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: Among other things, the present disclosure provides compositions and methods for an elastomeric cross-linked polyester material. Such an elastomeric cross-linked polyester material, in some embodiments, comprises a plurality of polymeric units of the general formula (-A-B-)p, wherein p is an integer greater than 1; and a plurality of urethane cross-links each of which covalently links two polymeric units to one another, which two linked polymeric unit each had at least one free hydroxyl or amino group prior to formation of the crosslink.

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.

Abstract: Provided herein are new cyclodextrin-based compounds, and pharmaceutically acceptable salts, stereoisomers, and isotopically labeled derivatives thereof, which are capable of binding sugars (e.g., glucose). The compounds provided herein may be conjugated to agents or tags (e.g., therapeutic agents such as insulin) to form conjugates. In another aspect, also provided herein are pharmaceutical compositions comprising the compounds and conjugates described herein. The compounds and conjugates described herein are capable of binding glucose; therefore, provided herein are methods of sensing or detecting glucose comprising contacting glucose with the compound or conjugate. In another aspect, also provided herein are methods of treating a disease (e.g., a metabolic disorder, such as diabetes) in a subject comprising administering to the subject a compound, conjugate, or composition provided herein.

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: Method and compositions for inducing the self-renewal of stem/progenitor supporting cells comprised by a cochlear cell population, including inducing the stem/progenitor cells to proliferate while maintaining, in the daughter cells, the capacity to differentiate into hair cells.

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 5 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 certain embodiments, the self-righting article a tissuel0 interfacing components. In some embodiments, each tissue-interfacing component may comprise an electrically-conductive portion configured for electrical communication with tissue and an insulative portion configured to not be in electrical communication with tissue.

Abstract: Triggerable hydrogel compositions and related methods are generally disclosed. In some embodiments, the compositions and related methods may be used for medical-related or other applications. For example, the compositions and methods described herein may be useful, for example, in biomedical applications such as articles for (e.g., gastric) retention. In some embodiments, methods for deploying and/or removing an article comprising the composition, such as an article for gastric retention, are provided. The article and/or composition may be removed internally from a subject by, for example, introducing at least one reagent (e.g., one reagent, two reagents) such that at least a portion of the composition disassociates. In certain embodiments, the composition comprises a polymer network comprising two or more interpenetrating polymers. In some cases, a first polymer comprises a first cross-link moiety configured to dissociate upon interaction with a reagent.

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: The present application provides compositions and methods for determining a disease or condition in a subject. The method comprises contacting a body fluid with a molecule comprising a reporter thereof and the reported is cleaved by an agent in the body fluid. Diseases and conditions that can be determined by the method are also described.

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: Covalently modified alginate polymers, possessing enhanced biocompatibility and tailored physiochemical properties, as well as methods of making and use thereof, are disclosed herein. The covalently modified alginates are useful as a matrix for the encapsulation and transplantation of cells. Also disclosed are high throughput methods for the characterizing the biocompatibility and physiochemical properties of modified alginate polymers.

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: Neurological implants whose surfaces have been chemically and covalently modified to impart beneficial properties to the neurological implants are described. The neurological implants possess improved biocompatibility compared to a corresponding neurological implant that lacks the chemical modification. Following implantation in a subject, the surface-modified neurological implants induce a lower-foreign body response, compared to a corresponding unmodified product.

Abstract: A platform technology has been designed to provide a means for controlled delivery of single or multiple doses of therapeutic, prophylactic, diagnostic or identifying agents to livestock. The delivery system is based on a livestock ear tag that releases therapeutic and/or prophylactic agent when applied to the ear or other desired anatomical target of the animal. The agent to be delivered is encapsulated in or on microneedles and or microparticles and or nanoparticles or combination thereof on a surface thereon of the male or female part of the tag, which is pressed into the skin so that the microneedles penetrate into the epidermis and dermis layers of the skin. The agent is then released into the animal from the microneedles and or microparticles and or nanoparticles or combination thereof at the site of contact into the epidermis and dermis layers of the skin.

Abstract: The present disclosure provides, in some embodiments, in vitro brain (miBRAIN) having functional and structural properties of in vivo brain as well as methods of identifying compounds capable of influencing brain function.

Abstract: The present application provides compositions and methods for determining a disease or condition in a subject. The method comprises contacting a body fluid with a molecule comprising a reporter thereof and the reported is cleaved by an agent in the body fluid. Diseases and conditions that can be determined by the method are also described.

Abstract: The present application provides compositions and methods for determining a disease or condition in a subject. The method comprises contacting a body fluid with a molecule comprising a reporter thereof and the reported is cleaved by an agent in the body fluid. Diseases and conditions that can be determined by the method are also described.

Abstract: Components with relatively high loading of active pharmaceutical ingredients are generally provided. In some embodiments, the component (e.g., a tissue interfacing component) comprises a solid therapeutic agent and a supporting material 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: Apparatus, kits, and methods for administering a substance are presented. A device for administering a substance includes an elongated body having a proximal end and a distal end, the elongated body defining an internal chamber extending between the proximal end and the distal end to direct the substance to the distal end, the distal end to connect with a tip, the tip to be at least partially inserted into an orifice of a body lumen of a subject, the tip having a shape configured to reduce leakage of the substance from the orifice upon the at least partial insertion. The tip includes an opening to pass the substance from the internal chamber into the body lumen; and a transducer to emit an ultrasound wave from the tip into the body lumen, thereby administering the substance to tissue in the body lumen.