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Implanted In-Body Tissue-Engineered Heart Valve Can Adapt the Histological Structure to the Environment

Takewa, Yoshiaki*; Sumikura, Hirohito*; Kishimoto, Satoru*; Naito, Noritsugu*; Iizuka, Kei*; Akiyama, Daichi*; Iwai, Ryosuke; Tatsumi, Eisuke*; Nakayama, Yasuhide*

doi: 10.1097/MAT.0000000000000769
Tissue Engineering/Biomaterials
Conference Article

Tissue-engineered heart valves (TEHVs) are expected to be viable grafts. However, it is unknown whether they transit their histological structure after implantation. We developed a novel autologous TEHV (named stent biovalve) for transcatheter implantation, using in-body tissue engineering based on a tissue encapsulation phenomenon. In this study, a time-course histological transition of implanted biovalves was investigated in goats. Three types of stent biovalves were prepared by 2 month embedding of plastic molds mounted with metallic stents, in the subcutaneous spaces. After extracting the molds with tissue and removing the molds only, stent biovalves were constituted entirely from the connective tissues. Stent biovalves were implanted in the aortic or pulmonary valve position of other goats with transcatheter technique. In each animal, the stent biovalve was explanted at 1 month step (from 1 to 6 months) or as long as possible. Total 12 goats (five for aortic and seven for pulmonary) were successfully implanted. The maximum duration became 19 months as a result. Even then the leaflets of the biovalves kept their shape and elasticity, and neither calcification nor thrombi were observed in any cases and duration. Histology showed the recipients’ cells covering the laminar surface of the leaflets like the endothelium even after 1 month. The cells have also migrated in the leaflets gradually and finally constructed characteristic 3 layered tissues like native leaflets. Implanted stent biovalves can adapt their histological structure to the environment. They have a potential as viable grafts keeping better function and biocompatibility.

From the *Department of Artificial Organs, National Cerebral and Cardiovascular Center Research Institute, Osaka, Japan

Department of Bioengineering, Research Institute of Technology, Okayama University of Science, Okayama, Japan.

Disclosure: The authors have no conflicts of interest to report.

Submitted for consideration June 2017; accepted for publication in revised form February 2018.

This study was supported by JSPS KAKENHI Grant Number JP15H04940.

Correspondence: Yasuhide Nakayama and Yoshiaki Takewa, 5-7-1 Fujishiro-dai, Suita, Osaka 565–8565, Japan. Email: and

Copyright © 2018 by the American Society for Artificial Internal Organs