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.

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.

A method for manufacturing a fibrinogen preparation from a fibrinogen containing source derived from blood plasma includes providing a liquid phase containing plasmatic fibrinogen; contacting the liquid phase with a cation exchange chromatography material under conditions resulting in binding of fibrinogen, wherein the liquid phase has a pH in the range of pH 5.6 to pH 7.0 which is near or above the pl of fibrinogen; optionally washing unbound compounds from the cation exchange chromatography material; and eluting the fibrinogen from the cation exchange material. The method is also suitable for reduction of von-Willebrand-factor.

A method for manufacturing a fibrinogen preparation from a fibrinogen containing source derived from blood plasma includes providing a liquid phase containing plasmatic fibrinogen; contacting the liquid phase with a cation exchange chromatography material under conditions resulting in binding of fibrinogen, wherein the liquid phase has a pH in the range of pH 5.6 to pH 7.0 which is near or above the pl of fibrinogen; optionally washing unbound compounds from the cation exchange chromatography material; and eluting the fibrinogen from the cation exchange material. The method is also suitable for reduction of von-Willebrand-factor.

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.

Described herein are novel methods for fractionating and isolating platelets, platelet- and extracellular vesicle-derived growth factors, exosomes, globulins, fibrinogen and albumin, and methods of using the isolated platelets, platelet and extracellular vesicle-derived growth factors, exosomes, globulins, fibrinogen and albumin for regenerating tissue in a subject, treating fibrinogenemia or a clotting deficiency in a subject, treating ischemia and hypoxia, treating dry-eye syndrome, an orthopedic disorder, or a dental disorder in a subject. Also described herein are growth media for culturing mammalian (e g , human) cells.

Efficient methods for capture and removal of fibrinogen from blood plasma fractions, especially cryoprecipitate, and Fraction II+III providing high yields of blood coagulation Factor VIII are disclosed. According to this disclosure, there is provided a method of separating plasma cryoprecipitate or Fraction II+III comprising a blood coagulation factor and fibrinogen into a first fraction comprising the blood coagulation factor and a second fraction containing the fibrinogen, the method comprising: (a) contacting he plasma cryoprecipitate with solid SiO.sub.2 or Al(OH).sub.3, thereby adsorbing the fibrinogen onto the solid SiO.sub.2 or Al(OH).sub.3; and (b) separating the fibrinogen adsorbed onto the solid SiO.sub.2 or Al(OH).sub.3 from the blood factor, thereby forming the first fraction and the second fraction.

Efficient methods for capture and removal of fibrinogen from blood plasma fractions, especially cryoprecipitate, and Fraction II+III providing high yields of blood coagulation Factor VIII are disclosed. According to this disclosure, there is provided a method of separating plasma cryoprecipitate or Fraction II+III comprising a blood coagulation factor and fibrinogen into a first fraction comprising the blood coagulation factor and a second fraction containing the fibrinogen, the method comprising: (a) contacting he plasma cryoprecipitate with solid SiO.sub.2 or Al(OH).sub.3, thereby adsorbing the fibrinogen onto the solid SiO.sub.2 or Al(OH).sub.3; and (b) separating the fibrinogen adsorbed onto the solid SiO.sub.2 or Al(OH).sub.3 from the blood factor, thereby forming the first fraction and the second fraction.

Efficient methods for capture and removal of fibrinogen from blood plasma fractions, especially cryoprecipitate, and Fraction II+III providing high yields of blood coagulation Factor VIII are disclosed. According to this disclosure, there is provided a method of separating plasma cryoprecipitate or Fraction II+III comprising a blood coagulation factor and fibrinogen into a first fraction comprising the blood coagulation factor and a second fraction containing the fibrinogen, the method comprising: (a) contacting he plasma cryoprecipitate with solid SiO.sub.2 or Al(OH).sub.3, thereby adsorbing the fibrinogen onto the solid SiO.sub.2 or Al(OH).sub.3; and (b) separating the fibrinogen adsorbed onto the solid SiO.sub.2 or Al(OH).sub.3 from the blood factor, thereby forming the first fraction and the second fraction.

A method for producing a fibrin sheet containing at least one selected from the group consisting of cells and drugs in a fibrin gel, the method comprising: a step 1 of applying a fibrinogen solution containing at least one selected from the group consisting of cells and drugs and fibrinogen dropwise onto a surface of a substrate made of a gelatin hydrogel; a step 2 of adding thrombin to the fibrinogen solution on the surface of the substrate; a step 3 of placing a support film on and in contact with a top surface of the fibrinogen solution to which the thrombin has been added; a step 4 of forming a fibrin sheet containing the at least one selected from the group consisting of cells and drugs in a fibrin gel between the substrate and the support film by a reaction between the fibrinogen and the thrombin; and a step 5 of melting the substrate at a temperature not lower than a melting temperature of the gelatin hydrogel to separate, from the substrate, the fibrin sheet supported by the support film.