In Situ Heart Valve Tissue Engineering Using a Bioresorbable Elastomeric Implant: From Material Design to 12-Month Follow-Up in Sheep

This landmark study establishes a synthetic, cell-free, resorbable elastomeric heart valve that regenerates in situ by recruiting host cells. The valve scaffold, fabricated from a polycarbonate-bisurea (PC-BU) supramolecular elastomer, was electrospun into fibrous leaflets and sutured to a PEEK ring. The elastomer was engineered for controlled degradation, elasticity, and cell-driven remodeling. Sheep received pulmonary valve replacements and were monitored for up to 12 months. All valves remained hemodynamically functional with minimal regurgitation and no calcification or thrombosis. Histological analysis revealed progressive infiltration by vimentin⁺ and α-SMA⁺ interstitial cells, development of a confluent endothelium (CD31⁺), and deposition of collagen, GAGs, and mature elastin fibers matching native tissue composition. By 12 months, the scaffold had partially resorbed where cellular activity was highest, leaving behind organized neo-tissue with native-like mechanical anisotropy. Transcatheter (Nitinol-stented) implantation was also demonstrated as feasible with full valve function for 6 months post-implantation. The study provides the first full demonstration of in situ regeneration of a functional, durable, and bioresorbable heart valve starting from a purely synthetic material.