title: Development and hemocompatibility testing of nitric oxide releasing polymers using a rabbit model of thrombogenicity.
abstract: Hemocompatibility is the goal for any biomaterial contained in extracorporeal life supporting medical devices. The hallmarks for hemocompatibility include nonthrombogenicity, platelet preservation, and maintained platelet function. Both in vitro and in vivo assays testing for compatibility of the blood/biomaterial interface have been used over the last several decades to ascertain if the biomaterial used in medical tubing and devices will require systemic anticoagulation for viability. Over the last 50 years systemic anticoagulation with heparin has been the gold standard in maintaining effective extracorporeal life supporting. However, the biomaterial that maintains effective ECLS without the use of any systemic anticoagulant has remained elusive. In this review, the in vivo 4-h rabbit thrombogenicity model genesis will be described with emphasis on biomaterials that may require no systemic anticoagulation for extracorporeal life supporting longevity. These novel biomaterials may improve extracorporeal circulation hemocompatibility by preserving near resting physiology of the major blood components, the platelets and monocytes. The rabbit extracorporeal circulation model provides a complete assessment of biomaterial interactions with the intrinsic coagulation players, the circulating platelet and monocytes. This total picture of blood/biomaterial interaction suggests that this rabbit thrombogenicity model could provide a standardization for biomaterial hemocompatibility testing.
authors.affiliation: Department of Surgery, University of Michigan Health System, Ann Arbor, USA tcmajor@umich.edu.
authors.forename: Terry C
authors.initials: TC
authors.lastname: Major
authors.affiliation: Department of Surgery, University of Michigan Health System, Ann Arbor, USA.
authors.forename: Hitesh
authors.initials: H
authors.lastname: Handa
authors.affiliation: Department of Pediatrics, University of Michigan Health System, Ann Arbor, USA.
authors.forename: Gail M
authors.initials: GM
authors.lastname: Annich
authors.affiliation: Department of Surgery, University of Michigan Health System, Ann Arbor, USA.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Bartlett
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000008:administration & dosage; D001672:Biocompatible Materials / Q000737:chemistry; D020099:Coated Materials, Biocompatible / Q000737:chemistry; D003692:Delayed-Action Preparations; D005112:Extracorporeal Circulation / Q000009:adverse effects*; D006487:Hemostasis; D008422:Materials Testing; D023421:Models, Animal; D020030:Nitric Oxide Donors / Q000008:administration & dosage*; D015539:Platelet Activation; D011108:Polymers / Q000737:chemistry; D011817:Rabbits; D013927:Thrombosis / Q000097:blood / Q000517:prevention & control*
chemical_list: D000925:Anticoagulants; D001672:Biocompatible Materials; D020099:Coated Materials, Biocompatible; D003692:Delayed-Action Preparations; D020030:Nitric Oxide Donors; D011108:Polymers
keywords: Hemocompatibilty; cGMP/P-VASP pathway; extracorporeal life support; monocytes; platelets; rabbit thrombogenicity model; thrombosis