Development of transcatheter implantable autologous tissue-engineered pulmonary valves using in-body tissue architecture.

Transcatheter pulmonary valve implantation (TPVI) is a minimally invasive procedure used to treat pulmonary valve dysfunction in congenital heart disease. However, the limited durability of xenogeneic bioprosthetic valves is a significant concern. Tissue-engineered heart valves (TEHVs) have emerged as a promising alternative. We developed an autologous TEHV, Biovalve, using an in-body tissue architecture technology based on tissue encapsulation. In this study, we aimed to develop stent-integrated Biovalves (stent Biovalves) that can be applied to TPVI. We designed an asymmetric hourglass-shaped stent and a caged mold specifically for TPVI. The stent was fixed inside the mold by placing it on a core rod and covering it with an outer cage. After subcutaneous implantation of the molds with stents for 2 months, the molds with formed tissue were harvested and removed to obtain the stent Biovalve. The stent struts were completely covered with dense collagen. The stent Biovalve demonstrated intact insertion and deployment via the catheter and was successfully implanted in the goat pulmonary valve location. No complications such as stenosis, regurgitation, or translocation occurred post-implantation, with about 6 months of survival without anticoagulant therapy, excellent biocompatibility, and potential antithrombotic properties. There were no significant findings of thrombus or calcification in the excised Biovalve, and cell migration from the host tissue indicated ongoing tissue remodeling. Utilizing a novel mold with an outer cage ensures stent integration, enabling Biovalve production regardless of stent shape. This study presents a promising strategy to address the challenges of transcatheter heart valve implantation.