nitinol and Short-Bowel-Syndrome

Short bowel syndrome is a devastating gastrointestinal disorder in which decreased bowel length results in inadequate absorption causing nutritional deficiencies. Current treatment options are accompanied by significant morbidity. We have proposed spring-mediated distraction enterogenesis as a method to lengthen bowel with success seen in porcine jejunum. We hypothesize that spring-mediated distraction enterogenesis can be demonstrated in porcine ileum with preservation of ileal structure and function.. Laparotomy was performed on juvenile female mini-Yucatan pigs and a gelatin-encapsulated compressed nitinol spring was inserted into the ileal lumen and affixed proximally and distally. A control segment distal to the spring segment was marked with sutures. Postoperatively, pigs were placed on a liquid diet and euthanized on postoperative day 7. Spring and control segments were measured and processed for immunohistochemistry to evaluate for the presence of vitamin B12-intrinsic factor cotransporter, chromogranin A-producing cells, and 5-HT producing cells.. All seven pigs survived to postoperative day 7 with no adverse effects. On average, pigs gained 84.3 ± 66.4 g/d. Spring segments lengthened 1.5 ± 0.7 cm with a relative lengthening by 128% ± 56%, which was statistically significant when compared to control (P < 0.01). The average density of chromogranin-A cells in control compared to spring segments was not significantly changed (2.9 ± 1.1 cells/mm versus 3.2 ± 1.2 cells/mm, P = 0.17). Both vitamin B12-intrinsic factor cotransporter and 5-HT producing cells were present in both control and lengthened ileum.. Intraluminal nitinol springs significantly lengthened porcine ileum. The increase in density of enteroendocrine cells may indicate enhanced endocrine function of the lengthened ileum.

Topics: Animals; Chromogranin A; Chromogranins; Female; Gelatin; Ileum; Intrinsic Factor; Jejunum; Serotonin; Short Bowel Syndrome; Swine; Swine, Miniature; Tissue Expansion; Tissue Expansion Devices; Vitamin B 12

Short bowel syndrome is a debilitating condition with few effective treatments. Spring-mediated distraction enterogenesis can be used to lengthen intestine. The purpose of this study is to determine whether multiple springs in series can safely increase the total amount of lengthening.. Juvenile mini-Yucatan pigs each received three nitinol springs placed within their jejunum. Plication was used to narrow the intestine around each spring to secure them. Compressed springs were used in the experimental group, while uncompressed springs were used in the control group. The intestine was examined 3 weeks later for lengthening and histologic changes.. All pigs tolerated diets postoperatively with continued weight gain, and no dilation or obstruction of the intestine was observed. Segments of intestine that contained compressed springs had a significant increase in length from 2.5 cm to 3.9 ± 0.2 cm per spring, compared to segments containing control springs that showed no change (p < 0.001).. Intestinal plication can be safely used to secure multiple springs in series to achieve intestinal lengthening without compromising intestinal function. Using several springs at once allows for a greater amount of total lengthening. This is a promising model that has potential in the treatment of short bowel syndrome.

Topics: Alloys; Animals; Digestive System Surgical Procedures; Intestines; Short Bowel Syndrome; Swine; Tissue Expansion Devices

Spring-mediated distraction enterogenesis has been shown to increase the length of an intestinal segment. The goal of this study is to use suture plication to confine a spring within an intestinal segment while maintaining luminal patency to the rest of the intestine.. Juvenile mini-Yucatan pigs underwent placement of nitinol springs within a defunctionalized Roux limb of jejunum. A 20 French catheter was passed temporarily, and sutures were used to plicate the intestinal wall around the catheter at both ends of the encapsulated spring. Uncompressed springs placed in plicated segments and springs placed in nonplicated segments served as controls. The intestine was examined approximately 3 weeks after spring placement.. In the absence of plication, springs passed through the intestine within a week. Double plication allowed the spring to stay within the Roux limb for 3 weeks. Compared to uncompressed springs that showed no change in the length of plicated segments, compressed springs caused a significant 1.7-fold increase in the length of plicated segments.. Intestinal plication is an effective method to confine endoluminal springs. The confined springs could lengthen intestine that maintains luminal patency. This approach may be useful to lengthen intestine in patients with short bowel syndrome.. Level I Experimental Study.

