Abstract 4141282: Cystamine/Pentagalloylglucose-based versatile modification strategy of decellularized porcine pericardium for transcatheter tissue engineered heart valves

Transcatheter valve replacement has become the preferred treatment for high-risk elderly patients considering the advantages of less invasive surgical trauma and faster postoperative recovery. Transcatheter heart valves (THVs) primarily made of glutaraldehyde-crosslinked pericardial materials pose a risk of thrombosis and calcification, and are subjected to additional stress during catheter delivery, which leads to poor durability. Herein, we constructed a novel transcatheter tissue engineered heart valve for in situ regeneration through functional modification of cystamine (CySA) and pentagalloylglucose (PGG) on decellularized porcine pericardium (DPP), referred to as CySA/PGG-PP. A dynamically reversible fiber network structure was formed by the modification of CySA and PGG, resulting in excellent resistance to enzymatic degradation and crimping stability of CySA/PGG-PP. The distinctive capability of CySA to catalyze the production of endogenous nitric oxide (NO) provided CySA/PGG-PP with a long-term NO release system that inhibited platelet adhesion and activation to improve hemocompatibility. Proteomics analysis revealed that the improvement of hemocompatibility might be mediated by protein phosphorylation and arachidonic acid metabolism-related pathways. Furthermore, we found that CySA/PGG-PP exhibited significant recellularization and tissue remodeling in a rat abdominal aortic implantation model, accompanied by a mild inflammatory response and no calcification. The positive results in vivo might be regulated by genes associated with cell adhesion and differentiation, extracellular matrix organization, and TGF-β signaling pathway, as revealed by RNA sequencing. Consequently, the instructive transcatheter tissue-engineered valve overcomes the limitations of existing THVs with the aim of significantly improving valve durability for clinical therapy.