" chemistry. The proportions of different ligands were precisely controlled by varying the ligand concentration during the irradiation process. The effect of the polymer library on hemostasis was investigated using whole human blood. It was found that polymer with ≥40% of alkenes converted to positive charges and the remainder to sulfabetaines caused hemagglutination at ≥1 mg/mL, without causing red blood cell lysis. The quaternary ammonium groups can interact with the negative charged sites on the membranes of erythrocytes, which provides the bioadhesion. The zwitterionic sulfabetaine evidently provides a hydration layer to partially mask the adverse effects that are likely to be caused by cationic moieties. The polymer was also found able to enhance platelet aggregation and activation in a concentration and positive charge density-dependent manner, which would contribute to initiating hemostasis. In a variety of other assays the material was found to be largely biocompatible. The polymer-induced hemostasis is obtained by a process independent of the normal blood clotting 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.

KW - Betaines

KW - Bioadhesion

KW - Hemostasis

KW - Hyperbranched polyglycerol

KW - Polycations

UR - http://www.scopus.com/inward/record.url?scp=84975757453&partnerID=8YFLogxK

U2 - 10.1016/j.biomaterials.2016.01.067

DO - 10.1016/j.biomaterials.2016.01.067

M3 - Article

C2 - 26885776

AN - SCOPUS:84975757453

VL - 86

SP - 42

EP - 55

JO - Biomaterials

JF - Biomaterials

SN - 0142-9612

ER -