Development of an In-body-tissue-engineered Collagenous Biosheet for Regenerative Vascular Reconstruction in a Beagle Model

Abstract

Introduction - Autologous pericardial tissues are commonly used for the arterial reconstruction. To overcome their limited amount, tissue-engineered material that has potential to engraft to native tissues and then grow is desired especially in pediatric surgery. In body tissue architecture (iBTA) can prepare autologous collagenous sheet-like tissues, called Biosheets, by using a patient's body as a bioreactor. Its process is simple and safe, just subcutaneously embedding a mold for about 2 months. Since Biosheet has sufficient mechanical properties they could be applied as reconstruction materials for abdominal wall or diaphragm. This study investigated the possibility of Biosheet as a regenerative vascular reconstruction material in a beagle model. Methods - Cylindrical molds (diameter 18 mm, length 7 cm) were embedded in beagles or cows (Hokkaido University) subcutaneously for 2 months. Tubular tissues were formed inside of all molds, and were harvested upon removing the mold. Canine or bovine Biosheets (size 5 x 7 cm, thickness ca. 0.6 mm) were obtained by cutting the tubular tissues at the longitudinal direction as collagenous sheet-like tissues. Arterial defects at pulmonary arteries (ca. 10 × 20 mm, 1 in photos) or descending aorta (ca. 10 x 10 mm, 2 in photos) were made and patch repair using Biosheets was performed in beagles under partial clamping. Results - In ultrasonic echo observation, little change in blood flow change occurred after the patching. Angiogram showed no elongation or stenosis at the patched region (3 in photos). Tissue migration from native artery occurred primarily on the luminal surface of the Biosheets with their degradation (4 in photos). Even in xeno implantation using bovine Biosheets after 6 months Bioisheets were almost completely disappeared and partial arterial reconstruction was observed. The function as a pulmonary or aortic artery was maintained for more than 6 months. Conclusion - Biosheet could function as a regenerative vascular repair material even at arteries or in xeno grafts.