The two devices described allow for greater control over application of a fibrin biopolymer and yet remain simple enough to be used by both medical personnel and by non-medical workers. One of the devices includes chambers where components necessary for formation of a fibrin biopolymer are stored and are pushed by plungers connected to an actuator upon the actuator receiving pressure from the user, with the components mixing in a chamber within the device and flowing out of a tube connected to the mixing chamber before formation of the fibrin biopolymer is completed. The other device dispenses formulations that include components necessary for formations of a fibrin biopolymer onto a skin of a patient using one or more propellants, with the formation of the fibrin biopolymer being initiated after the formulations are dispensed on the patient's skin and are intentionally mixed together.

The present disclosure provides variant immunomodulatory polypeptides, and fusion polypeptides comprising the variant immunomodulatory peptides. The present disclosure provides T-cell modulatory multimeric polypeptides, and compositions comprising same, where the T-cell modulatory multimeric polypeptides comprise a variant immunomodulatory polypeptide of the present disclosure. The present disclosure provides nucleic acids comprising nucleotide sequences encoding the T-cell modulatory multimeric polypeptides, and host cells comprising the nucleic acids. The present disclosure provides methods of modulating the activity of a T cell; the methods comprise contacting the T cell with a T-cell modulatory multimeric polypeptide of the present disclosure.

Disclosed are biodegradable nanocarriers that have a net positive surface charge and zeta potential between about +2 to about +20 mV. The positive surface charge of the nanocarriers is provided by peptides that are covalently attached to the surface of the nanocarriers. The nanocarriers may comprise a drug and may be administered for localized and sustained delivery of the drug.

Disclosed are biodegradable nanocarriers that have a net positive surface charge and zeta potential between about +2 to about +20 mV. The positive surface charge of the nanocarriers is provided by peptides that are covalently attached to the surface of the nanocarriers. The nanocarriers may comprise a drug and may be administered for localized and sustained delivery of the drug.

There is provided inter alia an isolated polynucleotide, wherein the polynucleotide encodes a polypeptide selected from the group consisting of: (a) a polypeptide having the amino acid sequence according to SEQ ID NO: 1, (b) a functional derivative of a polypeptide having the amino acid sequence according to SEQ ID NO: 1, wherein the functional derivative has an amino acid sequence which is at least 80% identical over its entire length to the amino acid sequence of SEQ ID NO: 1, and (c) a polypeptide having the amino acid sequence according to SEQ ID NO: 3.

There is provided inter alia an isolated polynucleotide, wherein the polynucleotide encodes a polypeptide selected from the group consisting of: (a) a polypeptide having the amino acid sequence according to SEQ ID NO: 1, (b) a functional derivative of a polypeptide having the amino acid sequence according to SEQ ID NO: 1, wherein the functional derivative has an amino acid sequence which is at least 80% identical over its entire length to the amino acid sequence of SEQ ID NO: 1, and (c) a polypeptide having the amino acid sequence according to SEQ ID NO: 3.

The present invention provides an in vitro method for identifying a compound that promotes endothelial cell adhesion, endothelial cell spreading, endothelial cell migration and/or endothelial cell proliferation for the manufacture of a diagnostic or therapeutic agent. The present invention further provides the identified compounds and pharmaceutical compositions, and assays and kits for identifying a compound or using a compound that promotes endothelial cell adhesion, endothelial cell spreading, endothelial cell migration and/or endothelial cell proliferation and is useful for bioprinting.

The present invention provides an in vitro method for identifying a compound that promotes endothelial cell adhesion, endothelial cell spreading, endothelial cell migration and/or endothelial cell proliferation for the manufacture of a diagnostic or therapeutic agent. The present invention further provides the identified compounds and pharmaceutical compositions, and assays and kits for identifying a compound or using a compound that promotes endothelial cell adhesion, endothelial cell spreading, endothelial cell migration and/or endothelial cell proliferation and is useful for bioprinting.

Described herein are compositions and techniques related to generation and therapeutic application of artificial synapses. Artificial synapses are engineered extracellular vesicles, including exosomes, which incorporate sticky binders on their surface to anchor signaling domains against biological targets, such as receptors. These engineered additives can be organized in genetic vector constructs, expressed in mammalian cells, wherein the sticky binders attach to extracellular vesicles such as exosomes, thereby presenting their joined signaling domains which are rapidly taken up by recipient cells. Artificial synapses adopt the hallmark biophysical and biochemical features of extracellular vesicles, allowing for rapid deployment and scale-up. Importantly, this strategy can allow for kinetically favorable signal generation and signal propagation. This includes, for example, increasing density of agonist presentation to support receptor clustering—an onerous barrier for traditional receptor targeting strategies.

This invention provides expressible polynucleotides, which can express a target protein or polypeptide. Synthetic mRNA constructs for producing a protein or polypeptide can contain one or more 5′ UTRs, where a 5′ UTR may be expressed by a gene of a plant. In some embodiments, a 5′ UTR may be expressed by a gene of a member of Arabidopsis genus. The synthetic mRNA constructs can be used as pharmaceutical agents for expressing a target protein or polypeptide in vivo.