Intestinal Electrical Stimulation to Increase the Rate of Peristalsis.

BACKGROUND: Pediatric gastrointestinal motility disorders are a large and broad group. Some of these disorders have been effectively treated with electrical stimulation. The goal of our present study is to determine whether the rate of intestinal peristalsis can be increased with electrical stimulation. METHODS: Juvenile mini-Yucatan pigs were placed under general anesthesia and a short segment of the jejunum was transected. Ultrasound gel was placed inside the segment. The segment of the jejunum was first monitored for 20 min under no stimulation, followed by direct electrical stimulation using a planar electrode. The gel extruded out of the intestine via peristalsis was collected and weighed for each 20-min time interval. RESULTS: Effective delivery of the current to the intestine was confirmed via direct measurements. When there was no direct intestinal electrical stimulation, an average of 0.40 g of gel was expelled in 20 min, compared to 1.57 g of gel expelled during direct electrical stimulation (P < 0.01). CONCLUSIONS: Direct intestinal electrical stimulation accelerates the transit of gastrointestinal contents. This approach may be useful in the treatment of a range of pediatric motility disorders.

Subcutaneous cefazolin to reduce surgical site infections in a porcine model.

BACKGROUND: Surgical site infections (SSIs) pose a significant health and financial burden. A key aspect of appropriate prophylaxis is the administration of antibiotics intravenously (IV). However, subcutaneous administration of antibiotics is not well described in the literature. During surgery, we hypothesize that subcutaneous injection may provide better protection against SSIs. To better understand the kinetics after subcutaneous injection, we describe the serum concentrations of cefazolin in a porcine model. MATERIALS AND METHODS: Juvenile mini-Yucatan pigs were administered 20 mL of 25 mg/kg cefazolin subcutaneously, and serial blood samples were taken for 3 h. Blood samples were analyzed for cefazolin concentration using chromatography. Pharmacokinetic data were calculated based on the blood serum concentrations. RESULTS: Maximum serum concentrations of cefazolin were achieved 42.6 ± 2.0 min after the time of injection and were found to be 18.8 ± 7.4 µg/mL. The elimination rate constant was 0.0033 ± 0.0016 min-1 and the half-life was 266 ± 149 min. The area under the curve was 4940 ± 1030 µg × min/mL. The relative bioavailability of subcutaneous injection was 95% +5%/-20%. CONCLUSIONS: Subcutaneous administration of cefazolin achieves a significantly lower maximum serum concentration than IV injection. As a result, higher doses of antibiotic can be injected locally without incurring systemic toxicity. Subcutaneous administration will therefore result in higher concentrations of antibiotic for a longer time at the incision site compared with standard IV administration. This strategy of antibiotic delivery may be more effective in preventing SSIs. Further studies are needed to detail the exact effect of subcutaneous antibiotic injection on SSI rates.

Mechanisms for intestinal regeneration.

PURPOSE OF REVIEW: The purpose of this review is to briefly summarize the notable structures and pathways in intestinal epithelial growth before presenting the current main areas of active research in intestinal regeneration. As a rapidly advancing field, a number of breakthroughs have recently been made related to the culture of intestinal stem cells (ISCs) and to the engineering of intestinal tissue. RECENT FINDINGS: ISCs can be derived from fibroblasts and can be cultured in hydrogels under xenogeneic-free conditions. Intestinal organoids can be cultured with neural crest cells to form small intestinal tissues with neuromuscular networks. Endoluminal devices can be placed inside the native intestine to exert mechanical force to induce novel tissue growth. SUMMARY: A number of recent advances in the field of intestinal regeneration are encouraging and suggest that novel therapies for a wide range of intestinal disorders may be developed in the near future. There are still a number of obstacles before such stem cell therapies can be safely used in humans.

Clinical and socioeconomic factors associated with negative pediatric appendicitis.

