Abstract: Methods of the disclosure provide an analytical pipeline for mapping activity in a disease-specific manner. Any of a variety of diseases or medical conditions may be mapped using the analytical pipeline. In preferred embodiments, the pipeline uses expression data (e.g., from RNA-Seq) to identify proteases that are active in disease tissue and subject to differential expression relative to normal tissue. A machine learning classifier selects a subset of the proteases that identify the disease with a threshold sensitivity and specificity, in which the subset is small enough that a corresponding set of protease substrates may be assembled into a nanoparticle activity sensor that, when administered to a patient, are cleaved in the presence of disease tissue to release detectable analytes signifying presence of the disease.

Abstract: The present disclosure provides patterned biomaterials having organized cords and extracellular matrix embedded in a 3D scaffold. According, the present disclosure is provides compositions and applications for patterned biomaterials. Pre-patterning of these biomaterials can lead to enhanced integration of these materials into host organisms, providing a strategy for enhancing the viability of engineered tissues by promoting vascularization.

Abstract: The present invention provides methods of inducing proliferation of and/or differentiating cells comprising contacting cells with compounds witin the methods of the invention. The present invention further provides cells obtainable by the methods of the invention.

Abstract: The present invention provides methods of inducing proliferation of and/or differentiating cells comprising contacting cells with compounds within the methods of the invention. The present invention further provides cells obtainable by the methods of the invention. Liver disease affects more than 500 million people worldwide. Organ transplantation is the gold standard for treatment of liver failure, but organ shortages are acute.

Abstract: Some embodiments described herein relate to cells which have been genetically engineered to release a polypeptide when a population of the cells reaches a desired density. In some embodiments, the released polypeptide may be a therapeutic polypeptide. In some embodiments, the therapeutic polypeptide kills tumor cells or which inhibits the growth of tumor cells.

Abstract: The invention provides for delivery, engineering and optimization of systems, methods, and compositions for manipulation of sequences and/or activities of target sequences. Provided are delivery systems and tissues or organ which are targeted as sites for delivery. Also provided are vectors and vector systems some of which encode one or more components of a CRISPR complex, as well as methods for the design and use of such vectors. Also provided are methods of directing CRISPR complex formation in eukaryotic cells to ensure enhanced specificity for target recognition and avoidance of toxicity and to edit or modify a target site in a genomic locus of interest to alter or improve the status of a disease or a condition.

Abstract: The present invention provides methods of inducing proliferation of and/or differentiating cells comprising contacting cells with compounds within the methods of the invention. The present invention further provides cells obtainable by the methods of the invention. Liver disease affects more than 500 million people worldwide. Organ transplantation is the gold standard for treatment of liver failure, but organ shortages are acute.

Abstract: A method of forming 3D engineered tissues by providing a 2D scaffold material comprising a plurality of fold locations and a plurality of cell assembly sites, assembling cells into the cell assembly sites and folding the 2D scaffold material along the fold locations to form a 3D scaffold structure. Tissues formed by the method.

Abstract: The present invention features assays for co-culturing primary cells while maintaining key biological activities specific to the primary cells. The invention is based, at least in part, on the discovery that compositions and methods for primary cells in a high-throughput co-culture platform, image analysis for distinguishing cells in co-cultures and assays that are suitable for screening of agents in epithelial cells, such as hepatocytes.

Abstract: The invention includes sensors and sensing methods for determining cell morphology and/or chemical composition of an analyte. A porous substrate exhibiting a first optical signal is exposed to a target analyte and subsequently monitored for changes in the optical signal. More specifically, a photonic or porous substrate having a well-defined and highly tunable reflectivity or transmission spectrum, such as porous silicon (Si), porous alumina, porous Ge, porous GaAs, porous SiO2 and porous polymer, is used for example. A porous or photonic substrate is exposed to an analyte, such as a cell or other macromolecule, and changes in the scattered light are observed over time to determine cell morphology and/or chemical composition of the analyte using the substrate.

Abstract: The invention is directed to methods for direct patterning of silicon. The invention provides the ability to fabricate complex surfaces in silicon with three dimensional features of high resolution and complex detail. The invention is suitable, for example, for use in soft lithography as embodiments of the invention can quickly create a master for use in soft lithography. In an embodiment of the invention, electrochemical etching of silicon, such as a silicon wafer, for example, is conducted while at least a portion of the silicon surface is exposed to an optical pattern. The etching creates porous silicon in the substrate, and removal of the porous silicon layer leaves a three-dimensional structure correlating to the optical pattern.

