Abstract: An ex vivo tissue composition comprising an isolated tissue explant and tissue graft is provided. Methods of making and using the tissue composition are also provided.

Abstract: The present disclosure provides compositions, methods, and kits that enable the in situ growth of polymers on or within a subject. In some aspects, the tissue-active monomers, including monomers comprising macromolecules, provide abroad set of material choices for synthetic tissue barriers. In additional aspects, the compositions, methods, and kits are useful for treating or preventing a disease or disorder.

Abstract: Articles and systems configured for treating GI motility disorders are generally provided. In some embodiments, an article comprising one or more electrodes (with both sensing and stimulating capabilities) may be configured to stimulate one or more tissues in the GI tract, electrically and/or chemically, to modulate peristalsis and/or allow neuromodulation. In some embodiments, a system comprises a controller that allows for close-loop operation of the article, e.g., such that the article may stimulate (e.g., via a feedback loop) the one or more organs in the GI tract upon receiving sensed parameters in the GI tract. In some embodiments, an implantation tool comprising a sensor may allow for submucosal or intramuscular implantation of an article. The implantation tool and the article may be useful for, for example, as a general platform for delivery of treating GI motility disorders and/or neuromodulation of the GI tract.

Abstract: Self-righting articles, such as self-righting capsules for administration to a subject, are generally provided. In some embodiments, the self-righting article may be configured such that the article may orient itself relative to a surface. The self-righting articles described herein may comprise one or more tissue engaging surfaces configured to engage with a surface. In some embodiments, the self-righting article may have a particular shape and/or distribution of density (or mass) which, for example, enables the self-righting behavior of the article. In some embodiments, the self-righting article may comprise a tissue interfacing component and/or a pharmaceutical agent (e.g., for delivery of the active pharmaceutical agent to a location internal of the subject). In some cases, upon contact of the tissue with the tissue engaging surface of the article, the self-righting article may be configured to release one or more tissue interfacing components.

Abstract: Self-righting articles, such as self-righting capsules for administration to a subject, are generally provided. In some embodiments, the self-righting article may be configured such that the article may orient itself relative to a surface (e.g., a surface of a tissue of a subject). The self-righting articles described herein may comprise one or more tissue engaging surfaces configured to engage (e.g., interface with, inject into, anchor) with a surface (e.g., a surface of a tissue of a subject). In some embodiments, the self-righting article may have a particular shape and/or distribution of density (or mass) which, for example, enables the self-righting behavior of the article. In some embodiments, the self-righting article may comprise a tissue interfacing component and/or a pharmaceutical agent (e.g., for delivery of the active pharmaceutical agent to a location internal of the subject).

Abstract: Drug delivery articles, resident articles, and retrieval systems e.g., for gram-level dosing, are generally provided. In some embodiments, the articles are configured for transesophageal administration, transesophageal retrieval, and/or gastric retention to/in a subject. In certain embodiments, the article includes dimensions configured for transesophageal administration with a gastric resident system. In some cases, the article may be configured to control drug release e.g., with zero-order drug kinetics with no potential for burst release for weeks to months. In some embodiments, the articles described herein comprise biocompatible materials and/or are safe for gastric retention. In certain embodiments, the article includes dimensions configured for transesophageal retrieval. In some cases, the articles described herein may comprise relatively large doses of drug (e.g., greater than or equal to 1 gram).

Abstract: Residence structures, systems, and related methods are generally provided. Certain embodiments comprise administering (e.g., orally) a residence structure to a subject (e.g., a patient) such that the residence structure is retained at a location internal to the subject for a particular amount of time (e.g., at least about 24 hours) before being released. The residence structure may be, in some cases, a gastric residence structure. In some embodiments, the structures and systems described herein comprise one or more materials configured for high levels of active substances (e.g., a therapeutic agent) loading, high active substance and/or structure stability in acidic environments, mechanical flexibility and strength in an internal orifice (e.g., gastric cavity), easy passage through the GI tract until delivery to at a desired internal orifice (e.g., gastric cavity), and/or rapid dissolution/degradation in a physiological environment (e.g., intestinal environment) and/or in response to a chemical stimulant (e.