BACKGROUND: Misdiagnosing appendicitis may lead to unnecessary surgery. The study evaluates the risk factors for negative appendectomies, as well as the clinical and socioeconomic consequences of negative appendectomy across three states. MATERIALS AND METHODS: Data were obtained from the California, New York, and Florida State Inpatient Databases 2005-2011. Patients (<18 years) who underwent nonincidental appendectomies (n = 156,660) were evaluated with hierarchical and multivariate negative binomial regression analyses on outcomes including hospital cost, length of stay (LOS), and associated morbidity. RESULTS: From 2005 to 2011, there was a decrease in the rate of negative appendicitis and perforated appendicitis, whereas the rate of true acute nonperforated appendicitis increased. Whites, females, and privately insured patients were associated with higher negative appendicitis rates, whereas those at an increased risk for perforated appendicitis were African-Americans, males, and those with public or no insurance. Compared to patients with acute nonperforated appendicitis, those with negative appendicitis have significantly higher morbidity (2.5% versus 1.3%), longer LOS (3.4 versus 1.8 d), and greater hospital costs averaged over time ($6926 versus $6492 per patient). CONCLUSIONS: Despite a low incidence, negative appendicitis is associated with greater morbidity, longer LOS, and higher cost than acute nonperforated appendicitis. Certain subpopulations are at higher risk for undergoing surgery for negative appendicitis, whereas others are at greater risk for presenting with perforated appendicitis. Further research is needed to understand what drives such disparities and to inform efforts to improve quality of hospital care across all groups of patients.

Feasibility and scalability of spring parameters in distraction enterogenesis in a murine model.

BACKGROUND: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Spring-mediated distraction enterogenesis may alter the course of adaptation in porcine short bowel syndrome.

Introduction: Severe forms of short bowel syndrome (SBS) resulting in chronic intestinal failure (IF) have limited therapeutic options, all of which are associated with significant morbidities. Spring-mediated distraction enterogenesis (SMDE) uses an intraluminal self-expanding spring to generate mechanical force to induce intestinal stretching and sustained axial growth, providing a promising novel approach for patients with SBS. Previous studies have established this method to be safe and effective in small and large animal models. However, SMDE has previously not been implemented in a large, clinically relevant animal model. Methods: Juvenile mini-Yucatan pigs with 75% of their small intestine resected had intraluminal springs placed after an initial adaptive period. Morphological and histological assessments were performed on SMDE segments compared to the control region of the intestine undergoing normal adaptive responses to resection. Results: While the initial histologic adaptive response observed following resection was attenuated after a month, the SMDE segments instead augmented these adaptive changes. Specifically, intestinal length increased 2-fold in SMDE segments, and the widths of the epithelial, muscularis, and serosal layers were enhanced in SMDE compared with control segments of the same animal. This data suggests that morphologic intestinal adaptation may be enhanced with SMDE in the setting of SBS. Discussion: Here we demonstrate the successful and reproducible implementation of SMDE in a large animal model in the setting of prior intestinal resection, making SMDE a viable and novel approach for SBS to be explored further.

DNA variations in oculocutaneous albinism: an updated mutation list and current outstanding issues in molecular diagnostics.

Oculocutaneous albinism (OCA) is a rare genetic disorder of melanin synthesis that results in hypopigmented hair, skin, and eyes. There are four types of OCA caused by mutations in TYR (OCA-1), OCA2 (OCA-2), TYRP1 (OCA-3), or SLC45A2 (OCA-4). Here we report 22 novel mutations in the OCA genes; 14 from a cohort of 61 patients seen as part of the NIH OCA Natural History Study and eight from a prior study at the University of Minnesota. We also include a comprehensive list of almost 600 previously reported OCA mutations along with ethnicity information, carrier frequencies, and in silico pathogenicity predictions as a supplement. In addition to discussing the clinical and molecular features of OCA, we address the cases of apparent missing heritability. In our cohort, 26% of patients did not have two mutations in a single OCA gene. We demonstrate the utility of multiple detection methods to reveal mutations missed by Sanger sequencing. Finally, we review the TYR p.R402Q temperature-sensitive variant and confirm its association with cases of albinism with only one identifiable TYR mutation.

