In vitro assessment of blood compatibility: residual and dynamic markers of cellular activation.
The blood compatibility of materials and surfaces used for medical device fabrication is a crucial factor in their function and effectiveness. Expansion of device use into more sensitive and longer term applications warrants increasingly detailed evaluations of blood compatibility that reach beyond the customary measures mandated by regulatory requirements. A panel of tests that assess both deposition on the surface and activation of circulating blood in contact with the surface has been developed. Specifically, the ability of a surface to modulate the biological response of blood is assessed by measuring: (1) dynamic thrombin generation; (2) surface-bound thrombin activity after exposure to blood; (3) activation of monocytes, polymorphonuclear leukocytes, lymphocytes, and platelets; (4) activation of complement; and (5) adherent monocytes, polymorphonuclear leukocytes, lymphocytes, and platelets on blood-contacting surfaces. The tests were used to evaluate surfaces modified with immobilized heparin (Ension's proprietary bioactive surface) and demonstrated that the modified surfaces reduced platelet activation, leukocyte activation, and complement activation in flowing human blood. Perfusion of the surfaces with human platelet-rich plasma showed that the immobilized heparin surfaces also reduce both dynamic thrombin levels in the circulating plasma and residual thrombin generated at the material surface.
Ension Inc., 240 William Pitt Way, Pittsburgh, Pennsylvania, PA 15238, USA. gjohnson@ension.com
Greg
G
Johnson
Benjamin
B
Curry
Linda
L
Cahalan
Roni
R
Prater
Michael
M
Beeler
Mark
M
Gartner
John
J
Biggerstaff
Patrick
P
Cahalan
D001672:Biocompatible Materials / Q000633:toxicity; D001773:Blood Cells / Q000187:drug effects / Q000502:physiology; D001790:Blood Physiological Phenomena / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D020099:Coated Materials, Biocompatible; D003167:Complement Activation / Q000187:drug effects; D006493:Heparin; D006801:Humans; D007962:Leukocytes / Q000187:drug effects / Q000502:physiology; D008422:Materials Testing / Q000295:instrumentation / Q000379:methods*; D015539:Platelet Activation / Q000187:drug effects; D013499:Surface Properties; D013917:Thrombin / Q000502:physiology
D001672:Biocompatible Materials; D020099:Coated Materials, Biocompatible; D006493:Heparin; D013917:Thrombin