Catechol crosslinked bioprosthetic valves derived from caffeic acid and dopamine-conjugated porcine pericardia exhibit enhanced antithrombotic, immunomodulatory and anticalcification performance.

Abstract

The global aging population has led to an increasing prevalence of valvular heart disease (VHD), and the clinical application of bioprosthetic heart valves (BHVs) are growing with the advancement of transcatheter heart valve replacement surgery. However, BHVs, as xenogeneic pericardial tissue crosslinked with glutaraldehyde, have been affected by suboptimal cytocompatibility, thrombosis, immune response, and calcification, leading to premature degeneration and failure. Herein, a catechol-crosslinking strategy for BHVs was developed by conjugating porcine pericardia (PP) with catechols and subsequently coupling the grafted catechols to achieve the crosslinking and stabilization of BHVs. Caffeic acid and dopamine were exploited to conjugate the bioactive catechols on PP through amide condensation, and the catechols were further coupled under oxidation to impart the PP with enhanced stability and cytocompatibility as well as comparable mechanical properties to those of glutaraldehyde crosslinked PP (GLUT-PP). With the enrichment of catechols, the crosslinked PP not only demonstrated improved hydrophilicity to resist the blood components adhesion and thrombosis, but also enhanced the performance of endothelialization and antioxidation. Furthermore, the introduced catechols exhibits favorable anti-inflammatory properties, which significantly ameliorated the foreign body response and regulated the local immune responses of crosslinked PP. In conclusion, the catechol crosslinked PP is expected to be explored as a potential substitute for GLUT-PP to extend the lifespan of BHVs. STATEMENT OF SIGNIFICANCE: Bioprosthetic heart valves (BHVs) are mainly prepared from glutaraldehyde crosslinked porcine or bovine pericardia (GLUT-PP). Currently, BHVs are affected by cytotoxicity, thrombosis, calcification, and immunoinflammatory responses, which would accelerate degeneration and failure of BHVs. In this study, we developed a catechol crosslinking strategy for BHVs and engineered caffeic acid and dopamine-conjugated porcine pericardia (PP). In summary, catechol crosslinked porcine pericardia demonstrated enhanced collagen stability, antithrombosis, endothelialization, anticalcification and immunomodulation which reduced the risk of structural degeneration, suggesting that the catechol crosslinked porcine pericardia could serve as a potential alternative to GLUT-PP.