An ingestible self-propelling device for intestinal reanimation.

Postoperative ileus (POI) is the leading cause of prolonged hospital stay after abdominal surgery and is characterized by a functional paralysis of the digestive tract, leading to symptoms such as constipation, vomiting, and functional obstruction. Current treatments are mainly supportive and inefficacious and yield acute side effects. Although electrical stimulation studies have demonstrated encouraging pacing and entraining of the intestinal slow waves, no devices exist today to enable targeted intestinal reanimation. Here, we developed an ingestible self-propelling device for intestinal reanimation (INSPIRE) capable of restoring peristalsis through luminal electrical stimulation. Optimizing mechanical, material, and electrical design parameters, we validated optimal deployment, intestinal electrical luminal contact, self-propelling capability, safety, and degradation of the device in ex vivo and in vivo swine models. We compared the INSPIRE's effect on motility in models of normal and depressed motility and chemically induced ileus. Intestinal contraction improved by 44% in anesthetized animals and up to 140% in chemically induced ileus cases. In addition, passage time decreased from, on average, 8.6 days in controls to 2.5 days with the INSPIRE device, demonstrating significant improvement in motility. Luminal electrical stimulation of the intestine via the INSPIRE efficaciously restored peristaltic activity. This noninvasive option offers a promising solution for the treatment of ileus and other motility disorders.

A vibrating ingestible bioelectronic stimulator modulates gastric stretch receptors for illusory satiety.

Effective therapies for obesity require invasive surgical and endoscopic interventions or high patient adherence, making it challenging for patients with obesity to effectively manage their disease. Gastric mechanoreceptors sense distension of the stomach and perform volume-dependent vagal signaling to initiate the gastric phase and influence satiety. In this study, we developed a new luminal stimulation modality to specifically activate these gastric stretch receptors to elicit a vagal afferent response commensurate with mechanical distension. We designed the Vibrating Ingestible BioElectronic Stimulator (VIBES) pill, an ingestible device that performs luminal vibratory stimulation to activate mechanoreceptors and stroke mucosal receptors, which induces serotonin release and yields a hormonal metabolic response commensurate with a fed state. We evaluated VIBES across 108 meals in swine which consistently led to diminished food intake (~40%, P < 0.0001) and minimized the weight gain rate (P < 0.05) as compared to untreated controls. Application of mechanoreceptor biology could transform our capacity to help patients suffering from nutritional disorders.

A Vibrating Ingestible BioElectronic Stimulator Modulates Gastric Stretch Receptors for Illusory Satiety.

Effective therapies for obesity either require invasive surgical or endoscopic interventions or high patient adherence, making it challenging for the nearly 42% of American adults who suffer from obesity to effectively manage their disease. Gastric mechanoreceptors sense distension of the stomach and perform volume-dependent vagal signaling to initiate the gastric phase and influence satiety. In this study, we developed a new luminal stimulation modality to specifically activate these gastric stretch receptors to elicit a vagal afferent response commensurate with mechanical distension. Here we developed the Vibrating Ingestible BioElectronic Stimulator (VIBES) pill - an ingestible device that performs luminal vibratory stimulation to activate mechanoreceptors and stroke mucosal receptors, which induces serotonin release as well as yields a hormonal metabolic response commensurate with a fed state. We evaluated VIBES across 108 meals in swine which consistently led to diminished food intake (~40%, p< 0.0001) and minimized the weight gain rate (p< 0.03) as compared to untreated controls. Application of mechanoreceptor biology could transform our capacity to help patients suffering from nutritional disorders.

Adaptive conductive electrotherapeutic scaffolds for enhanced peripheral nerve regeneration and stimulation.

BACKGROUND: While peripheral nerve stimulation (PNS) has shown promise in applications ranging from peripheral nerve regeneration to therapeutic organ stimulation, clinical implementation has been impeded by various technological limitations, including surgical placement, lead migration, and atraumatic removal. METHODS: We describe the design and validation of a platform technology for nerve regeneration and interfacing: adaptive, conductive, and electrotherapeutic scaffolds (ACESs). ACESs are comprised of an alginate/poly-acrylamide interpenetrating network hydrogel optimized for both open surgical and minimally invasive percutaneous approaches. FINDINGS: In a rodent model of sciatic nerve repair, ACESs significantly improved motor and sensory recovery (p < 0.05), increased muscle mass (p < 0.05), and increased axonogenesis (p < 0.05). Triggered dissolution of ACESs enabled atraumatic, percutaneous removal of leads at forces significantly lower than controls (p < 0.05). In a porcine model, ultrasound-guided percutaneous placement of leads with an injectable ACES near the femoral and cervical vagus nerves facilitated stimulus conduction at significantly greater lengths than saline controls (p < 0.05). CONCLUSION: Overall, ACESs facilitated lead placement, stabilization, stimulation, and atraumatic removal, enabling therapeutic PNS as demonstrated in small- and large-animal models. FUNDING: This work was supported by K. Lisa Yang Center for Bionics at MIT.

RoboCap: Robotic mucus-clearing capsule for enhanced drug delivery in the gastrointestinal tract.

Oral drug delivery of proteins is limited by the degradative environment of the gastrointestinal tract and poor absorption, requiring parenteral administration of these drugs. Luminal mucus represents the initial steric and dynamic barrier to absorption. To overcome this barrier, we report the development of the RoboCap, an orally ingestible, robotic drug delivery capsule that locally clears the mucus layer, enhances luminal mixing, and topically deposits the drug payload in the small intestine to enhance drug absorption. RoboCap's mucus-clearing and churning movements are facilitated by an internal motor and by surface features that interact with small intestinal plicae circulares, villi, and mucus. Vancomycin (1.4 kilodaltons of glycopeptide) and insulin (5.8 kilodaltons of peptide) delivery mediated by RoboCap resulted in enhanced bioavailability 20- to 40-fold greater in ex vivo and in vivo swine models when compared with standard oral delivery (P < 0.05). Further, insulin delivery via the RoboCap resulted in therapeutic hypoglycemia, supporting its potential to facilitate oral delivery of drugs that are normally precluded by absorption limitations.