Abstract: A device may be configured with a housing having a reservoir and an outlet separated by a heat rupturable membrane. The membrane may serve to separate a material held within the reservoir from the outlet until the membrane is ruptured. The membrane may include a heater configured to selectively rupture the membrane when actuated. The heater may be physically removed and/or thermally insulated from at least one of an environment surrounding the device and the reservoir.

Abstract: Improvements in ingestible electronics with the capacity to sense physiologic and pathophysiologic states have transformed the standard of care for patients. Yet despite advances in device development, significant risks associated with solid, non-flexible gastrointestinal transiting systems remain. Here, we disclose an ingestible, flexible piezoelectric device that senses mechanical deformation within the gastric cavity. We demonstrate the capabilities of the sensor in both in vitro and ex vivo simulated gastric models, quantified its key behaviors in the GI tract by using computational modeling, and validated its functionality in awake and ambulating swine. Our piezoelectric devices can safely sense mechanical variations and harvest mechanical energy inside the gastrointestinal tract for diagnosing and treating motility disorders and for monitoring ingestion in bariatric applications.

Abstract: Delivery systems and their methods of use for delivering one or more therapeutic compounds to a user are described. A delivery system may include an implantable pump and an external actuator. The implantable pump may include an actuatable portion that may be actuated to dispense a volume of fluid. The external actuator may include a pusher configured to deform skin to engage an actuatable portion of the pump. The external actuator may also include a positioning magnet configured to magnetically attract a portion of the implantable pump such that the external actuator and the pump may be aligned prior to applying force to the portion of the skin between the external actuator and the actuatable portion of the pump.

Abstract: Self-righting articles, such as self-righting capsules for administration to a subject, are generally provided. In some embodiments, the self-righting article may be configured such that the article may orient itself relative to a surface (e.g., a surface of a tissue of a subject). The self-righting articles described herein may comprise one or more tissue engaging surfaces configured to engage (e.g., interface with, inject into, anchor) with a surface (e.g., a surface of a tissue of a subject). In some embodiments, the self-righting article may have a particular shape and/or distribution of density (or mass) which, for example, enables the self-righting behavior of the article. In some embodiments, the self-righting article may comprise a tissue interfacing component and/or a pharmaceutical agent (e.g., for delivery of the active pharmaceutical agent to a location internal of the subject).

Abstract: Methods of manufacturing tissue interfacing components, such as solid needles comprising one or more therapeutic agents, are disclosed. In some embodiments, a method for manufacturing a tissue interfacing component comprises compressing a granular therapeutic agent within a mold cavity of a mold to form a solid tissue interfacing component. The mold cavity may define an elongated shape extending along a longitudinal axis from an opening of the mold cavity to a distal end of the mold cavity, and the granular therapeutic agent may be compressed by moving a mold punch along the longitudinal axis towards the distal end. After compressing the granular therapeutic agent to form the solid tissue interfacing component, the tissue interfacing component may be removed from the mold and subsequently inserted into tissue to deliver the therapeutic agent to a subject.

Abstract: Self-righting articles, such as self-righting capsules for administration to a subject, are generally provided. In some embodiments, the self-righting article may be configured such that the article may orient itself relative to a surface (e.g., a surface of a tissue of a subject). The self-righting articles described herein may comprise one or more tissue engaging surfaces configured to engage (e.g., interface with, inject into, anchor) with a surface (e.g., a surface of a tissue of a subject). In some embodiments, the self-righting article may have a particular shape and/or distribution of density (or mass) which, for example, enables the self-righting behavior of the article. In some embodiments, the self-righting article may comprise a tissue interfacing component and/or a pharmaceutical agent (e.g., for delivery of the active pharmaceutical agent to a location internal of the subject).

