A nitric oxide-releasing zwitterionic glycocalyx-mimetic hydrogel armored bioprosthetic valve with integrated antithrombotic, endothelialization-promoting, and immunomodulatory capacities

This study developed a nitric oxide-releasing, zwitterionic glycocalyx-mimetic hydrogel coating for glutaraldehyde-crosslinked porcine pericardium used in bioprosthetic heart valves. The authors first decellularized porcine pericardium and crosslinked it with glutaraldehyde to produce G-P, then photopolymerized a hyaluronic acid- and sulfobetaine methacrylate-based hydrogel coating onto the tissue to create HS-P. L-arginine was subsequently incorporated into the coating through dynamic Schiff-base chemistry to create AHS-P and provide a nitric oxide-generating function. The hydrogel coating substantially increased surface hydrophilicity and reduced nonspecific protein, platelet, erythrocyte, and whole-blood adhesion while preserving the underlying tissue’s tensile mechanical properties. L-arginine-functionalized AHS-P promoted HUVEC adhesion and proliferation, increased nitric oxide, VEGF, and VWF production, and activated pathways associated with endothelial adhesion and growth, including RhoA-ROCK and PI3K/AKT/mTOR signaling. AHS-P also reduced inflammatory signaling, lowering TNF-α and promoting IL-10 expression and M2 macrophage polarization in vitro and after rat subcutaneous implantation. Calcification was markedly reduced in hydrogel-coated samples: after 90 days of implantation, calcium content was 226 ± 6 mg/g in unmodified G-P compared with 15 ± 2 mg/g in HS-P and 14 ± 2 mg/g in AHS-P. Mechanical testing showed no significant differences among G-P, HS-P, and AHS-P in ultimate tensile strength, tangent modulus, or extensibility, indicating that the surface modification preserved the structural mechanical performance of the pericardial tissue. Overall, the study demonstrates a multifunctional surface-engineering strategy that combines antithrombotic, endothelialization-promoting, immunomodulatory, and anticalcification functions without compromising the tensile properties required for bioprosthetic heart valve materials.