Abstract: Synthetic hydrogels for organogenesis support organogenesis from mammalian cells, including human cells. The synthetic hydrogels typically include a network of crosslinked branched biodegradable polymers. A portion of the branches of the branched biodegradable polymers are linked to binders which are generally synthetic peptides for cell and extracellular matrix attachment. The hydrogels may include an inhibitor of apoptosis. The synthetic hydrogels with the synthetic binders typically do not interfere with cellular, proteomic, genetic, and/or transcriptome analyses of organoids formed in the hydrogel. The synthetic hydrogels may be subject to on-demand dissolution to provide intact organoids substantially free of hydrogel polymers. Also provided are methods of making the synthetic hydrogels and methods of using the synthetic hydrogels for organogenesis.

Abstract: A flow control system that produces smooth flow for on-chip pneumatic micropumps has been developed. By establishing a flow control system that can achieve smooth flow, fluidic conditions of microphysiological systems can be controlled to accurately mimic biological conditions. Biological experiments can require flow profiles anywhere on the spectrum of smooth flow to highly pulsatile flow. A smooth flow profile can be modified with pumping delays to make the flow profile as pulsatile as desired.

Abstract: 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.

Abstract: Synthetic hydrogels for organogenesis support organogenesis from mammalian cells, including human cells. The synthetic hydrogels typically include a network of crosslinked branched biodegradable polymers. A portion of the branches of the branched biodegradable polymers are linked to binders which are generally synthetic peptides for cell and extracellular matrix attachment. The hydrogels may include an inhibitor of apoptosis. The synthetic hydrogels with the synthetic binders typically do not interfere with cellular, proteomic, genetic, and/or transcriptome analyses of organoids formed in the hydrogel. The synthetic hydrogels may be subject to on-demand dissolution to provide intact organoids substantially free of hydrogel polymers. Also provided are methods of making the synthetic hydrogels and methods of using the synthetic hydrogels for organogenesis.

Abstract: The invention is directed to a composition comprising all or a portion of a beta-tricalcium phosphate (?-TCP) bound to all or a portion of a ?-TCP binding peptide and methods of use thereof.

Abstract: The invention is directed to a composition comprising all or a portion of a beta-tricalcium phosphate (?-TCP) bound to all or a portion of a ?-TCP binding peptide and methods of use thereof.

Abstract: A device for controlling apical flow to a cell culture includes an apical insert that defines at least one inlet channel extending from an inlet port to an apical feed port and at least one outlet channel extending from an apical effluent port to an outlet port. The apical insert includes a projecting portion configured to extend into a cell culture insert to a depth that is less than a depth of the cell culture insert, and a contact surface configured to maintain a spatial relationship between the projecting portion and the cell culture insert.

Abstract: 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.

Abstract: Fluidic multiwell bioreactors are provided as a microphysiological platform for in vitro investigation of multi-organ crosstalks with microbiome for an extended period of time of at least weeks and months. The platform has one or more improvements over existing bioreactors, including on-board pumping for pneumatically driven fluid flow, a redesigned spillway for self-leveling from source to sink, a non-contact built-in fluid level sensing device, precise control on fluid flow profile and partitioning, and facile reconfigurations such as daisy chaining and multilayer stacking. The platform supports the culture of multiple organs together with microbiome in a microphysiological, interacted systems, suitable for a wide range of biomedical applications including systemic toxicity studies and physiology-based pharmacokinetic and pharmacodynamic predictions. A process to fabricate the bioreactors is also provided.

Abstract: Methods, compounds and kits relating to treating cancer, reducing kinase inhibitor or resistance, and reducing or preventing diminished ectodomain shedding are described.

Abstract: Methods of forming, dissolving, and functionalizing an extracellular matrix gel on demand based on cross-linking, modification, and dissolution of hydrogels using transpeptidase (e.g. sortase) are disclosed. Also provided are hydrogels comprising one or more macromers crosslinked to a mixture of peptides, wherein all or a portion of the peptides in the mixture comprise a recognition motif cleavable by a transpeptidase (e.g., sortase).

Abstract: A device for controlling apical flow to a cell culture includes an apical insert that defines at least one inlet channel extending from an inlet port to an apical feed port and at least one outlet channel extending from an apical effluent port to an outlet port. The apical insert includes a projecting portion configured to extend into a cell culture insert to a depth that is less than a depth of the cell culture insert, and a contact surface configured to maintain a spatial relationship between the projecting portion and the cell culture insert.

Abstract: Methods, compounds and kits relating to treating cancer, reducing kinase inhibitor or resistance, and reducing or preventing diminished ectodomain shedding are described.

Abstract: The invention provides methods and compositions for reducing, preventing or reversing cardio toxicity side effects associated with certain therapeutic agents. The invention also provides methods and compositions for treating heart dysfunction including heart failure, and for reversing the effects of myocardial infarction. The various aspects of the invention involve the use of ligand dimers, such as neuregulin dimers, that selectively induce the dimerization of certain EGF receptors in cardiac tissue.

Abstract: Provided herein are ligand dimers, compositions thereof, as well as methods of their use. The ligand dimers provided can comprise at least one ligand to a Her receptor and can be used to force dimerization of specific receptor pairs. The forced dimerization of specific receptor pairs can be used to control (e.g., promote or inhibit) signaling, and, therefore, the ligand dimers provided can also be used in various forms of treatment in which such signaling control is beneficial to a subject. It follows that methods for controlling signaling are provided as are various methods of treatment.

Abstract: The invention provides methods and compositions for reducing, preventing or reversing cardio toxicity side effects associated with certain therapeutic agents. The invention also provides methods and compositions for treating heart dysfunction including heart failure, and for reversing the effects of myocardial infarction. The various aspects of the invention involve the use of ligand dimers, such as neuregulin dimers, that selectively induce the dimerization of certain EGF receptors in cardiac tissue.

Abstract: The invention is directed to a composition comprising all or a portion of a beta-tricalcium phosphate (?-TCP) bound to all or a portion of a ?-TCP binding peptide and methods of use thereof.

Abstract: The invention provides methods and compositions for reducing, preventing or reversing cardio toxicity side effects associated with certain therapeutic agents. The invention also provides methods and compositions for treating heart dysfunction including heart failure, and for reversing the effects of myocardial infarction. The various aspects of the invention involve the use of ligand dimers, such as neuregulin dimers, that selectively induce the dimerization of certain EGF receptors in cardiac tissue.

Abstract: A system has been constructed that recapitulate the features of a capillary bed through normal human tissue. The system facilitates perfusion of three-dimensional (3D) cell monocultures and heterotypic cell co-cultures at the length scale of the capillary bed. A major feature is that the system can be utilized within a “multiwell plate” format amenable to high-throughput assays compatible with the type of robotics commonly used in pharmaceutical development. The system provides a means to conduct assays for toxicology and metabolism and as a model for human diseases such as hepatic diseases, including hepatitis, exposure-related pathologies, and cancer. Cancer applications include primary liver cancer as well as metastases. The system can also be used as a means of testing gene therapy approaches for treating disease and inborn genetic defects.

Abstract: Provided herein are ligand dimers, compositions thereof, as well as methods of their use. The ligand dimers provided can comprise at least one ligand to a Her receptor and can be used to force dimerization of specific receptor pairs. The forced dimerization of specific receptor pairs can be used to control (e.g., promote or inhibit) signaling, and, therefore, the ligand dimers provided can also be used in various forms of treatment in which such signaling control is beneficial to a subject. It follows that methods for controlling signaling are provided as are various methods of treatment.