Polyphenol based hybrid nano-aggregates modified collagen fibers of biological valve leaflets to achieve enhanced mechanical, anticoagulation and anti-calcification properties

Glutaraldehyde (Glut)-crosslinked porcine pericardium and bovine pericardium are mainly consisted of collagen and widely used for the preparation of heterogenous bioprosthetic heart valves (BHV), which play an important role in the replacement therapy of severe valvular heart disease, while their durability is limited by degeneration due to calcification, thrombus, endothelialization difficulty and prosthetic valve endocarditis. Herein, we develop a novel BHV, namely, TPly-BP, based on natural tannic acid and polylysine to improve the durability of Glut crosslinked bovine pericardium (Glut-BP). Impressively, tannic acid and polylysine could form nanoaggregates via multiple hydrogen bonds and covalent bonds, and the introduction of nanoaggregates not only improved the mechanical properties and collagen stability but also endowed TPly-BP with good biocompatibility and hemocompatibility. Compared to Glut-BP, TPly-BP showed significantly reduced cytotoxicity, improved endothelial cell adhesion, a low hemolysis ratio and obviously reduced platelet adhesion. Importantly, TPly-BP exhibited great antibacterial and in vivo anti-calcification ability, which was expected to improve the in vivo durability of BHVs. These results suggested that TPly-BP would be a potential candidate for BHV.