Covalently-bound heparin makes collagen thromboresistant.
OBJECTIVE
Blood compatibility of artificial surfaces depends on their immunogenic and thrombogenic properties. Collagen's weak antigenicity makes it an attractive candidate for stent coatings or fabrication of vascular grafts. However, the thrombogenic nature of collagen limits its application. We examined whether heparinization can make collagen more thromboresistant.


RESULTS
Collagen was heparinized by crosslinking collagen with extensively periodate oxidized heparin and/or by covalently bonding of mildly periodate oxidized heparin. Both ways of heparinization have no effect on platelet adhesion and could not abolish induction of platelet procoagulant activity. However, thrombin generation was completely prevented under static and flow conditions. The functionality of immobilized heparin was confirmed by specific uptake of antithrombin, 13.5+/-4.7 pmol/cm2 and 1.95+/-0.21 pmol/cm2 for mildly and heavily periodated heparin, respectively.


CONCLUSIONS
These results indicate that immobilization of heparin on collagen, even as a crosslinker, is a very effective way to prevent surface thrombus formation. These data encourage the application of heparinized collagen as stent-graft material in animal and eventually human studies.
Keuren
Jeffrey F W
JF
Department of Biochemistry, Maastricht University, Maastricht, The Netherlands.
Wielders
Simone J H
SJ
Driessen
Anita
A
Verhoeven
Michel
M
Hendriks
Marc
M
Lindhout
Theo
T
D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D000991:Antithrombins / Q000378:metabolism; D001777:Blood Coagulation / Q000187:drug effects; D001779:Blood Coagulation Factors / Q000378:metabolism; D002417:Cattle; D020099:Coated Materials, Biocompatible; D024042:Collagen Type I / Q000737:chemistry / Q000187:drug effects* / Q000494:pharmacology; D003432:Cross-Linking Reagents / Q000494:pharmacology*; D018056:Hemorheology; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D007113:Immunity, Innate; D016877:Oxidants / Q000494:pharmacology; D010084:Oxidation-Reduction; D010504:Periodic Acid / Q000494:pharmacology; D015539:Platelet Activation / Q000187:drug effects; D010973:Platelet Adhesiveness / Q000187:drug effects; D011485:Protein Binding; D025941:Protein Interaction Mapping; D013499:Surface Properties; D013917:Thrombin / Q000096:biosynthesis; D013927:Thrombosis / Q000517:prevention & control*
D017304:Annexin A5; D000991:Antithrombins; D001779:Blood Coagulation Factors; D020099:Coated Materials, Biocompatible; D024042:Collagen Type I; D003432:Cross-Linking Reagents; D016877:Oxidants; C049426:platelet procoagulant factor; D010504:Periodic Acid; D006493:Heparin; C009288:metaperiodate; D013917:Thrombin