Genia Dubrovsky

A Wireless Implant for Gastrointestinal Motility Disorders

Implantable functional electrical stimulation (IFES) has demonstrated its effectiveness as an alternative treatment option for diseases incurable pharmaceutically (e.g., retinal prosthesis, cochlear implant, spinal cord implant for pain relief). However, the development of IFES for gastrointestinal (GI) tract modulation is still limited due to the poorly understood GI neural network (gut–brain axis) and the fundamental difference among activating/monitoring smooth muscles, skeletal muscles and neurons. This inevitably imposes different design specifications for GI implants. This paper thus addresses the design requirements for an implant to treat GI dysmotility and presents a miniaturized wireless implant capable of modulating and recording GI motility. This implant incorporates a custom-made system-on-a-chip (SoC) and a heterogeneous system-in-a-package (SiP) for device miniaturization and integration. An in vivo experiment using both rodent and porcine models is further conducted to validate the effectiveness of the implant.

Interstitial Matrix Prevents Therapeutic Ultrasound From Causing Inertial Cavitation in Tumescent Subcutaneous Tissue

We search for cavitation in tumescent subcutaneous tissue of a live pig under application of pulsed, 1-MHz ultrasound at 8 W cm-2 spatial peak and pulse-averaged intensity. We find no evidence of broadband acoustic emission indicative of inertial cavitation. These acoustic parameters are representative of those used in external-ultrasound-assisted lipoplasty and in physical therapy and our null result brings into question the role of cavitation in those applications. A comparison of broadband acoustic emission from a suspension of ultrasound contrast agent in bulk water with a suspension injected subcutaneously indicates that the interstitial matrix suppresses cavitation and provides an additional mechanism behind the apparent lack of in-vivo cavitation to supplement the absence of nuclei explanation offered in the literature. We also find a short-lived cavitation signal in normal, non-tumesced tissue that disappears after the first pulse, consistent with cavitation nuclei depletion in vivo.

Double plication for spring-mediated in-continuity intestinal lengthening in a porcine model

Background: Short bowel syndrome is a condition with substantial morbidity and mortality, yet definitive therapies are lacking. Distraction enterogenesis uses mechanical force to “grow” new intestine. In this study, we examined whether intestinal plication can be used to safely achieve spring‐mediated intestinal lengthening in a functioning segment of jejunum in its native position. Methods: A total of 12 juvenile, miniature Yucatan pigs underwent laparotomy to place either compressed springs or expanded springs within a segment of jejunum (n = 6 per group). The springs were secured within the jejunum by performing intestinal plication to narrow the intestinal lumen around the spring. After 3 weeks, the jejunum was retrieved and examined for lengthening and for histologic changes. Results: There were no intraoperative or postoperative complications, and the pigs tolerated their diets and gained weight. Segments of jejunum containing expanded springs showed no significant change in length over the 3 weeks. In contrast, jejunum containing compressed springs showed nearly a 3‐fold increase in length (P < .001). Histology of the retrieved jejunum showed a significant increase in thickness of the muscularis propria and in crypt depth relative to normal jejunum. Conclusion: Intestinal plication is effective in securing endoluminal springs to lengthen the jejunum. This approach is a clinically relevant model because it allows for normal GI function and growth of animals during intestinal lengthening, which may be useful in lengthening intestine in patients with short bowel syndrome.

Three-dimensionally printed surface features to anchor endoluminal spring for distraction enterogenesis

Spring-mediated distraction enterogenesis has been studied as a novel treatment for short bowel syndrome (SBS). Previous approaches are limited by multiple surgeries to restore intestinal continuity. Purely endoluminal devices require a period of intestinal attachment for enterogenesis. The purpose of this study is to modify the device to prevent premature spring migration in a porcine model. Two models were created in juvenile mini-Yucatan pigs for the placement of three-dimensionally printed springs. (1) Two Roux-en-y jejunojenostomies with two Roux limbs were made. A spring with bidirectional hooked surface features was placed in one Roux limb and a spring with smooth surface was placed in the other Roux limb. (2) The in-continuity model had both hooked and smooth surface springs placed directly in intestinal continuity. Spring location was evaluated by weekly radiographs, and the intestine was retrieved after 2 to 4 weeks. Springs with smooth surfaces migrated between 1 to 3 weeks after placement in both porcine models. Springs with bidirectional hooked surface features were anchored to the intestine for up to 4 weeks without migration. Histologically, the jejunal architecture showed significantly increased crypt depth and muscularis thickness compared to normal jejunum. Bidirectional features printed on springs prevented the premature migration of endoluminal springs. These novel spring anchors allowed for their endoluminal placement without any sutures. This approach may lead to the endoscopic placement of the device for patients with SBS.

Intestinal lengthening via multiple in-continuity springs

BACKGROUND 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. METHODS 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. RESULTS 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). CONCLUSIONS 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.

Double plication for spring-mediated intestinal lengthening of a defunctionalized Roux limb

BACKGROUND 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. METHODS 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. RESULTS 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. CONCLUSIONS 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 OF EVIDENCE Level I Experimental Study.