Deletion of the Cel48S cellulase from Clostridium thermocellum.

Clostridium thermocellum is a thermophilic anaerobic bacterium that rapidly solubilizes cellulose with the aid of a multienzyme cellulosome complex. Creation of knockout mutants for Cel48S (also known as CelS, S(S), and S8), the most abundant cellulosome subunit, was undertaken to gain insight into its role in enzymatic and microbial cellulose solubilization. Cultures of the Cel48S deletion mutant (S mutant) were able to completely solubilize 10 g/L crystalline cellulose. The cellulose hydrolysis rate of the S mutant strain was 60% lower than the parent strain, with the S mutant strain also exhibiting a 40% reduction in cell yield. The cellulosome produced by the S mutant strain was purified by affinity digestion, characterized enzymatically, and found to have a 35% lower specific activity on Avicel. The composition of the purified cellulosome was analyzed by tandem mass spectrometry with APEX quantification and no significant changes in abundance were observed in any of the major (>1% of cellulosomal protein) enzymatic subunits. Although most cellulolytic bacteria have one family 48 cellulase, C. thermocellum has two, Cel48S and Cel48Y. Cellulose solubilization by a Cel48S and Cel48Y double knockout was essentially the same as that of the Cel48S single knockout. Our results indicate that solubilization of crystalline cellulose by C. thermocellum can proceed to completion without expression of a family 48 cellulase.

Parental attitudes towards choosing between operative and nonoperative management of pediatric acute appendicitis.

INTRODUCTION: Making healthcare decisions for children can be challenging for parents or guardians. We aimed to characterize the decision-making preferences and stress of parents or guardians who were offered both appendectomy or nonoperative management (NOM) for children with acute appendicitis. METHODS: Criteria was developed for offering operative or NOM for patients. At the time of decision, parents or guardians completed a survey assessing their understanding of treatment options, stress and preferences in being given the choice. An outpatient follow-up survey was later administered to evaluate post-decision satisfaction. RESULTS: A total of 45 respondents were included in the study. More than 95% endorsed understanding of the risks/benefits of the options and felt supported and satisfied with their decision. Half felt the process was more than minimally stressful, 77% felt the decision was easy to make, 89% liked being asked and 95% preferred to make the decision themselves with varying degrees of input from their physician. Of the 62% of parents or guardians who completed the follow-up survey, >90% were satisfied with their decision and one respondent regretted their choice. DISCUSSION: When offered the choice between operative and NOM of acute appendicitis, half of parents or guardians felt greater than minimal stress. The majority endorsed adequate understanding of the options, felt it was an easy decision, and maintained the desire to be the primary decision maker for their child. Our study provides preliminary data on parental or guardian attitudes towards shared decision-making in the surgical setting. Follow-up studies should focus on identifying predictors for those who feel increased stress and difficulty with decision-making. LEVEL OF EVIDENCE: III.

Management of a large delayed esophageal perforation in a fresh liver transplant patient with endoscopic placement of a nasopleural drainage tube-a case report.

Esophageal perforation in liver transplant recipients is a rare phenomenon. We herein report a case of an esophageal perforation due to Sengstaken-Blakemore tube in a liver-transplant recipient diagnosed 6 weeks post-transplant. A 2.5-cm mid-esophageal perforation communicating with large complex fluid collection in the pleural space was found. During endoscopy, 16Fr Salem Sump nasopleural tube (NP) was placed traversing through esophageal perforation into inferior aspect of the collection. Over the following 4 weeks, NP decompressed the cavity, allowed its closure and the tube was slowly retracted. By the end of 4 weeks, NP was removed with follow-up esophagogram showing no extravasation of contrast and a healed perforation. Hence, the esophageal perforation was successfully treated via this unique nonoperative approach without the need for major surgery. In instances of chronic leak with a stable patient, this nonoperative strategy should be considered even in immunocompromised patients.

Optimization of In-Continuity Spring-Mediated Intestinal Lengthening.

