Pharmaceutical compositions comprising at least one lipid-based particle encapsulating a proteolytic enzyme and a pharmaceutically acceptable carrier, wherein the proteolytic enzyme comprises at least 75% proteolytically active enzyme are provided. Methods of using same and producing same are also provided.

An extrudable hydrogel composition useful for making a three-dimensional organ construct is described herein. Methods of using the same and products so made are also described. Also described herein is a multicellular organoid including at least two tumor cells or cell lines that are of the same tissue type, but are distinct from one another (e.g., distinct in morphology, growth rate, and/or at least one mutation); and at least one type of non-cancerous (i.e., normal or differentiated) tissue cells, wherein the at least one type of non-cancerous tissue cells are of the same tissue type as the at least two tumor cells or cell lines. In some embodiments, the at least two tumor cells or cell lines and/or the non-cancerous tissue cells are labeled with and/or comprise a detectable compound, optionally so that each of the different cells can be distinguished from each other (e.g., optically and/or electrically distinguished).

The present disclosure provides a delivery system comprising (i) a physiologically acceptable carrier and (ii) a proteolytic enzyme or effector thereof for use in a method for relaxing fibers within a subject's oral cavity. In some embodiments, the relaxation is for use in tooth manipulation (particularly repositioning). In some embodiments, the method involves the use of the proteolytic enzyme or effector thereof at a concentration effective to cause relaxation of fibers between the tooth's alveolar bone and gingiva while maintaining integrity of the fibers surrounding the tooth. Also disclosed herein are methods for fiber relaxation and/or repositioning of tooth making use of the proteolytic enzyme or effector thereof.

Fusion proteins containing active agonist or antagonist fragments of parathyroid hormone (PTH) and parathyroid hormone related peptide (PTHrP) coupled to a collagen-binding domain are presented. The fusion proteins can be used to promote bone growth, to promote hair growth, to prevent cancer metastasis to bone, to promote immune reconstitution with a bone marrow stem cell transplant, to promote mobilization of bone marrow stem cells for collection for autologous stem cell transplant, and to treat renal osteodystrophy. Pharmaceutical agents comprising a collagen-binding polypeptide segment linked to a non-peptidyl PTH/PTHrP receptor agonist or antagonist are also presented.

Described herein are formulations that can include one or more enzymes that can break down one or more components of scar tissue. Also provided herein are methods of treating scar tissue by administering a formulation provided herein to a subject in need thereof.

Provided herein are methods for evaluating tumor cell spheroids in a three-dimensional microfluidic device by determining changes in the relative levels of live cells and dead cells in aliquots cultured under different conditions. Methods described herein allow ex vivo recapitulation of the tumor microenvironment such that the in vivo effectiveness of a test compound in treating tumor tissue may be predicted.

The disclosure relates to the use of contact lenses for treating ophthalmologic conditions, such as presbyopia, induced myopia, computer vision syndrome, insufficient accommodation, or a condition associated with insufficient accommodation. The contact lens may be selected based on a measured sagittal depth and/or eccentricity of the cornea. When fitted, fluid may accumulate between the cornea of the eye and the contact lens The lens may exhibit a sufficient amount of apical clearance such that when the wearer blinks, the lens moves no more than 1 mm on the eye. The lens may be structured such that bubbles greater than 0.5 mm in diameter are prevented from forming between the contact lens and the eye. The contact lens may be used in combination with a suitable bioactive agent providing for enhanced visual correction.

A debridement enzyme for necrotic tissue is described that is not dependent upon proteolytic enzymatic activity but instead utilizes the amylase family of enzymes. The amylases (-, -, -amylase) are noted for the cleavage of the -glycosidic bonds of polysaccharides, yielding lower molecular weight carbohydrate/sugar fragments. It has now been found that -amylase is effective in the debridement of devitalized tissue.

Described herein are methods and compositions relating to methods of inhibiting neutrophils, e.g., inhibiting NET release or NETosis, by means of a DEspR inhibitor, e.g., an anti-DEspR antibody reagent. In some embodiments, the methods can relate to the treatment of a disease, e.g., cancer or a disease wherein neutrophils; NETs; or NETosing or NETting neutrophils contribute to pathogenesis, chronicity, or worsening of disease. In some embodiments, the DEspR inhibitor can be a bi-specific reagent or an antibody-drug conjugate.

Proteases regulate a wide range of normal cellular functions where dysregulated activity is observed in various diseases. Compositions and methods use protease activity multiplexed bead-based immunoassays to profile protease activity. This platform technology integrates protease activity measurements with total protein quantification techniques. It represents a significant improvement over existing detection techniques by allowing for multiplexed, sensitive active protease measurements in complex biological samples. Exemplary multiplexed detections are realized in a single assay using a minute sample amount (e.g., 5 l) for active recombinant MMP-1, -2, -3, -7, 9, and 12 and those same MMPs in cell culture supernatant, menstrual fluid effluent, and peritoneal aspirates. This multiplexed platform achieves high level of sensitivities equal to or better than existing leading single-plex detection strategies. It also allows for high throughput screening to identify inhibitors of proteases in complex, donor-derived samples.