Development of an endoluminal intestinal lengthening device using a geometric intestinal attachment approach

Abstract

Background Distraction enterogenesis may provide a novel therapy for short bowel syndrome. Previously described methods have relied on isolated intestinal segments or transmural fixation due to ineffective endoluminal attachment. We hypothesized that a novel approach using geometric coupling between a tapering device and the mesenteric curvature would allow transstomal distraction enterogenesis. Methods A catheter device was designed with tapering stiffness, consisting of a stiff catheter with a taper to a flexible latex tip to prevent perforation. Yorkshire pigs underwent creation of a jejunal Roux limb with device placed via jejunostomy. Intestinal attachment was achieved without a substantial decrease in bowel perfusion as measured by laser Doppler. An external clamp was secured at the stoma to provide external fixation of the device. The catheter was advanced 1 cm/day for either 7 or 14 days before explant. Results After 7 days, the distracted segment achieved a mean±SD increase in length of 37±6% versus fed, nondistracted bowel, corresponding to an absolute gain of 10.6±1.7 cm (1.5 cm/day). After 14 days, the Roux limb achieved an 80±2% increase in length versus fed control bowel, corresponding to an absolute gain of 16.8±3.0 cm (1.2 cm/day). No perforation or stoma-related complication occurred. Conclusion We describe a novel catheter device with tapering stiffness allowing for endoluminal distraction enterogenesis via geometric coupling. This approach may allow development of clinically applicable technology for the treatment of patients with short bowel syndrome.

Mechanically induced development and maturation of human intestinal organoids in vivo

“…Our use of the spring was based upon previous studies describing endoluminal lengthening devices 14 – 17 , 20 . We found the nickel-titanium (nitinol, NiTi) spring as an ideal device, because it had been successfully used in rats and did not require manipulation post implantation as hydraulic devices do 14 , 17 . Another advantage in utilizing the NiTi spring is that a large amount of negative space was retained within the tHIO after insertion, which permitted mucous accumulation.…”

“…Much like other endoluminal lengthening devices, the spring has been shown to stimulate an adaptive morphometric response in the setting of mature tissues, though additional effects have not been thoroughly characterized 14 – 18 . Of the various lengthening devices previously described, we chose to utilize the spring because its geometry and applied force could be scaled for our purposes and it allows for the accumulation of mucous as the tHIO is a closed system 14 – 17 . In combining these transplantation strategies, we hypothesized that the application of strain in a fetal setting would elicit tissue maturation and overall growth of the tHIO.…”

Expanding intestinal segment using osmotic hydrogel: An in vivo study

“…Recently, a variety of devices and operative approaches have been tested in animals for the treatment of SBS, but none of these approaches have been translated into clinical practice thus far. Self‐expanding, shape‐memory polymer cylinder, catheter device and a telescopic hydraulic device have all been tested, but their translations seem to be limited by the need for complex activation mechanisms or the surgical risks associated. These devices appeared challenging to use in a clinical scenario because of reported discomfort, pain and complications …”

Biologically inspired approaches to enhance human organoid complexity

“…A more recent approach to generate scalable, mature intestinal tissue from HIOs incorporated mechanical strain using lengthening springs ( Poling et al, 2018 ). Mechanical strain has been shown to play a role in intestinal development ( Kurpios et al, 2008 ; Savin et al, 2011 ; Shyer et al, 2015 , 2013 ), and spring or stretch-based lengthening devices have been designed as treatment methods for short bowel syndrome ( Demehri et al, 2015 , 2014 ; Ralls et al, 2012 ; Rouch et al, 2016 ; Stark et al, 2012 ; Sueyoshi et al, 2013 ). In this approach, HIOs were transplanted into immunocompromised mice for 10 weeks.…”