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

This study developed a multifunctional surface-engineering strategy for glutaraldehyde-crosslinked porcine pericardium used in bioprosthetic heart valves. Decellularized porcine pericardium was crosslinked with glutaraldehyde and sequentially modified with polyethyleneimine, a hyaluronic acid hydrogel coating, and polyethyleneimine-dextran sulfate nanoparticles to create a bionic interface designed to simultaneously improve anticoagulation, inflammation control, endothelialization, and resistance to calcification. The optimized PEI-DXS nanoparticles could be prepared at liter scale and retained stable morphology and particle size after storage at room temperature for up to 24 months. Hyaluronic acid-containing surfaces were substantially more hydrophilic and reduced protein and platelet adhesion, while the final GAPH@PD-PP material showed minimal thrombus formation during recalcified whole-blood and rabbit arterio-venous shunt testing. Surface modification also improved cytocompatibility and endothelialization, with GAPH@PD-PP supporting substantially greater L929 viability, HUVEC adhesion and proliferation, and VEGF secretion than unmodified GA-PP. In rat subcutaneous implantation, the HA-containing materials showed markedly reduced calcium deposition, while GAPH@PD-PP promoted a shift from pro-inflammatory M1 macrophages toward anti-inflammatory M2 macrophages and maintained this response over time. Tensile characterization demonstrated that the final modification retained and enhanced mechanical performance, with GAPH@PD-PP reaching an ultimate tensile strength of 24.4 ± 2.4 MPa, a tangent modulus of 240.8 MPa, and an elongation at break of 6.7%. Overall, the study demonstrates that topologically coupling a polysaccharide hydrogel coating with functional nanoparticles can produce a mechanically robust and multifunctional bioprosthetic heart valve material with improved hemocompatibility, endothelialization, immunomodulation, and anticalcification performance.