Long‐term animal implantation study of biotube‐autologous small‐caliber vascular graft fabricated by in‐body tissue architecture

Abstract

A mold for the preparation of an in-body tissue architecture-induced autologous vascular graft, termed "biotube," was prepared by covering a main silicone rod (outer diameter, 3 mm; length, 30 mm) with two pieces of polyurethane sponge tubes (internal diameter, 3 mm; length, 3 mm) at both ends. The molds were embedded into the dorsal subcutaneous pouch of rabbits (weighing ca. 2 kg) for 2 months. After harvesting the rods with the formed surrounding tissues, the rods were removed to create biotubes impregnated with anastomotic reinforcement cuffs at both ends. The biotubes had homogeneous, thin connective tissue wall (thickness, 76 ± 37 μm) that was primarily composed of collagen and fibroblasts. One biotube was loaded with argatroban and autoimplanted in the carotid artery for 26 months. Neither antiplatelet nor anticoagulant agents were administered, except for an intraoperative heparin injection. Follow-up angiography showed no aneurysm formation, rupturing, or stenosis during implantation. At the end of implantation, the wall thickness of biotube (212 ± 24 μm at the anastomosis portion and 150 ± 14 μm at the midportion) was similar to that of native artery (189 ± 23 μm). The luminal surface was completely covered with endothelial cells on the formed lamina elastica interna-like layer. The regenerated vascular walls comprised multilayered smooth muscle cells and dense collagen fibers with regular circumferential orientation. A remarkable multilayered elastin fiber network was observed near the anastomosis portion. Biotubes could thus be used as small-caliber vascular prostheses that greatly facilitate the healing process and exhibit excellent biocompatibility.

In-body tissue-engineered aortic valve (Biovalve type VII) architecture based on 3D printer molding

“…This technology has been previously used for the development of cardiovascular tissues with vascular grafts, namely Biotubes. 13,15 The Biotubes were formed within a relatively short period (4 weeks) after embedding rod-like molds into subcutaneous pouches because the whole mold surfaces were attached directly to the subcutaneous tissue. In comparison, since tissue migration into a small aperture is slow, leaflet formation in the Biovalves took longer, following the formation of the conduit.…”

“…This would be similar to that demonstrated in the previous studies of pulmonary valve replacement with Biovalves 10 or the vascular implantation of Biotubes. 12,15 CONCLUSION 3D printing was successfully demonstrated to be useful in the fabrication of the fine components required to create Biovalve molds. Biovalves, with sinuses of Valsalva, obtained from the mold satisfied the highly specialized systemic circulation requirements in vitro and in vivo.…”

Development of tissue‐engineered self‐expandable aortic stent grafts (Bio stent grafts) using in‐body tissue architecture technology in beagles

“…15 In addition, the production of vascular wall cells and appropriate orientation of the extracellular matrix were detected at 3 months after graft implantation. 15,16 Based on these findings, we believe that the Bio stent graft will exhibit similar in vivo findings-that is, migration of the native cells such as endothelial cells or smooth muscle actin-positive cells to the Bio stent graft wall, which leads to a strong attachment between the graft wall and the aorta. Such in vivo adaptation may not be seen in extremely early phase after implantation, though if it occurs in the landing zone of the stent graft in several weeks, it would be possible to achieve tighter graft fixation and long-term excellent conformability even in angulated or short landing zones.…”

“…We have demonstrated the functionality and excellent durability of in vivo tissue-engineered vascular grafts (Biotubes) 16 and valves (Biovalves) 23 under high-pressure systemic flow. As shown in Figure 3, the wall of the Bio stent graft produced in this study exhibited approximately 80% of the tensile strength displayed by a Biotube of the same diameter.…”

Implantation study of a tissue-engineered self-expanding aortic stent graft (bio stent graft) in a beagle model

“…Regarding the durability of in vivo tissue-engineered cardiovascular materials, Watanabe et al [17] described the thickness and tensile strength of an in-body tissue-engineered graft (biotube) b Fig. 3 Circumferential cross sections of a BSG stained with hematoxylin-eosin (a), Masson-Trichrome (b), and Elastica van Gieson (c).…”