Polyzwitterion-crosslinked hybrid tissue with antithrombogenicity, endothelialization, anticalcification properties

Abstract

Although transcatheter aortic valve implantation (TAVI) has been proven with excellent effectiveness and safety, the subclinical leaflet thrombosis (SLT) and structural valve deterioration (SVD) are two main factors threatening the service lifespan of the transcatheter aortic valve (TAV) because the glutaraldehyde (Glut) crosslinked tissue as leaflet material for the current clinically used TAV has high calcification propensity and thrombogenicity. In this study, zwitterionic monomer sulfobetaine methacrylate (SBMA) and methacrylated porcine pericardium (MA-PP) were in situ copolymerized to obtain zwitterionic-polymer/ tissue hybrid (PSBMA-PP). The hybrid PP showed high collagen stability, appropriate mechanical property, and anti-fatigue performance, meeting the essential requirements as a TAV leaflet. Moreover, the assays of platelet adhesion, in vitro thrombus generation, and ex vivo arteriovenous shunt (AV-shunt) assay suggested that PSBMA-PP had significantly lower thrombogenicity than the non-hybrid porcine pericardium (PMA-PP) and glutaraldehyde crosslinked porcine pericardium (Glut-PP). Interestingly, the introduction of poly-SBMA increased the resistance to the adsorption of non-specific proteins but didn’t compromise the endothelialization potential, promisingly benefitting the long-term hemocompatibility. Meanwhile, the subcutaneous implantation in rats for 120 days showed that PSBMA-PP was able to effectively inhibit the calcification of valve leaflets compared with Glut-PP, which was significant to retard the occurrence of SVD. In conclusion, we developed a simple method to simultaneously functionalize and crosslink the tissue with robust antithrombotic and anticalcification properties for the fabrication of TAV, which was expected to further improve the safety and service life of existing interventional TAV products.