Acute Phase Pilot Evaluation of Small Diameter Long iBTA Induced Vascular Graft "Biotube" in a Goat Model

Ryuji Higashita; Yasuhide Nakayama; Yasuyuki Shiraishi; Ryosuke Iwai; Yusuke Inoue; Akihiro Yamada; Takeshi Terazawa; Tsutomu Tajikawa; Manami Miyazaki; Mamiko Ohara; Tadashi Umeno; Keitaro Okamoto; Tomonori Oie; Tomoyuki Yambe; Shinji Miyamoto

doi:10.1016/j.ejvsvf.2022.01.004

Acute Phase Pilot Evaluation of Small Diameter Long iBTA Induced Vascular Graft "Biotube" in a Goat Model

EJVES Vasc Forum. 2022 Jan 11:54:27-35. doi: 10.1016/j.ejvsvf.2022.01.004. eCollection 2022.

Authors

Affiliations

¹ Department of Cardiovascular Surgery, Yokohama General Hospital, Kanagawa, Japan.
² Osaka Laboratory, Biotube Co., Ltd., Osaka, Japan.
³ Pre-Clinical Research Centre, Institute of Development Ageing and Cancer, Tohoku University, Miyagi, Japan.
⁴ Institute of Frontier Science and Technology, Okayama University of Science, Okayama, Japan.
⁵ Advanced Medical Engineering Research Centre, Asahikawa Medical University, Hokkaido, Japan.
⁶ Department of Mechanical Engineering, Faculty of Engineering Science, Kansai University, Osaka, Japan.
⁷ Department of Nephrology, Kameda Medical Centre, Chiba, Japan.
⁸ Department of Cardiovascular Surgery, Oita University Hospital, Oita, Japan.

Abstract

Objective: There is a need for small diameter vascular substitutes in the absence of available autologous material. A small diameter, long tissue engineered vascular graft was developed using a completely autologous approach called "in body tissue architecture technology (iBTA)". The aim of this pilot study was to evaluate "Biotubes", iBTA induced autologous collagenous tubes, for their potential use as small diameter vascular bypass conduits.

Methods: Biotubes (internal diameter 4 mm, length 50 cm, wall thickness 0.85 mm) were prepared by subcutaneous embedding of plastic moulds (Biotube Maker) in three goats for approximately two months. Allogenic Biotubes (length 10 cm [n = 2], 15 cm [n = 2], 22 cm [n = 2]) were bypassed to both carotid arteries by end to side anastomosis with their ligation between the anastomoses in another three goats. Residual Biotubes were examined for their mechanical properties. After four weeks, the harvested Biotubes were evaluated histologically.

Results: All Biotubes had sufficient pressure resistance, approximately 3000 mmHg. Although wall thickening occurred at two proximal anastomosis sites, all six grafts were patent without luminal thrombus formation, stenosis, or aneurysm deformation throughout the implantation period. Endothelial cells covered both anastomosis sites almost completely, with partial covering in the central portion of the grafts. Furthermore, α smooth muscle actin positive cells infiltrated the middle layer along almost the entire graft length.

Conclusion: This preliminary study showed that small diameter, long, tissue engineered Biotubes could function properly as arterial bypass conduits in a large animal for one month without any abnormal change in vascular shape. Thus, small diameter, long Biotubes are potentially viable conduits, which are biocompatible and labour non-intensive, and therefore, suitable for clinical practice. Additionally, Biotubes can start the regeneration process in a short period of time.

Keywords: Biotube; Chronic limb threatening ischaemia; In body tissue architecture; Small diameter artificial vascular graft; Tissue engineered vascular graft.