Abstract: Disclosed herein is a system that engages skin-resident APCs by directly delivering a vaccine composition, and a system that turns skin cells into a vaccine dispatch center to amplify immunity via the production of engineered extracellular vesicles (EVs) functionalized with targeting ligands and loaded with the vaccine composition that can be targeted to extracutaneous APCs. In particular, disclosed herein is a vaccine composition that involves a first polynucleotide encoding or comprising a viral, bacterial, or tumor antigen, and a second polynucleotide encoding a fusion protein comprising an APC-targeting ligand and an exosomal or lysosomal transmembrane protein. Also disclosed is a method of vaccinating a subject that involves transfecting skin cells of the subject with the disclosed vaccine composition. Also disclosed herein is a method of vaccinating a subject that involves administering to the subject the disclosed EV vaccine.

Abstract: Disclosed herein are designer extracellular vesicles (EVs) functionalized with glutamate receptors (e.g., mGluR4 and mGluR8), which can selectively target injured regions of the CNS experiencing excitotoxicity. mGluR4 and mGluR8-decorated EVs preferentially anchor into injured areas of the CNS with a marked increase in extracellular glutamate associated with profuse neuroand excitotoxicity. Therefore, glutamate receptor decoration can lead to enhanced homing in glutamate-rich areas of the CNS.

Abstract: Described herein are electrospun core-shell fibers that include (i) a central core that is electrically conductive having an exterior surface, wherein the core comprises a first polymer and an electroconductive material; (ii) a shell adjacent to the exterior surface of the core, the shell comprising a second polymer; and (iii) one or more bioactive agents in the shell. In one aspect, the fibers are electrospun fibers. Additionally, described herein are methods for making and using the core-shell fibers.

Abstract: As disclosed herein, the skin can dispatch signals to the brain in the form of exosomes, referred to herein as a “skin-brain axis.” Therefore, disclosed herein is a method for diagnosing a brain disease, disorder, or injury in a subject that involves isolating exosomes from the subject and assaying the exosomes for the presence of one or more biomarkers of the disease, disorder, or injury. Also disclosed are methods of treating a subject with a brain disease, disorder, or injury that involves engineering the skin of the subject to produce therapeutic exosomes. Also disclosed are methods of collecting skin-produced exosomes and loading them with therapeutic cargo that can treat one or more diseases, disorders, or injuries of the brain. Also disclosed herein is a method to reduce exosomal release from the skin to reducing trafficking to the brain.

Abstract: Provided herein are devices and methods for topically and controllably delivering cargo or collecting samples into or from biological tissues, particularly the skin. These devices permit delivery of cargo and collection of samples from cell layers deep within a tissue. These devices include microstructure arrays comprising nanochannels. Also disclosed is a device comprising a one or more microstructure arrays encased in a frame.

Abstract: Disclosed herein are compositions and methods for reprogramming diseased musculoskeletal cells both in vitro and in vivo. In some embodiments, the disclosed method involves non-virally delivering intracellularly into the diseased musculoskeletal cells a polynucleotide comprising one or more nucleic acid sequences encoding one or more of the disclosed transcription factors.

Abstract: Provided herein are devices and methods for topically and controllably delivering cargo across or into biological tissues, particularly the skin. These devices permit delivery of cargo to deeper cell layers of a tissue. These devices include microstructure arrays comprising nanochannels. Also disclosed is a device comprising a one or more microstructure arrays encased in a frame.

Abstract: Disclosed herein is a method of “reprogramming” highly motile cells found in tumors, such as these highly motile GSC and/or MDSC clones, into “auto-destructive” cell “missiles” (referred to herein as therapeutic stealth cells) that can seek and destroy new foci of recurrence within the body, such as the brain. Cells with enhanced motility can be sorted out from heterogeneous populations and then be rendered “auto-destructive” by deterministic delivery of an anti-cancer agent, such as an oncolytic virus plasmid cocktail.

Abstract: Disclosed herein are compositions and methods that involve using compositions for directly reprogramming skin cells into insulin-producing cells both in vitro and in vivo. These compositions and methods are useful for a variety of purposes, including the treatment of insulin-dependent and insulin-resistant diabetes. Therefore, also disclosed is a method for treating diabetes in a subject that involves reprogramming an effective amount of skin cells in the subject into an insulin producing cell using the method disclosed herein.

Abstract: Disclosed are lung-targeted extracellular vesicles (EVs) loaded with an anti-inflammatory cargo, as well as compositions, systems, and methods for making same. The disclosed EVs can contain a lung targeted ligand, such as a fusion protein containing a lung targeting moiety. Also disclosed is a composition comprising an EV containing the disclosed fusion protein. In some embodiments, the EV is loaded with an anti-inflammatory cargo. Also disclosed is an EV-producing cell engineered to produce the disclosed EVs. Also disclosed is a method for making the disclosed EVs that involves culturing the disclosed EV-producing cells under conditions suitable to produce EVs.

Abstract: Disclosed herein are MDSC-targeted extracellular vesicles (EVs) loaded with therapeutic cargo, as well as compositions, systems, and methods for making same. Also disclosed herein is an MDSC-targeting ligand, such as a fusion protein containing an MDSC-targeting moiety. Also disclosed are EVs containing the disclosed fusion protein. In some embodiments, the EV is also loaded with a therapeutic cargo. Also disclosed is an EV-producing cell engineered to produce the disclosed EVs. Also disclosed is a method for making the disclosed EVs that involves culturing the disclosed EV-producing cells under conditions suitable to produce EVs.

Abstract: Provided herein are devices and methods for topically and controllably delivering cargo across or into biological tissues, particularly the skin. These devices permit delivery of cargo to deeper cell layers of a tissue. These devices include microstructure arrays comprising nanochannels. Also disclosed is a device comprising a one or more microstructure arrays encased in a frame.