Hayashida Kyoko, Kanda Keiichi, Yaku Hitoshi, Ando Joji, Nakayama Yasuhide
Department of Bioengineering, Advanced Medical Engineering Center, National Cardiovascular Center Research Institute, Osaka, Japan.
J Thorac Cardiovasc Surg. 2007 Jul;134(1):152-9. doi: 10.1016/j.jtcvs.2007.01.087.
This study aimed to develop an autologous heart valve without using traditional in vitro tissue-engineering methods, which necessitate complicated cell management protocols under exceptionally clean laboratory facilities.
An autologous heart valve construct composed of trileaflets was prepared using a specially designed mold. The mold was prepared by covering a silicone rod with a crown-shaped tubular polyurethane scaffold containing 3 horns. The mold was implanted in the dorsal subcutaneous space in Japan White rabbits for 4 weeks. After harvesting, the implanted trileaflet valve-shaped structure with an internal diameter of either 5 or 20 mm was obtained by trimming the membranous tissue formed between the horns located around the silicone rod. The valve substitute was examined both macroscopically and histologically. The tensile strength of the leaflets was measured to rupture. The degree of regurgitation in valve function was evaluated using a flow circuit by calculating the ratio of the regurgitation volume to the forward flow volume.
After implantation, the mold was completely covered with connective tissue consisting mostly of collagen and fibroblasts. Harvesting of the mold was straightforward, because there was little adhesion between the formed tissue and the native skin tissue. The trileaflet heart valve construct was obtained after withdrawing the inserted rods and trimming the membranous tissues formed between the horns of the scaffold. It was firmly attached to the scaffold, the interstices and surface of which revealed connective tissues composed of components similar to those of the leaflet tissue. Although the mechanical properties of the leaflet tissue were less efficient than those of the native porcine aortic valve leaflets, satisfactory valvular functions were demonstrated under pulsatile conditions using a flow circuit. No regurgitation was observed under retrograde hydrostatic pressures of up to 60 mm Hg, the physiologic pressure acting on the aortic valves during retrograde aortic flow.
The biovalve, an autologous, in vivo tissue-engineered, trileaflet, valve-shaped construct, was developed using our novel in-body tissue architecture technology. The biovalve has the potential to be an ideal prosthetic heart valve, with excellent biocompatibility to the growth of the recipient's heart.
本研究旨在开发一种不使用传统体外组织工程方法的自体心脏瓣膜，传统方法需要在极其洁净的实验室设施下进行复杂的细胞管理方案。
使用特殊设计的模具制备由三叶瓣组成的自体心脏瓣膜构建体。该模具通过用含有3个角的冠状管状聚氨酯支架覆盖硅胶棒制备而成。将模具植入日本白兔的背部皮下空间4周。收获后，通过修剪位于硅胶棒周围角之间形成的膜状组织，获得内径为5或20毫米的植入三叶瓣瓣膜形状结构。对瓣膜替代物进行宏观和组织学检查。测量瓣叶的拉伸强度直至破裂。使用流动回路通过计算反流体积与正向流体积的比率来评估瓣膜功能中的反流程度。
植入后，模具完全被主要由胶原蛋白和成纤维细胞组成的结缔组织覆盖。模具的收获很简单，因为形成的组织与天然皮肤组织之间几乎没有粘连。拔出插入的棒并修剪支架角之间形成的膜状组织后，获得了三叶心脏瓣膜构建体。它牢固地附着在支架上，支架的间隙和表面显示出由与瓣叶组织类似成分组成的结缔组织。尽管瓣叶组织的机械性能不如天然猪主动脉瓣叶，但在使用流动回路的脉动条件下显示出令人满意的瓣膜功能。在高达60毫米汞柱的逆行静水压力下未观察到反流，这是逆行主动脉血流期间作用于主动脉瓣的生理压力。
使用我们新颖的体内组织结构技术开发了双瓣膜，这是一种自体、体内组织工程化的三叶瓣膜形状构建体。双瓣膜有可能成为理想的人工心脏瓣膜，对受体心脏的生长具有优异的生物相容性。