BACKGROUND: Spring-mediated intestinal lengthening has been studied in numerous animal models to effectively achieve up to a 3-fold increase in length. In this study we are interested in optimizing this method of spring lengthening. METHODS: Juvenile mini-Yucatan pigs underwent laparotomy for spring implantation. Springs were secured by plicating the intestine around the springs. In one set of experiments, varying degrees of plication were compared to determine the necessary narrowing needed to confine the spring. In another set of experiments, dissolvable sutures were used for the plication to allow for spontaneous spring passage postoperatively. Intestinal segments were retrieved and evaluated for lengthening and histological changes. RESULTS: Pigs tolerated their diet advancement to a regular diet postoperatively. 10% plication resulted in a 1.3-fold increase in length, while 50% plication resulted in a 2.7-fold increase in length (p<0.05). At two months postoperatively, the majority of springs had safely passed out of the intestine. All lengthened intestine showed significant growth histologically. CONCLUSIONS: A 50% reduction in lumen diameter achieves optimal spring-mediated intestinal lengthening. Springs can safely pass out of the intestine, thus avoiding a second operation for spring removal. These results may be important in developing future therapies for short bowel syndrome. LEVEL OF EVIDENCE: Level I experimental study.

Electroacupuncture to Increase Neuronal Stem Cell Growth.

Background: Neuropathic intestinal disorders continue to pose a significant burden, and current treatment options do not target the underlying cellular deficiencies. The goal of this study is to determine whether acupuncture and electroacupuncture (EA) can affect the growth of neuronal cells. Methods: Three groups of Lewis rats received 25 minutes of acupuncture twice a week for 10 weeks. The 3 groups of rats received treatment with either sham acupuncture (SA), real acupuncture (RA), or EA. After 10 weeks of treatment, skin and intestinal tissue were collected and analyzed for histology and mRNA expression of neuronal marker genes. Results: Compared with rats that received SA, rats that received RA and EA showed a significant increase in the mRNA expression levels of multiple neuronal genes in the skin. No significant histologic changes were seen. Conclusions: Acupuncture and EA result in significant changes in the expression of genes implicated as markers for neural stem cells, neural cell development, and neurons. This may, therefore, provide a novel avenue for developing treatments in patients suffering from intestinal aganglionic and neuropathic diseases.

Autologous Transplantation of Skin-Derived Precursor Cells in a Porcine Model.

BACKGROUND: Hirschprung's disease is characterized by aganglionic bowel and often requires surgical resection. Cell-based therapies have been investigated as potential alternatives to restore functioning neurons. Skin-derived precursor cells (SKPs) differentiate into neural and glial cells in vitro and generate ganglion-like structures in rodents. In this report, we aimed to translate this approach into a large animal model of aganglionosis using autologous transplantation of SKPs. METHODS: Juvenile pigs underwent skin procurement from the shoulder and simultaneous chemical denervation of an isolated colonic segment. Skin cells were cultured in neuroglial-selective medium and labeled with fluorescent dye for later identification. The cultured SKPs were then injected into the aganglionic segments of colon, and the specimens were retrieved within seven days after transplantation. SKPs in vitro and in vivo were assessed with histologic samples for various immunofluorescent markers of multipotency and differentiation. SKPs from the time of harvest were compared to those at the time of injection using PCR. RESULTS: Prior to transplantation, 72% of SKPs stained positive for nestin and S100b, markers of neural and glial precursor cells of neural crest origin, respectively. Markers of differentiated neurons and gliocytes, TUJ1 and GFAP, were detected in 47% of cultured SKPs. After transplantation, SKPs were identified in both myenteric and submucosal plexuses of the treated colon. Nestin co-expression was detected in the SKPs within the aganglionic colon in vivo. Injected SKPs appeared to migrate and express early neuroglial differentiation markers. CONCLUSIONS: Autologous SKPs implanted into aganglionic bowel demonstrated immunophenotypes of neuroglial progenitors. Our results suggest that autologous SKPs may be potentially useful for cell-based therapy for patients with enteric nervous system disorders. TYPE OF STUDY: Basic science.

