Microenvironment-Responsive Biomimetic Bioprosthetic Valve with Antithrombosis and Immunoregulation Performance

Abstract

The prevalence of heart valve disease (HVD) has escalated worldwide, because of population aging. Currently, artificial heart valve replacement is considered the most effective treatment for HVD. The complexity and risk of heart valve replacement have been markedly reduced with the development of minimally invasive interventional techniques, which has resulted in the more widespread implantation of bioprosthetic heart valves (BHVs); however, they still present with defects including thrombosis, poor cytocompatibility, immune responses, and calcification, which reduces their service life. We developed a microenvironment-responsive zwitterionic glycocalyx-mimetic hydrogel-engineered BHV (Hes@HS-PP) with a profile of on-demand drug release. Inspired by the structure and function of the glycocalyx on the inner wall of blood vessels, a zwitterionic glycocalyx-mimetic hydrogel coating was covalently constructed on the BHV by photoinduced polymerization. This coating significantly resisted the fouling of blood components and thrombosis and improved the endothelialization potential and biocompatibility of BHVs by shielding the interactions between blood and the xenogeneic collagenous BHV matrix. Following the introduction of dynamic borate ester bonds into the hydrogel, the anti-inflammatory drug hesperidin (Hes) was loaded onto the BHVs. Excess reactive oxygen species were scavenged, and Hes was released into the inflammatory region on demand to achieve immune regulation and ameliorate inflammatory reactions on BHVs. Moreover, Hes@HS-PP exhibited a markedly lower degree of calcification in a rat subcutaneous implantation model. In summary, the construction of microenvironment-responsive zwitterionic glycocalyx-mimetic hydrogels on BHVs significantly enhanced their antithrombotic, anti-inflammatory, endothelialization, and anticalcification properties and mitigated the risk of structural valvular degradation, offering new perspectives for the functional modification of BHVs.