Topics: Alloys; Animals; Catheters; Digestive System Surgical Procedures; Female; Jejunum; Models, Animal; Short Bowel Syndrome; Swine; Swine, Miniature; Tissue Expansion; Tissue Expansion Devices

Distraction enterogenesis has been investigated as a novel treatment for short bowel syndrome (SBS). With variable intestinal sizes, it is critical to determine safe, translatable spring characteristics in differently sized animal models before clinical use. Nitinol springs have been shown to lengthen intestines in rats and pigs. Here, we show spring-mediated intestinal lengthening is scalable and feasible in a murine model.. A 10-mm nitinol spring was compressed to 3 mm and placed in a 5-mm intestinal segment isolated from continuity in mice. A noncompressed spring placed in a similar fashion served as a control. Spring parameters were proportionally extrapolated from previous spring parameters to accommodate the smaller size of murine intestines. After 2-3 wk, the intestinal segments were examined for size and histology.. Experimental group with spring constants, k = 0.2-1.4 N/m, showed intestinal lengthening from 5.0 ± 0.6 mm to 9.5 ± 0.8 mm (P < 0.0001), whereas control segments lengthened from 5.3 ± 0.5 mm to 6.4 ± 1.0 mm (P < 0.02). Diameter increased similarly in both groups. Isolated segment perforation was noted when k ≥ 0.8 N/m. Histologically, lengthened segments had increased muscularis thickness and crypt depth in comparison to normal intestine.. Nitinol springs with k ≤ 0.4 N/m can safely yield nearly 2-fold distraction enterogenesis in length and diameter in a scalable mouse model. Not only does this study derive the safe ranges and translatable spring characteristics in a scalable murine model for patients with short bowel syndrome, it also demonstrates the feasibility of spring-mediated intestinal lengthening in a mouse, which can be used to study underlying mechanisms in the future.

Topics: Alloys; Animals; Feasibility Studies; Mice; Mice, Inbred C57BL; Short Bowel Syndrome; Tissue Expansion; Tissue Expansion Devices; Treatment Outcome

Prior studies demonstrated the feasibility of lengthening intestinal segments with mechanical force, but no previous studies have restored the lengthened segment back into intestinal continuity.. A 1-cm segment of isolated rat jejunum was lengthened using a Nitinol spring. After lengthening, this segment was restored into intestinal continuity via a transection of the intact small intestine. Rats were euthanized 2 weeks later to retrieve the restored intestinal segment for histologic and enzymatic analyses.. The isolated jejunal segments were initially lengthened to 3.3 ± 0.9 cm. After the lengthened segments were restored into intestinal continuity for 2 weeks, the final length of the restored segment was 1.9 ± 0.7 cm. All rats continued to gain weight, and the intestine proximal to the restored jejunal segment remained normal 2 weeks later. The restored jejunal segment had an increase in crypt depth and no difference in villus height compared with normal jejunum. Sucrase activity in the restored segment was not different from that in normal jejunum.. Mechanically lengthened jejunum can be restored into intestinal continuity and appears to have normal function. This further demonstrates the feasibility of mechanical enterogenesis as a potential therapy for short bowel syndrome.

Topics: Alloys; Anastomosis, Surgical; Animals; Capsules; Cellulose; Coated Materials, Biocompatible; Disease Models, Animal; Equipment Design; Female; Implants, Experimental; Intestinal Mucosa; Jejunum; Microvilli; Organ Size; Polyethylene; Rats; Rats, Sprague-Dawley; Short Bowel Syndrome; Stress, Mechanical; Sucrase; Tissue Expansion; Tissue Expansion Devices; Weight Gain

Prior studies demonstrating the ability to lengthen intestinal segments with mechanical force required devices with extracorporeal components. The feasibility of using a completely implantable device for in vivo intestinal lengthening was evaluated in this study.. Biocompatible Nitinol springs capable of 5-fold expansions were compressed using absorbable sutures and were implanted into isolated segments of proximal jejunum in rats. Springs compressed with nonabsorbable sutures served as controls. The animals were observed with serial abdominal x-rays until the springs became fully expanded. Intestinal segments were then retrieved for histologic analysis. Two-tailed and paired Student's t tests were used for statistical analysis.. Intestinal segments were successfully lengthened in the experimental group from 1.3 +/- 0.3 cm to 4.4 +/- 0.5 cm (P < .001). Maximum spring length was achieved on postoperative day 36 (range, 16-50 days). In the control group, there was also an increase in intestinal lengths, from 1.6 +/- 0.04 cm to 2.9 +/- 0.4 cm (P < .001) (Fig. 4). In percentages, a 250% increase in length was observed in the experimental group vs an 85% increase in the control group (P < .001). Microscopic evaluation of both control and experimental segments revealed gross preservation of intestinal architecture; however, muscular layer hypertrophy and villous atrophy were noted.. Continuous mechanical force with an implantable spring successfully lengthened isolated segments of small bowel in an animal model. Although similar results have been demonstrated using other devices, the current device is totally implantable and may be deployed endoscopically.

Topics: Alloys; Animals; Digestive System Surgical Procedures; Endoscopy, Gastrointestinal; Feasibility Studies; Jejunum; Models, Animal; Prostheses and Implants; Rats; Short Bowel Syndrome; Stents; Tissue Expansion; Tissue Expansion Devices