Abstract: The subject matter disclosed herein is generally directed to modulation of genes and pathways that drive differentiation of LGR5+ stem cells. The methods and compositions can be used to treat diseases associated with aberrant epithelial barrier function. Using novel screening methods Applicants have identified compounds that increase Paneth cell differentiation. The compounds can be used to treat diseases associated with stem cell differentiation.

Abstract: Compositions formulated for release within the gastrointestinal tract and related methods are discussed. The composition may include a mucoadhesive agent and an active agent. The composition may be formulated for release of the active agent in a first direction while inhibiting release of the active agent in a second direction opposite the first direction.

Abstract: A system for delivering an injection of a fluid into a void within a subject is disclosed. A barrel extends from a first end to a second end and forms a lumen extending from the first end to the second end. A plug and a floating seal are arranged within the lumen. A hollow needle includes a distal end with an opening for fluid to flow from the lumen. The plug, the barrel and the floating seal include material and dimensions selected based on a threshold flowrate for a fluid arranged within the lumen to: overcome a force opposed to a force being applied to the fluid in the lumen to move the floating seal and the hollow needle into a tissue of the subject, and succumb to the opposing force to displace the fluid through the opening into the void.

Abstract: The subject matter disclosed herein is generally directed to modulation of genes and pathways that drive differentiation of LGR5+ stem cells. The methods and compositions can be used to treat diseases associated with aberrant epithelial barrier function.

Abstract: A system for delivering an injection of a fluid into a void within a subject is disclosed. A barrel extends from a first end to a second end and forms a lumen extending from the first end to the second end. A plug and a floating seal are arranged within the lumen. A hollow needle includes a distal end with an opening for fluid to flow from the lumen. The plug, the barrel and the floating seal include material and dimensions selected based on a threshold flowrate for a fluid arranged within the lumen to: overcome a force opposed to a force being applied to the fluid in the lumen to move the floating seal and the hollow needle into a tissue of the subject, and succumb to the opposing force to displace the fluid through the opening into the void.

Abstract: 3D cell cultures and devices for 3D cell culture, and methods of use thereof are provided. In some embodiments, the 3D cell culture comprise pancreatic ? cells and can be generated in multi-well plates, allowing for high throughput assays on the cell culture.

Abstract: A system and method is provided for detecting an analyte within a sample. The method includes providing a first electromagnetic radiation to the sample in a manner that resonantly excites mechanical vibrations in the analyte. The method also includes providing a second electromagnetic radiation to the sample so as to interact with vibrating analyte, wherein a third electromagnetic radiation is produced based on the interaction. The method further includes receiving the a third electromagnetic radiation and determining the presence of the analyte based on the received a third electromagnetic radiation.

Abstract: A system for delivering an injection of a fluid into a void within a subject is disclosed. A barrel extends from a first end to a second end and forms a lumen extending from the first end to the second end. A plug and a floating seal are arranged within the lumen. A hollow needle includes a distal end with an opening for fluid to flow from the lumen. The plug, the barrel and the floating seal include material and dimensions selected based on a threshold flowrate for a fluid arranged within the lumen to: overcome a force opposed to a force being applied to the fluid in the lumen to move the floating seal and the hollow needle into a tissue of the subject, and succumb to the opposing force to displace the fluid through the opening into the void.

Abstract: A self-assembled gel composition with enhanced adhesion to cartilage tissue is provided. A cationic agent co-self assembles with a generally regarded as safe (GRAS), low molecular weight (<2,500 Da) gelator, forming homogeneous self-supporting gel that can encapsulate one or more therapeutic agents for controlled release. The composition adheres to connective tissue, e.g., cartilage, to a greater extent and a greater length of time than a self-assembled gel from gelators alone. The composition is used to specifically target connective tissue and deliver one or more therapeutic, prophylactic, or diagnostic agents for controlled release to improve dosing efficacy.

Abstract: Disclosed here is a generally applicable framework that utilizes massively-parallel single-cell RNA-seq to compare cell types/states found in vivo to those of in vitro models. Furthermore, Applicants leverage identified discrepancies to improve model fidelity. Applicants uncover fundamental gene expression differences in lineage-defining genes between in vivo systems and in vitro systems. Using this information, molecular interventions are identified for rationally improving the physiological fidelity of the in vitro system. Applicants demonstrated functional (antimicrobial activity, niche support) improvements in Paneth cell physiology using the methods.

Abstract: Bone- and metal-targeted polymeric nanoparticles are provided. Exemplary nanoparticles have three main components: 1) a targeting element that can selectively bind to bone, minerals, or metal ions; 2) a layer of stealth to allow the polymer to evade immune response; and 3) a biodegradable polymeric material, forming an inner core which can carry therapeutics or other diagnostics. Preferred nanoparticles contain a blend of target-element polymer conjugate and polymer that optimizes the ligand density on the surface of the nanoparticle to provide improved targeting of the nanoparticle. The ratio of target-element polymer conjugate to polymer can also be optimized to improve the half-life of the nanoparticles in the blood of the subject. The nanoparticles also exhibit prolonged, sustained release of therapeutic agents loaded into the particles.

Abstract: Gels are formed based on generally recognized as safe (GRAS) low molecular weight amphiphilic molecules in a self-assembly process with limited or no heating. A selective range of ratios between an organic solvent and water, or an aqueous solution, in the medium, allows for the GRAS low molecular weight amphiphiles to form a homogeneous self-supporting gel encapsulating agents to be delivered under very mild conditions. Proteins including enzymes, antibodies, and serum albumin are loaded in the self-assembled gels to provide sustained and/or responsive delivery. The encapsulated proteins retain at least 70%, 80%, or 90% of their activity over days in various storage conditions.

Abstract: A self-assembled gel composition with enhanced adhesion to cartilage tissue is provided. A cationic agent co-self assembles with a generally regarded as safe (GRAS), low molecular weight (<2,500 Da) gelator, forming homogeneous self-supporting gel that can encapsulate one or more therapeutic agents for controlled release. The composition adheres to connective tissue, e.g., cartilage, to a greater extent and a greater length of time than a self-assembled gel from gelators alone. The composition is used to specifically target connective tissue and deliver one or more therapeutic, prophylactic, or diagnostic agents for controlled release to improve dosing efficacy.

Abstract: An adhesive article includes a biocompatible and at least partially biodegradable substrate having a surface; and a plurality of protrusions extending from the surface. The protrusions include a biocompatible and at least partially biodegradable material, and have an average height of less than approximately 1,000 micrometers.

Abstract: Bone- and metal-targeted polymeric nanoparticles are provided. Exemplary nanoparticles have three main components: 1) a targeting element that can selectively bind to bone, minerals, or metal ions; 2) a layer of stealth to allow the polymer to evade immune response; and 3) a biodegradable polymeric material, forming an inner core which can carry therapeutics or other diagnostics. Preferred nanoparticles contain a blend of target-element polymer conjugate and polymer that optimizes the ligand density on the surface of the nanoparticle to provide improved targeting of the nanoparticle. The ratio of target-element polymer conjugate to polymer can also be optimized to improve the half-life of the nanoparticles in the blood of the subject. The nanoparticles also exhibit prolonged, sustained release of therapeutic agents loaded into the particles.

Abstract: An adhesive article includes a biocompatible and at least partially biodegradable substrate having a surface; and a plurality of protrusions extending from the surface. The protrusions include a biocompatible and at least partially biodegradable material, and have an average height of less than approximately 1,000 micrometers.

Abstract: Culturing embryonic stem cells without the use of embryoid bodies leads to a increase in the frequency of predetermined cell types.