Abstract: Transient molecules in the gastrointestinal (GI) tract, such as nitric oxide and hydrogen sulfide, are important signals and mediators of inflammatory bowel disease (IBD). Because these molecules may be short-lived in the body, they are difficult to detect. To track these reactive molecules in the GI tract, a miniaturized device has been developed that integrates genetically engineered probiotic biosensors with a custom-designed photodetector and readout chip. Leveraging the molecular specificity of living sensors, bacteria were genetically encoded to respond to IBD-associated molecules by luminescing. Low-power electronic readout circuits (e.g., using nanowatt power) integrated into the device convert the light from just 1 ?L of bacterial culture into a wireless signal. Biosensor monitoring was demonstrated in the GI tract of small and large animal models and integration of all components into a sub-1.4 cm3 ingestible form factor capable of supporting wireless communication.

Abstract: An all-in-one insulin pen includes a handheld housing that houses a glucose testing module, an insulin delivery module, a wireless communication module, and a microcontroller. The glucose testing module tests a one-time glucose concentration of a patient. The insulin delivery module automatically administers an insulin bolus to the patient based at least in part on the one-time glucose concentration.

Abstract: The present disclosure provides branched poly(?-amino esters) (PBAEs) of Formula (I) made by reacting primary amines with diacrylates. Further provided herein are compositions comprising the polymers of Formula (I), and methods of using the compositions and polymers as described herein for the treatment of disease.

Abstract: Components with relatively high loading of active pharmaceutical ingredients (e.g., drugs), are generally provided. In some embodiments, the component (e.g., a tissue interfacing component) comprises a solid therapeutic agent (e.g., a solid API) and a supporting material (e.g., a binder such as a polymer) such that the solid therapeutic agent is present in the component in an amount of greater than or equal to 10 wt % versus the total weight of the tissue interfacing component. Such tissue-interfacing components may be useful for delivery of API doses e.g., to a subject. Advantageously, in some embodiments, the reduction of volume required to deliver the required API dose as compared to a liquid formulation permits the creation of solid needle delivery systems for a wide variety of drugs in a variety of places/tissues (e.g., tongue, GI mucosal tissue, skin) and/or reduces and/or eliminates the application of an external force in order to inject a drug solution through the small opening in the needle.

Abstract: Self-actuating articles including, for example, self-actuating needles and/or self-actuating biopsy punches, are generally provided. Advantageously, the self-actuating articles described herein may be useful as a general platform for delivery of a wide variety of pharmaceutical drugs that are typically delivered via injection directly into tissue due to degradation in the GI tract. The self-actuating articles described herein may also be used to deliver sensors and/or take biopsies without the need for an endoscopy. In some embodiments, the article comprises a spring (e.g., a coil spring, a beam, a material having particular mechanical recovery characteristics).

Abstract: Certain embodiments comprise administering a residence structure to a subject (e.g., a patient) such that the residence structure is retained at a location internal to the subject for a particular amount of time (e.g., at least about 24 hours) before being released. In certain embodiments, the structure has a modular design, combining a material configured for controlled release of therapeutic, diagnostic, and/or enhancement agents with a structural material necessary for gastric residence but configured for controlled and/or tunable degradation/dissolution to determine the time at which retention shape integrity is lost and the structure passes out of the gastric cavity. For example, in certain embodiments, the residence structure comprises a first elastic component, a second component configured to release an active substance, and, optionally, a linker. In some such embodiments, the linker may be configured to degrade.

Abstract: Articles and methods for delivering a therapeutic agent to a subject are described. These articles and methods may be useful, in some cases, for the delivery of therapeutic agents to the colon of a subject. In some embodiments, an article is configured to release a secretion inducing agent e.g., to stimulate the release of intestinal fluids. The article, in some embodiments, comprises a therapeutic agent such that the stimulated release of intestinal fluid increases the amount of therapeutic agent available for absorption by the colon. For example, in some embodiments, the articles and methods described herein advantageously promote increased absorption of therapeutic agents in subjects as compared to traditionally administered therapeutic agents without additional components such as a secretion inducing agent. In some embodiments, articles and methods described herein may increase the motility of the colon of a subject.