RESEARCH SUMMARY
This study developed an inflammation-responsive, glycocalyx-mimetic hydrogel surface modification for decellularized porcine pericardium intended for bioprosthetic heart valves. The authors first introduced catechol groups onto porcine pericardium and then oxidatively coupled dopamine-modified sodium alginate to create a glycocalyx-like hydrogel coating. Baicalin-loaded, reactive oxygen species-responsive nanoparticles were subsequently immobilized onto the coating through catechol-amine chemistry, producing BA@ALG-PP. The resulting construct combined non-glutaraldehyde matrix crosslinking, a hydrophilic antithrombotic surface, ROS scavenging, and inflammation-responsive baicalin delivery. BA@ALG-PP released approximately 87% of its loaded baicalin over 14 days under 100 µM H2O2 and exhibited improved resistance to collagenase degradation compared with conventional glutaraldehyde-crosslinked pericardium. Importantly, hydrogel functionalization preserved valve-tissue mechanical performance: BA@ALG-PP exhibited an ultimate tensile strength of 21.6 ± 0.8 MPa, fracture strain of 0.54 ± 0.07, tangent modulus of 56 ± 6 MPa, and extensibility of 0.25 ± 0.03, values broadly comparable with glutaraldehyde-crosslinked tissue. The hydrogel-functionalized materials also showed substantially improved hydrophilicity, reduced protein and platelet adhesion, minimal hemolysis, enhanced endothelial-cell adhesion, and reduced thrombus formation under ex vivo blood circulation. Baicalin-functionalized samples demonstrated strong antioxidant activity and shifted macrophage responses toward an anti-inflammatory M2 phenotype through regulation of pathways including NF-κB, MAPK, and JAK-STAT. Rabbit intravascular implantation supported improved endothelialization and antithrombotic performance, while rat subcutaneous implantation showed substantially reduced inflammatory infiltration and calcification through 90 days. Overall, the study demonstrates that an ROS-responsive drug-delivering glycocalyx-mimetic hydrogel can add antithrombotic, antioxidant, immunomodulatory, endothelialization-promoting, and anticalcification functions to porcine-pericardial bioprosthetic valve material without substantially compromising its tensile mechanical properties.
A CellScale BioTester was used for uniaxial tensile characterization of decellularized and surface-functionalized porcine pericardium. PP, glutaraldehyde-crosslinked GLUT-PP, catechol-modified CA-PP, alginate-hydrogel-coated ALG-PP, and baicalin-loaded BA@ALG-PP samples were cut into 50 × 7 mm strips. Thickness was measured at three locations and averaged, and the initial grip-to-grip length was recorded before loading. Specimens were stretched at 20 mm/min until failure while tensile force and instantaneous length were continuously recorded. The measurements were converted to Cauchy stress and Green strain and used to determine ultimate tensile strength, fracture strain, tangent modulus, and extensibility. BA@ALG-PP achieved an ultimate tensile strength of 21.6 ± 0.8 MPa, similar to ALG-PP at 20.7 ± 0.8 MPa and glutaraldehyde-crosslinked pericardium at 19.6 ± 2.8 MPa. Corresponding fracture strains were 0.54 ± 0.07, 0.55 ± 0.16, and 0.65 ± 0.08, while tangent moduli were 56 ± 6, 67 ± 8, and 63 ± 16 MPa, respectively. Extensibility was likewise comparable among the crosslinked groups. The mechanical assay also showed similar suture pull-out strengths across GLUT-PP, CA-PP, ALG-PP, and BA@ALG-PP. These BioTester measurements demonstrated that introducing the glycocalyx-mimetic hydrogel and ROS-responsive baicalin delivery system did not significantly compromise the tensile integrity of the pericardial matrix, supporting its potential use under the cyclic mechanical demands encountered by bioprosthetic heart-valve leaflets.
