Hemocompatibility studies on a degradable polar hydrophobic ionic polyurethane (D-PHI).
Biomaterial blood compatibility is a complex process that involves four key pathways, including the coagulation cascade, the complement system, platelets, and leukocytes. While many studies have addressed the initial contact of blood with homopolymeric (e.g. Teflon) or simple copolymeric (e.g. Dacron) biomaterials, relatively less attention has been given to investigating blood coagulation with respect to complex copolymeric systems containing well defined and diverse function. The current study sought to assess the hemocompatibility of a complex polyurethane (PU) containing a unique combination of polar, hydrophobic, and ionic domains (D-PHI). This included a whole blood (WB) study, followed by tests on the intrinsic and extrinsic coagulation pathways, complement activation, platelet activation, and an assessment of the effect of leukocytes on platelet-biomaterial interactions. A small increase in blood clot formation was observed on D-PHI in WB; however, there was no significant increase in clotting via the intrinsic coagulation cascade. No significant increase in platelet adhesion and only a very slight increase in platelet activation were observed in comparison to albumin-coated substrates (negative control). D-PHI showed mild complement activation and increased initiation of the extrinsic pathway of coagulation, along with the observation that leukocytes were important in mediating platelet-biomaterial interactions. It is proposed that complement is responsible for activating coagulation by inciting leukocytes to generate tissue factor (TF), which causes extrinsic pathway activation. This low level of blood clotting on D-PHI's surface may be necessary for the beneficial wound healing of vascular constructs that has been previously reported for this material.



Understanding the hemocompatibility of devices intended for blood-contacting applications is important for predicting device failure. Hemocompatibility is a complex parameter (affected by at least four different mechanisms) that measures the level of thrombus generation and immune system activation resulting from blood-biomaterial contact. The complexity of hemocompatibility implies that homopolymers are unlikely to solve the clotting challenges that face most biomaterials. Diversity in surface chemistry (containing hydrophobic, ionic, and polar domains) obtained from engineered polyurethanes can lead to favourable interactions with blood. The current research considered the effect of a highly functionalized polyurethane biomaterial on all four mechanisms in order to provide a comprehensive in vitro measure of the hemocompatibility of this unique material and the important mechanisms at play.
Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, Ontario M5S 3R5, Canada; Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario M5S 3G9, Canada.
Kathryne S
KS
Brockman
Department of Pathology and Laboratory Medicine and Centre for Blood Research, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada; Department of Chemistry, University of British Columbia, Vancouver, British Columbia V6T 1Z1, Canada.
Jayachandran N
JN
Kizhakkedathu
Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, Ontario M5S 3R5, Canada; Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario M5S 3G9, Canada; Faculty of Dentistry, University of Toronto, Toronto, Ontario M5G 1G6, Canada. Electronic address: paul.santerre@dentistry.utoronto.ca.
J Paul
JP
Santerre
D000818:Animals; D001672:Biocompatible Materials / Q000494:pharmacology*; D001777:Blood Coagulation / Q000187:drug effects; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D003167:Complement Activation / Q000187:drug effects; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007477:Ions; D008422:Materials Testing / Q000379:methods*; D010314:Partial Thromboplastin Time; D010973:Platelet Adhesiveness / Q000187:drug effects; D011140:Polyurethanes / Q000737:chemistry*; D011517:Prothrombin Time; D012756:Sheep; D013916:Thrombelastography
D001672:Biocompatible Materials; D007477:Ions; D011140:Polyurethanes
Biomaterials; Complement activation; Leukocytes; Platelets; Polyurethane; Thrombosis