The effect of colonic tissue electrical stimulation and celiac branch of the abdominal vagus nerve neuromodulation on colonic motility in anesthetized pigs.

BACKGROUND: Knowledge on optimal electrical stimulation (ES) modalities and region-specific functional effects of colonic neuromodulation is lacking. We aimed to map the regional colonic motility in response to ES of (a) the colonic tissue and (b) celiac branch of the abdominal vagus nerve (CBVN) in an anesthetized porcine model. METHODS: In male Yucatan pigs, direct ES (10 Hz, 2 ms, 15 mA) of proximal (pC), transverse (tC), or distal (dC) colon was done using planar flexible multi-electrode array panels and CBVN ES (2 Hz, 0.3-4 ms, 5 mA) using pulse train (PT), continuous (10 min), or square-wave (SW) modalities, with or without afferent nerve block (200 Hz, 0.1 ms, 2 mA). The regional luminal manometric changes were quantified as area under the curve of contractions (AUC) and luminal pressure maps generated. Contractions frequency power spectral analysis was performed. Contraction propagation was assessed using video animation of motility changes. KEY RESULTS: Direct colon ES caused visible local circular (pC, tC) or longitudinal (dC) muscle contractions and increased luminal pressure AUC in pC, tC, and dC (143.0 ± 40.7%, 135.8 ± 59.7%, and 142.0 ± 62%, respectively). The colon displayed prominent phasic pressure frequencies ranging from 1 to 12 cpm. Direct pC and tC ES increased the dominant contraction frequency band (1-6 cpm) power locally. Pulse train CBVN ES (2 Hz, 4 ms, 5 mA) triggered pancolonic contractions, reduced by concurrent afferent block. Colon contractions propagated both orally and aborally in short distances. CONCLUSION AND INFERENCES: In anesthetized pigs, the dominant contraction frequency band is 1-6 cpm. Direct colonic ES causes primarily local contractions. The CBVN ES-induced pancolonic contractions involve central neural network.

Biomechanical signaling and collagen fiber reorientation during distraction enterogenesis.

Distraction enterogenesis has been extensively studied as a potential treatment for short bowel syndrome, which is the most common subset of intestinal failure. Spring distraction uses an intraluminal axial mechanical force to stimulate the growth and elongation of the small intestine. The tissue close to the distracted intestinal segment may also experience signaling to grow. In this study we examined the effects of distraction enterogenesis at different post-operative days on the thickness of small intestinal layers in the intestine proximal and distal to the distracted segment, as well as how the submucosal collagen fibers were reoriented. It was observed that not only different layers of intestine wall in distracted segment showed thickening due to the applied mechanical force but also adjacent tissues in both distal and proximal directions were impacted significantly where they showed thickening as well. The orientation of collagen fibers in submucosa layer was also significantly impacted due to the mechanical force in both distracted and adjacent tissue. The effect of the applied mechanical force on the main distracted tissue and the radial growth of the adjacent tissue strongly suggest actions of paracrine signaling.

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.

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 ±â€¯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.

A Wireless Implantable System for Facilitating Gastrointestinal Motility.

Gastrointestinal (GI) electrical stimulation has been shown in several studies to be a potential treatment option for GI motility disorders. Despite the promising preliminary research progress, however, its clinical applicability and usability are still unknown and limited due to the lack of a miniaturized versatile implantable stimulator supporting the investigation of effective stimulation patterns for facilitating GI dysmotility. In this paper, we present a wireless implantable GI modulation system to fill this technology gap. The system consists of a wireless extraluminal gastrointestinal modulation device (EGMD) performing GI electrical stimulation, and a rendezvous device (RD) and a custom-made graphical user interface (GUI) outside the body to wirelessly power and configure the EGMD to provide the desired stimuli for modulating GI smooth muscle activities. The system prototype was validated in bench-top and in vivo tests. The GI modulation system demonstrated its potential for facilitating intestinal transit in the preliminary in vivo chronic study using porcine models.

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.

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.