Nonglutaraldehyde treated porcine pericardium with good biocompatibility, reduced calcification and improved Anti-coagulation for bioprosthetic heart valve applications

Abstract

Heart valve diseases, such as valve stenosis and regurgitation, are one of the important reasons for the high morbidity and mortality of cardiovascular diseases, and the heart valve replacement has become the optimal option for severe heart valve disease treatment. With the development of transcatheter heart valve replacement technology and aging population, the usage of bioprosthetic heart valves (BHVs) has been largely expanded. As the golden standard reagent, glutaraldehyde (Glut) has been widely used to fix tissues and most commercial BHVs are manufactured from Glut-treated porcine or bovine pericardial tissues. However, some drawbacks such as calcification, coagulation, poor biocompatibility, endothelialization difficulties are still unresolved for the Glut-treated BHVs owing to the toxicity of Glut, which will severely shorten the durability of BHVs and emerge as a big challenge for its application in the younger-aged patients. In this work, BHVs treated by bicyclic hydromethyl-oxazolidine (OX-OH) has been successfully prepared from porcine pericardium (PP) tissue. Compared with Glut-treated PP (Glut-PP), beside the satisfactory physical and chemical properties similar to Glut-PP, OX-OH treated PP (OX-OH-PP) also exhibits excellent biocompatibility, reduced anti-calcification, improved anti-coagulation and proliferation of endothelial cells. In addition, OX-OH-PP has been processed to be a transcatheter aortic valve product, which exhibits desirable hydrodynamic performance and passes the durability test of more than 350 million times without any perforation, tearing and delamination, meeting the relevant industry standard for transcatheter aortic valve products. The excellent biocompatibility, reduced anti-calcification, improved anti-coagulation and endothelialization, and high durability make OX-OH-PP a great potential in the clinical applications of BHVs.