Spring Mediated Enterogenesis

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Project Summary Lengthening the small intestine is a potentially curative therapy for patients with intestinal failure due to short bowel syndrome. Short bowel syndrome is the end result of devastating diseases that affect the small intestine. Patients with short bowel syndrome have malabsorption and cannot eat normal meals. The current therapy for short bowel syndrome consists of providing parenteral nutrition, optimizing the health of the remnant intestine, and enhancing intestinal adaptation. While parenteral nutrition has dramatically improved their survival, many patients with short bowel syndrome cannot be weaned from parenteral nutrition and develop end stage liver disease. Over the last decade, we developed and refined devices to lengthen the small intestine. By applying a gradual force to a segment of the small intestine separated from continuity, we were able to triple the length of the small intestine in rats and pigs. There was a net growth of the intestinal cell mass and an increase in the absorptive surface area. The lengthened segment was functional when it was restored back into intestinal continuity. These studies demonstrated the potential of mechanical intestinal lengthening as a novel treatment of patients with short bowel syndrome. In this proposed research, we will obtain data on spring devices that will lengthen the intestine that are still in intestinal continuity in different size animals. We will also develop ways to maximize intestinal lengthening with multiple springs applied repeatedly. Lastly, we will employ the spring in a porcine short bowel model. If successful, these studies will lead to a Phase 1 clinical trial of these devices in patients with short bowel syndrome. This approach will revolutionize the treatment strategy of patients with short bowel syndrome.