Silk Sericin is a Potent, Multifunctional Biomaterial for Endothelialization of Tissue‐Engineered Heart Valves

Abstract Endothelialization is important for offering an anticoagulant surface, which is crucial for the construction of tissue‐engineered heart valves. Silk sericin is extensively investigated in the biomedical field due to its remarkable biological activities and diverse functional groups, favoring chemical modifications for the formation of versatile constructs. Herein, a sericin covalently modified valve (SCMV) is successfully fabricated by coupling maleylated silk sericin (MSS) with thiolated decellularized heart valve (DHV) through a Michael addition reaction. The results demonstrate that SCMV exhibits a smooth surface, higher hydrophilicity, and excellent resistance to platelets adhesion compared to DHV. Additionally, SCMV promotes endothelial cells (ECs) adhesion under both static and flow conditions and enhances their survival in a mouse subcutaneous implant model. The study also discovered that MSS‐stimulated ECs exhibit increased RhoA activation, expression of rho‐associated protein kinase 2 (ROCK2) and phosphorylated myosin light chain 2 (MLC2), actin polymerization, and cell adhesion; whereas actin organization and cell adhesion are significantly reduced by treatment with Y‐27632, a ROCK inhibitor. Furthermore, several integrin subunits, including α1, α2, α3, α5, α6, β1, β3, and β5, are involved in this regulatory process. Collectively, the findings highlight the potential application of silk sericin in promoting endothelialization of DHV while uncovering novel mechanisms underlying its regulatory effect on ECs adhesion.