SUCCESSFUL ANASTOMOSIS BETWEEN TISSUE-ENGINEERED INTESTINE AND NATIVE SMALL BOWEL

Abstract

102 Purpose: Previous work from this laboratory reported that isolated intestinal epithelial organoid units on biodegradable polymer scaffolds formed cysts lined by a neomucosa. The purpose of this study was to demonstrate the possibility of anastomosing tissue-engineered intestine to the native small bowel and to see the effect of this anastomosis on cyst growth. Materials and Methods: Microporous biodegradable polymer tubes were created from a fiber mesh of polyglycolic acid and sprayed on the outer surface with 5% polylactic acid. Intestinal epithelial organoid units were harvested from 7 day old Lewis rats and seeded onto polymers at a density of 7.9-9.0 × 104 units/polymer. These unit-polymer constructs were implanted into the abdominal cavity of adult male Lewis rats (n=38) wrapped with omentum. Three weeks from initial operation, the unit-polymer constructs, which formed cysts lined by a thin neomucosa, were anastomosed in a side-to-side fashion to the native jejunum in 20 rats with interrupted suture using 6-0 silk (Group 1). The other 18 rats were closed without anastomosis (Group 2). All rats were sacrificed 10 weeks after implantation and the tissue-engineered constructs were harvested. Assessment: (1) body weight change, (2) upper GI study before sacrifice, (3) cyst size at second operation and sacrifice, (4) histological findings of cyst and anastomosis. Results: All rats survived this study. Rats in Group 1 increased their body weights equal to those in Group 2 and there was no statistically significant difference between the 2 groups at the time of sacrifice (Group 1; 394.4±29.9g, Group 2; 400.3±28.5g). Upper GI revealed no evidence of either bowel stenosis or obstruction at the anastomotic site. The patency of the anastomosis was 90% (18 of 20 rats) and in some cases, the lumen of the cyst was visualized by the upper GI study. At the second operation, there was no significant difference in the size of the cysts in either groups, however, the length of the cysts in Group 1 was significantly longer than that of Group 2 at the time of sacrifice (Group 1; 15.0±4.3mm, Group 2; 13.0±1.7mm, p<0.05 by Mann-Whitney's U test). Histology showed that cysts after anastomosis were lined by a neomucosal layer characterized by crypt-villus structures and had continuity to native mucosa. Conclusion: (1) Anastomosis between tissue-engineered intestine and native small bowel has no complications after operation. (2) The anastomosis keeps a high patency rate and there is a continuity in tissue-engineered intestine and native small bowel on histology. (3) Anastomosis has a good effect on cyst size and development of mucosa in the tissue-engineered intestine.