Interface engineering to enhance properties of bioprosthetic heart valve materials with polysaccharide nanocomposite-conjugated hydrogels.

Abstract

Heart valve disease poses a significant threat to human health, and the limitations of pharmacological interventions have led to heart valve replacement as an increasingly important therapeutic approach. However, the widely used glutaraldehyde cross-linked bioprosthetic heart valves are associated with several clinical problems, including thrombosis, chronic inflammation, calcification, and endothelial dysfunction, which seriously compromise their long-term efficacy. To overcome these issues, we develop an innovative functional surface engineering strategy performed sequentially at the molecular level. The proposed approach leverages the synergistic integration of a hyaluronic acid (HA) hydrogel coating and polyethyleneimine-dextran sulfate nanoparticles (PD NPs) to construct a bionic cascade functional interface. The HA hydrogel coating provides a hydrophilic barrier to decrease the risk of thrombosis and inflammation, while also mimicking the structure of the vascular endothelial glycocalyx to promote endothelial regeneration and block calcium ion deposition physically. PD NPs offer immediate anticoagulation and are chemically linked with hyaluronic acid to create a durable anti-inflammatory and slow-release network. By utilizing only three fundamental components (polyethyleneimine, dextran sulfate, and hyaluronic acid), this method integrates anticoagulant, anti-inflammatory, anti-calcification, and pro-endothelialization functions via a single surface modification. The topological coupling of the nanocarrier-hydrogel structure overcomes the constraints of traditional multi-step modifications and functional antagonism. It is worth noting that this functional system exhibits long-term stability, retaining structural integrity for over 2 years at room temperature, and is readily scalable for industrial application, presenting a promising solution to enhance the clinical performance of bioprosthetic heart valves. STATEMENT OF SIGNIFICANCE: Heart valve disease poses a significant threat to human health, and the limitations of pharmacological interventions have led to heart valve replacement as an increasingly important therapeutic approach. However, the widely used glutaraldehyde cross-linked bioprosthetic heart valves (BHVs) are associated with several clinical problems, including thrombosis, chronic inflammation, calcification, and endothelial dysfunction, which seriously compromise their long-term efficacy. To overcome these issues, an innovative functional surface engineering strategy performed sequentially at the molecular level has been developed. The proposed approach leverages the synergistic integration of a hyaluronic acid hydrogel coating and polyethyleneimine-dextran sulfate nanoparticles to construct a bionic cascade functional interface, enhancing the antithrombotic and anti-inflammatory properties and enabling comprehensive regulation of acute and chronic inflammation for BHV materials.