Double-crosslinked carrageenan/gelatin hydrogel loaded with heparin for heart valve tissue engineering applications

The development of tissue-engineered heart valves (TEHVs) remains a challenge worldwide. In this study, a series of double-crosslinked methacrylated carrageenan (CA)/methacrylated gelatin (GelMA) hydrogels loaded with heparin (CA/Gel@Hep) were developed as potential materials for TEHV. CA/Gel@Hep hydrogels with different concentrations of heparin were fabricated, and their mechanical properties, swelling/degradation behaviors, and heparin release profiles, and biological performance were systematically studied. The rheological tests showed that storage modulus (G') was consistently higher than loss modulus (G''). Unconfined compression tests showed that the compressive modulus of CA/Gel@Hep hydrogels ranged from 0.26 ± 0.01 to 0.43 ± 0.03 kPa, which matches the mechanical requirements of native valve leaflets. In vitro evaluation demonstrated that CA/Gel@Hep hydrogels exhibited good cytocompatibility and blood compatibility, excellent anticoagulant properties, and facilitated migration, proliferation and osteogenic differentiation of human adipose tissue-derived mesenchymal stromal cells (hADMSCs). qPCR results showed that CA/Gel@Hep hydrogels significantly upregulated the expression of genes related to valve remodeling, including SMA, VIM, MMP1, and MMP2. These results suggest that CA/Gel@Hep hydrogels hold great potential for heart valve tissue engineering applications.