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 (ECLS) 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 ECLS. 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 ECLS longevity. These novel biomaterials may improve extracorporeal circulation (ECC) hemocompatibility by preserving near resting physiology of the major blood components, the platelets and monocytes. The rabbit ECC 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.

Recent advances in thromboresistant and antimicrobial polymers for biomedical applications: just say yes to nitric oxide (NO)

“…The need for systemic anticoagulation in each of these extracorporeal procedures can be problematic, particularly in patients that have heparin induced thrombocytopenia (HIT). Due to the large surfaces area that is in contact with blood in extracorporeal circulation (ECC), the loss of platelet count and platelet functionality are significant, 161 and many researchers have developed NO releasing 43,154,155,161,236,238,278,279 or NO generating 254 polymeric ECC tubing to prevent platelet activation and consumption during this process (see Table 1). …”

Characterization and in vivo performance of nitric oxide‐releasing extracorporeal circuits in a feline model of thrombogenicity

“…Researchers have developed NO‐releasing materials as a way to increase hemocompatibility of blood contacting devices such as vascular grafts, stents, intravascular catheters, and extracorporeal life support circuits . One method to improve the hemocompatibility of these existing materials is through the use of coatings, where the coating can more closely mimic the natural NO release from the endothelium …”

“…Ex vivo clot formation provides a mechanism to study the characteristics of thrombus formation, and may also be useful for the assessment of the efficacy of antithrombotic medications. The use of a flexible plastic extracorporeal circuit (ECC) has been reported in a rabbit model of thrombogenicity . The circuit connects the carotid artery to the contralateral external jugular vein to provide flow without the use of roller pumps or other mechanical assistance.…”

“…As described previously, the surface of the ECC tubing can be coated with polymers that can minimize the blood/biomaterial interaction, and decrease the thrombogenicity of the ECC . Improving the hemocompatibility of the ECC surface may be used for various extracorporeal therapies such as hemodialysis, extracorporeal membrane oxygenation (ECMO), and cardiopulmonary bypass.…”

The optimal incubation time for in vitro hemocompatibility testing: Assessment using polymer reference materials under pulsatile flow with physiological wall shear stress conditions

“…Improper hemocompatibility assessments may result in unjustly use of blood contacting medical devices that can lead to extensive inflammation and hemolysis, or even a direct risk for life‐threatening conditions as a result of the formation of blood clots, thrombi, and/or (micro)embolisms . Although the thrombogenicity of medical devices may be attenuated by the administration of platelet inhibitors and/or anticoagulants, higher doses are needed for hemo‐incompatible medical devices as compared to more hemocompatible medical devices …”