Reactive Oxygen Species-Responsive Glycocalyx-Mimetic Hydrogel-Engineered Bioprosthetic Valves with Integrated Anticoagulant, Anti-Inflammatory, and Endothelialization Properties.

Abstract

The rise of transcatheter valve therapy has sharply expanded the worldwide need for bioprosthetic heart valves (BHVs). However, several persistent challenges remain unresolved, including suboptimal cytocompatibility, thrombogenicity, and adverse immune responses. Herein, a reactive oxygen species (ROS)-responsive glycocalyx-mimetic hydrogel-engineered BHV (RA/Hep-GAP) with integrated anticoagulant and anti-inflammatory properties was constructed. Thiolated glutaraldehyde cross-linked pericardium was prepared by multicomponent co-cross-linking, followed by the construction of a glycocalyx-like coating via Michael addition and radical polymerization, and subsequently loaded with anti-inflammatory and anticoagulant drugs (rosmarinic acid and heparin) to obtain RA/Hep-GAP. Glycocalyx-like coating not only serves as a scaffold to support HUVEC growth and promote endothelialization but also shields the collagen matrix, thereby synergizing with heparin's active regulation of the coagulation cascade to reduce the risk of thrombus formation. The incorporation of rosmarinic acid via dynamic phenylboronic ester bonds facilitates ROS scavenging to enhance the antioxidant capacity of BHV, while rosmarinic acid modulates inflammatory progression via regulation of key genes (Lcn2, C1ra, Saa3, Hmox1, Adm, and Dusp5). Furthermore, RA/Hep-GAP demonstrated improved anticalcification properties following rat subcutaneous implantation. This work opens a potential approach to BHV modification that may lessen the degeneration risk.