Autologous small-caliber "biotube" vascular grafts with argatroban loading: a histomorphological examination after implantation to rabbits

Functional autologous tubular tissues, termed "biotubes," have been developed as small-caliber vascular grafts. Biotubes can be easily and safely constructed in vivo by using a novel concept in regenerative medicine-in body tissue architecture technology, which requires neither clean specialized laboratories nor complex cell management. Biotubes with "anastomotic reinforcement cuffs" were prepared by embedding a silicone rod (diameter, 3 mm; length, 30 mm) as a mold in the dorsal subcutaneous pouches of rabbits. The rod was covered at both ends with 2 pieces of polyurethane sponge tubes (length, 3 mm), and it was removed when the grafts were harvested. These biotubes had homogeneous thin connective tissue walls (thickness: 76 +/- 37 microm) that were primarily composed of collagen and fibroblasts. The resulting cuff-impregnated biotubes were auto-implanted in the carotid arteries for predetermined periods of up to 12 weeks and then morphologically examined. On implantation of the biotubes after argatroban loading, the total patency was 9/11 without any instance of aneurysm formation or rupture. At 12 weeks after implantation, no significant neointimal thickening was observed (170 +/- 30 microm). In addition, minimal thrombus formation was observed on the luminal surfaces, which were completely covered with endothelial cells regularly oriented longitudinally. The regenerated vascular walls comprised multilayered smooth muscle cells and dense collagen fibers with regular circumferential orientation with few elastin fibers and were similar to native arteries. Biotubes with argatroban loading could thus be used as small-caliber vascular prostheses that greatly facilitate healing process and exhibit excellent biocompatibility.