Transcatheter valve replacement indication is currently being extended to younger and lower-risk patients. However, transcatheter prostheses are still based on glutaraldehyde-fixed xenogeneic materials. Hence, they are prone to calcification and long-term structural degeneration, which are particularly accelerated in younger patients. Tissue-engineered heart valves based on decellularized in vitro grown tissue-engineered matrices (TEM) have been suggested as a valid alternative to currently used bioprostheses, showing good performance and remodeling capacity as transcatheter pulmonary valve replacement (TPVR) in sheep. Here, we first describe the in vitro development of human cell-derived TEM (hTEM) and their application as tissue-engineered sinus valves (hTESVs), endowed with Valsalva sinuses for TPVR. The hTEM and hTESVs were systematically characterized in vitro by histology, immunofluorescence, and biochemical analyses, before they were evaluated in a pulse duplicator system under physiological pulmonary pressure conditions. Thereafter, transapical delivery of hTESVs was tested for feasibility and safety in a translational sheep model, achieving good valve performance and early cellular infiltration. This study demonstrates the principal feasibility of clinically relevant hTEM to manufacture hTESVs for TPVR.

经导管瓣膜置换术的适应证目前正在扩大至年轻和低危患者。然而，经导管假体仍然基于戊二醛固定的异种材料。因此，它们易于钙化和长期结构变性，在年轻患者中尤其容易加速。已经提出了基于脱细胞的体外生长的组织工程基质（TEM）的组织工程心脏瓣膜作为目前使用的生物假体的有效替代方案，它具有良好的性能和重塑能力，可作为绵羊经导管肺动脉瓣置换术（TPVR）的替代。在这里，我们首先描述人源性TEM（hTEM）的体外发育及其作为组织工程性窦瓣（hTESVs）的应用，并赋予Valsalva鼻窦用于TPVR。hTEM和hTESV在体外通过组织学，免疫荧光和生化分析进行了系统表征，然后在生理肺压条件下在脉冲复制器系统中对其进行了评估。此后，在经转化的绵羊模型中，对经hTESVs的经心尖递送的可行性和安全性进行了测试，获得了良好的瓣膜性能和早期的细胞浸润。这项研究证明了临床相关的hTEM生产用于TPVR的hTESV的主要可行性。实现良好的瓣膜性能和早期细胞浸润。这项研究表明临床相关hTEM生产用于TPVR的hTESV的主要可行性。实现良好的瓣膜性能和早期细胞浸润。这项研究表明临床相关hTEM生产用于TPVR的hTESV的主要可行性。