Abstract: The invention includes sensors and sensing methods for determining cell morphology and/or chemical composition of an analyte. A porous substrate exhibiting a first optical signal is exposed to a target analyte and subsequently monitored for changes in the optical signal. More specifically, a photonic or porous substrate having a well-defined and highly tunable reflectivity or transmission spectrum, such as porous silicon (Si), porous alumina, porous Ge, porous GaAs, porous SiO2 and porous polymer, is used for example. A porous or photonic substrate is exposed to an analyte, such as a cell or other macromolecule, and changes in the scattered light are observed over time to determine cell morphology and/or chemical composition of the analyte using the substrate.

Abstract: The disclosure provides an in vitro culture systems. The invention provides methods and systems useful for developing in vitro an engineered tissue, method of using the tissue and compositions comprising the tissue.

Abstract: The disclosure provides a bioreactor that allows steady-state oxygen gradients to be imposed upon in vitro culture systems. The bioreactor system of the disclosure has been applied to liver zonation and have shown that physiological oxygen gradients contribute to heterogeneity of tissue cultures in vitro.

Abstract: Provided is a microarray platform for the culture of cells atop combinatorial matrix mixtures; enabling the study of differentiation in response to a multitude of microenvironments in parallel.

Abstract: Provided are methods of the production of patterned 3-dimesional biopolymer scaffolds containing living cells. The methods include selective photopolymerization of biopolymers to create patterned structures and the patterning of cells within relatively homogenous slabs of biopolymer using dielectrophoresis. Also provided are patterned 3-dimensional biopolymer scaffolds generated by the methods and their use.

Abstract: The invention is directed to methods for direct patterning of silicon. The invention provides the ability to fabricate complex surfaces in silicon with three dimensional features of high resolution and complex detail. The invention is suitable, for example, for use in soft lithography as embodiments of the invention can quickly create a master for use in soft lithography. In an embodiment of the invention, electrochemical etching of silicon, such as a silicon wafer, for example, is conducted while at least a portion of the silicon surface is exposed to an optical pattern. The etching creates porous silicon in the substrate, and removal of the porous silicon layer leaves a three-dimensional structure correlating to the optical pattern.

Abstract: The invention is a series of soft lithographic methods for the microfabrication of biopoilymer scaffolds for use in tissue engineering and the development of artificial organs. The methods present a wide range of possibilities to construct two- and three-dimensional scaffolds with desired characteristics according to the final application. The methods utilize an elastomer mold which the biopolymer scaffold is cast. The methods allow for the rapid and inexpensive production of biopolymer scaffolds with limited specialized equipment and user expertise.

Abstract: Any of inorganic and bio-organic substances and molecules, and beads, pucks and like small things, that are both (i) electrically charged to a first polarity, and (ii) immersed in a fluid transport medium within (iii) an electrochemical cell, are assembled and patterned by action of moving these inorganic and bio-organic substances and molecules, etc. to a patterned electrode having an opposite, second, polarity under force of an applied electric field. The electrode patterned with conductive areas may be further, separately, patterned with chemicals, for example agarose gel, that chemically accept or reject the substances and molecules, etc., especially as are biological in origin. Living cells of plant, bacterial and animal types may be assembled. A semiconductor electrode may be patterned by masked laser light passed through the other electrode, which is transparent.

Abstract: Any of inorganic and bio-organic substances and molecules, and beads, pucks and like small things, that are both (i) electrically charged to a first polarity, and (ii) immersed in a fluid transport medium within (iii) an electrochemical cell, are assembled and patterned by action of moving these inorganic and bio-organic substances and molecules, etc. to a patterned electrode having an opposite, second, polarity under force of an applied electric field. The electrode patterned with conductive areas may be further, separately, patterned with chemicals, for example agarose gel, that chemically accept or reject the substances and molecules, etc., especially as are biological in origin. Living cells of plant, bacterial and animal types may be assembled. A semiconductor electrode may be patterned by masked laser light passed through the other electrode, which is transparent.