The invention relates to compositions and methods for the preparation, manufacture and therapeutic use of polynucleotides, primary transcripts and mmRNA molecules.

A method of sealing a durotomy from which cerebrospinal fluid is leaking. A durotomy sealant dressing is prepared by applying an active agent to a dextran base. The durotomy sealant dressing is applied to a durotomy. At least a portion of the durotomy sealant dressing dissolves. The durotomy is sealed with the dissolved durotomy sealant dressing to substantially prevent cerebrospinal fluid from flowing through the durotomy.

Provided herein is a plasma-supplemented fibrinogen and/or fibrin formulation, method for the preparation and use thereof.

A hydrogel precursor formulation which is in the form of an unreacted powder. The formulation comprises an activating enzyme, preferably thrombin, a cross-linking enzyme, preferably a transglutaminase, and more preferably factor XIII transglutaminase. The cross-linking enzyme is activatable by the activating enzyme in water with or without a buffer, and at least one structural compound A. The structural compound is crosslinkable by a selective reaction mediated by the crosslinking enzyme to form a hydrogel, wherein the cross-linking enzyme is activated.

Compositions and methods for therapeutic delivery are disclosed. More particularly, the present disclosure relates to nanoparticle compositions that sequester the activity of a target molecule while leaving other domains accessible to bind targeted tissues of interest. Methods for thrombus dissolution include administering a nanoparticle reversibly coupled to a target molecule that can dissolve a blood clot. Compositions and methods for inducing blood clotting are also disclosed. Methods for inducing blood clotting include administering a nanoparticle reversibly coupled to a target molecule that can induce the formation of a blood clot. Methods for sequestering a target molecule are also disclosed. The method includes reversibly coupling a target molecule to a nanoparticle having an affinity ligand that reversibly couples the target molecule, and thus, sequesters the target molecule activity until the target molecule interacts with its substrate resulting in the release of the target molecule.

Provided herein are tissue factor (TF)-targeted nanofibers and methods of treating hemorrhage in a subject therewith. In particular, peptide amphiphiles (PAs) are provided that comprise a TF-targeting peptide sequence and self-assemble under aqueous conditions into PA nanofibers displaying the TF-targeting sequence on the exterior of the nanofiber.

The invention relates to compositions including polynucleotides encoding polypeptides which have been chemically modified by replacing the uridines with 1-methyl-pseudouridine to improve one or more of the stability and/or clearance in tissues, receptor uptake and/or kinetics, cellular access by the compositions, engagement with translational machinery, mRNA half-life, translation efficiency, immune evasion, protein production capacity, secretion efficiency, accessibility to circulation, protein half-life and/or modulation of a cell's status, function, and/or activity.

A system for preparing a thrombin serum that can include a containment device, a cage received within the containment device, a cap attachable to the containment device, an inlet port configured to introduce a non-anti-coagulated autologous blood fluid into the containment device, and an outlet port. An activator, such as glass beads, can be present within the containment device.

Disclosed herein is an anti-adhesion kit comprised of: (i) a fibrinogen solution component comprising: fibrinogen at a concentration of about 5 to 25 mg/ml; and free calcium ions at a concentration ranging from 0.1 M to 1 mM; and (ii) a thrombin component containing thrombin. Further disclosed is an anti-adhesion kit comprised of: (i) a fibrinogen solution component containing fibrinogen at a concentration of 8% to 25% of total protein by weight, and optionally free calcium ions at a concentration ranging from 0.1 M to 1 mM; wherein a total protein concentration ranges from about 80 to 120 mg/ml; and (ii) a thrombin component containing thrombin. Methods of using the kits e.g., to provide anti-adhesion curable compositions are also disclosed.

Provided herein are kits comprised of a first container including a solution of fibrinogen-containing component that includes fibrinogen at a concentration range of about 5 mg/ml to about 30 mg/ml, and having a total protein concentration range of about 15 mg/ml to about 40 mg/ml; and a second container that includes a solution of thrombin-containing component. Further provided are mixtures comprised of fibrinogen and thrombin, calcium ions, and albumin, the mixture being comprised of total protein in a range of about 2.5 mg/ml to about 30 mg/ml, fibrinogen in a range of about 50% to about 80% of total protein, and albumin in a range of more than 0.65 mg/ml to about 3 mg/ml. Further provided herein are methods for preventing or reducing tissue adhesion, and hydrogel materials made of fibrin.