Sato Yasushi, Inoue Yusuke, Terazawa Takeshi, Nagayoshi Tomoki, Fujimoto Kazuto, Shiraishi Isao, Takamatsu Kensuke, Ohta Kunihiro, Takewa Yoshiaki
Advanced Medical Engineering Research Center, Asahikawa Medical University, 2-1-1-1 Midorigaoka higashi, Asahikawa, Hokkaido, 078-8510, Japan.
Department of Pediatric Cardiology, National Cerebral and Cardiovascular Center, 6-1 Kishibe-Shimmachi, Suita, Osaka, 564-8565, Japan.
J Artif Organs. 2025 May 26. doi: 10.1007/s10047-025-01507-w.
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.
经导管肺动脉瓣植入术（TPVI）是一种用于治疗先天性心脏病中肺动脉瓣功能障碍的微创手术。然而，异种生物瓣膜耐久性有限是一个重大问题。组织工程心脏瓣膜（TEHVs）已成为一种有前景的替代方案。我们利用基于组织包封的体内组织构建技术开发了一种自体TEHV——生物瓣膜。在本研究中，我们旨在开发可应用于TPVI的带支架生物瓣膜（支架生物瓣膜）。我们专门为TPVI设计了一种不对称沙漏形支架和一个笼状模具。将支架放置在芯棒上并用外笼覆盖，从而将其固定在模具内部。将带有支架的模具皮下植入2个月后，取出形成组织的模具以获得支架生物瓣膜。支架支柱完全被致密的胶原蛋白覆盖。支架生物瓣膜通过导管完整地插入和展开，并成功植入山羊肺动脉瓣位置。植入后未出现狭窄、反流或移位等并发症，在未进行抗凝治疗的情况下存活约6个月，具有良好的生物相容性和潜在的抗血栓特性。在切除的生物瓣膜中未发现血栓或钙化的显著迹象，宿主组织的细胞迁移表明组织正在进行重塑。使用带有外笼的新型模具可确保支架整合，无论支架形状如何都能生产生物瓣膜。本研究提出了一种应对经导管心脏瓣膜植入挑战的有前景策略。
