In vitro maturation of “biotube” vascular grafts induced by a 2‐day pulsatile flow loading

Abstract

Autologous vascular tissues with a small diameter, "biotubes," were developed in vivo using a novel concept in regenerative medicine, "in-body tissue architecture technology." The effect of pulsatile flow in vitro was investigated on the structural and functional properties of the biotubes. Silicone rods (diameter, 3.0 mm; length, 35.0 mm), used as molds, were embedded into dorsal subcutaneous spaces of Wister rats. After 4 weeks, the autologous tubular tissues formed around the rods were harvested. Some tissues were incubated for 2 days under pulsatile flow simulating conditions in the human arteries with small caliber (wall shear stress (WSS), 15.5-77.3 dyn/cm(2); circumferential stress (CS), 0.6-4.5 x 10(5) dyn/cm(2)). Upon flow loading, the sparse, randomly oriented collagen fibers in the biotubes became dense and oriented in the regular circumferential direction. Compliances (beta values) of the control (ca. 30) and flow-loaded (ca. 20) biotubes were equivalent to that of the human coronary arteries and femoral arteries, respectively. Further, upon flow loading, the burst pressure significantly increased from ca. 1000 mmHg to ca. 1800 mmHg, along with the alpha-SMA-positive cell ratio. Pulsatile flow loading in vitro for 2 days could induce biotube maturation in terms of collagen structures and mechanical properties.