Generation of Porcine Ileum Through Spring-mediated Mechanical Distraction

Background: Short bowel syndrome is a devastating gastrointestinal disorder in which nutritional deficiencies occur due to inadequate absorption. Current treatment options have significant morbidities therefore we previously proposed spring-mediated distraction enterogenesis as a method to lengthen bowel with success seen in porcine jejunum. Our current hypothesis is that spring-mediated distraction enterogenesis can be demonstrated in porcine ileum with preservation of structure and function.

Methods: Laparotomy was performed on juvenile female mini-Yucatan pigs where a gelatin-encapsulated compressed nitinol spring was inserted into the lumen of the ileum and plicated proximally and distally. Control segments were marked with sutures. Post-operatively, pigs were placed on liquid diet and euthanized on post-operative day (POD) 7. Spring and control segments were measured. Ileum segments were formalin-fixed, paraffin-embedded, and stained by immunohistochemistry against enteroendocrine protein Chromogranin-A. The density of chromogranin-A positive cells was calculated.

Results: Eight pigs received ileal springs. Spring constants ranged 4.6-6.5 N/m. All pigs survived to POD7 with no adverse effects. On average, pigs gained 79.3士 59.2 grams/day. Spring segments significantly lengthened 2.0士1.5cm with a relative change of 227%士48% increase (p < 0.001). The average density of chromogranin-A cells in control compared to spring segments was not statistically significant (2.4±1.2cells/mm vs. 3.0±1.1cell/mm, p>0.05).

Conclusion: Intraluminal nitinol springs significantly lengthen porcine ileum. Mechanotransduction triggered new cell division in every microscopic layer. While the density of enteroendocrine cells is similar between control and spring segments, given the lengthening seen, the number of cells overall is increased and the function should be similar.