Abstract: Disclosed herein are novel peptide amphiphile molecules and compositions discovered to possess improved solubility in aqueous buffers which, in turn, facilitates purification required for pharmaceutical applications, particularly for in vivo administration to human patients. In addition, gels of such peptide amphiphile compositions are shown herein to possess unexpectedly superior gelation kinetics and rheological properties, including an increased mechanical stiffness, which better mimics the mechanical properties of natural central nervous system tissues.

Abstract: Provided herein are apparatuses, systems and methods for generating concentration gradients of soluble molecules. Also, provided herein devices and methods for generating in vitro blood vessels.

Abstract: A gel microdrop composition is provided. In certain embodiments, the gel microdrop composition contains a polymer matrix, an effector particle that releases an effector molecule into the polymer matrix, a first reporter particle that emits a first optically detectable signal and a second reporter particle that emits a second optically detectable signal that is distinguishable from the first optically detectable signal, where the effector particle and said first and second reporter particles are encapsulated by the polymer matrix. Methods of screening that employ the gel microdrop composition and methods of making the gel microdrop composition are also disclosed.

Abstract: The subject invention concerns a perfusion bioreactor device and methods of using the same. A bioreactor device of the invention can be used to grow cells and tissue in a controlled in vitro environment. A perfusion bioreactor device of the invention can have multiple perfusion chambers that can be controlled individually. Transverse or parallel flow of a fluid can be provided to each chamber. Cells can be seeded on a hydrogel and/or 3D scaffold to provide a 3D environment in the bioreactor device where the cells can adhere, proliferate, migrate, secrete growth and/or differentiation factors, and/or undergo differentiation, etc. The subject invention also concerns hydrogels and 3D scaffolds that can be used to grow and/or differentiate cells thereon.

Abstract: A method for creating networks of perfusable microvessels in vitro. A mandrel is drawn through a matrix to form a channel through the matrix. Cells are injected into the channel. The matrix is incubated to allow the cells to attach inside the channel. The channel is perfused to remove unattached cells to create a parent vessel, where the parent vessel includes a perfusable hollow channel lined with cells in the matrix. The parent vessel is induced to create sprouts into the surrounding matrix gel so as to form a microvessel network. The microvessel network is subjected to luminal perfusion through the parent vessel.

Abstract: Scaffold comprises a polymer defining macropores and comprising hydroxypropylcellulose partially substituted by a substituent comprising a self-crosslinkable group, which is crosslinked through the self-crosslinkable group. The macropores have an average pore size larger than 50 microns and are at least partially interconnected. In one method, bicontinuous emulsion comprising a continuous aqueous phase and a continuous polymer phase is formed. The polymer phase comprises hydroxypropylcellulose partially substituted by a substituent comprising a self-crosslinkable group, and is crosslinked through the self-crosslinkable group to form a polymer defining at least partially interconnected pores. In another method, phase separation is induced in a solution comprising a polymer precursor and water to form a bicontinuous emulsion comprising a continuous polymer phase and a continuous aqueous phase.

Abstract: This invention relates to protein fibrils, to methods and kits of producing those protein fibrils comprising a plurality of first peptide monomer units arranged in a first strand and a plurality of second peptide monomer units arranged in a second strand in which said first and second strands form an overlapping staggered heterodimer coiled coil structure, and wherein the amino acid residues on the exposed surface of said first and second strands enable said protein fibril to interact with another protein fibril in a plurality of non-parallel orientations. This invention also relates to bundles of protein fibrils and matrices, in particular, hydrogels produced using those protein fibrils.

Abstract: A hydrogel comprising a polysaccharide, wherein amphiphilic side chains are bonded to the carboxyl groups of a polysaccharide with carboxyl groups on side chains, an inorganic ion other than calcium ion, and water, and a method for its preparation. The gel has high viscoelasticity, can be injected into the body using an instrument such as a syringe, and is useful for various biomedical materials.

Abstract: The present invention provides a biocompatible, biodegradable graft composition for regeneration of neural tissue, comprising the following components: a) a gel scaffold formed from an isolated platelet containing fluid and an activating agent comprising calcium chloride, with or without thrombin, b) a nerve growth factor selected from BDNF, NGF, retinoic acid and combinations thereof, and c) a culture of at least 50,000 progenitor stem cells; the method of production and the uses thereof.

Abstract: A composite sorbent material is disclosed which comprises A) a housing of a dense, insoluble material having openings therein and B) a porous polymer gel housed within said housing, said housing being provided with openings therein for fluid communication between said porous monolithic polymer gel and the surroundings, and said porous monolithic polymer gel occupying the inner space of said housing and being kept on place within said housing by mechanical means. Processes for the preparation of composite sorbent materials by cryoprecipitation are also disclosed as well as the use of the composite sorbent material according to the invention e.g. for the removal of pollutants from gases or liquids, for the enrichment or separation of molecules and for cell culture.

Abstract: Disclosed is a method for production of recombinant human FSH in high yield and a high purity. The method comprises the steps of: (a) culturing recombinant human FSH-producing mammalian cells in a serum-free medium, (b) collecting culture supernatant, (c) subjecting the culture supernatant to cation-exchange column chromatography, (d) dye affinity column chromatography, (e) hydrophobic column chromatography, and (f) gel filtration column chromatography to collect recombinant human FSH-active fractions, in the order.

Abstract: The present disclosure provides hydrogel compositions having multiple gelation mechanisms. The composition includes at least one component which forms a hydrogel, in combination with a second component which includes a self-assembling peptide capable of forming a self-assembled macromer.

Abstract: Compositions and methods for creating a laminar construct for tissue-engineered dermal equivalent are provided. One composition provided herein comprises a hydrogel matrix comprising two or more hydrogels layers and a population of stem cells. Associated methods are also provided.

Abstract: A coated fiber for cell culture includes a fiber core having an exterior surface and a polymeric coating suitable for culturing cells disposed on at least a portion of the exterior surface of the fiber core. A polypeptide may be conjugated to the polymeric coating. A method for forming the coated fiber includes coating a polymer layer to an exterior surface of a fiber core to produce the coated fiber. The coating may occur as the fiber is being drawn.

Abstract: The present specification provides for methods for purifying fibroins, purified fibroins, methods of conjugating biological and synthetic molecules to fibroins, fibroins conjugated to such molecules, methods of making fibroin hydrogels, fibroin hydrogels and fibroin hydrogel formulations useful for a variety of medical uses, including, without limitation uses as bulking agents, tissue space fillers, templates for tissue reconstruction or regeneration, cell culture scaffolds for tissue engineering and for disease models, surface coating to improve medical device function, or drug delivery devices.

Abstract: Scaleable, vascularised tissue constructs that are composed of a multiplicity of cell containing, discrete and separable modules, methods of fabricating same and uses thereof. The tissue construct is a tissue substitute used in tissue transplantation or substitution or for the purpose of in vitro mimic of normal tissue.

Abstract: The present invention is directed to hydrogel compositions for biotechnology applications. Specifically, the invention provides hydrogels mimicking the ECM and uses thereof.

Abstract: A gel molding apparatus is adapted to be used in combination with a vessel that has a plurality of solution chambers, and includes a lid plate and a plurality of columns that project from a top surface of the lid plate. Each of the columns has a bottom side connected to the top surface of the lid plate, a top side opposite to the bottom side, and a well recessed from the top side for receiving a gel suspension and having a depth from the top side. A method for gel molding is conducted via the gel molding apparatus. A culture apparatus includes the vessel and the gel molding apparatus. A method for culture is performed through the culture apparatus.

Abstract: Slowly polymerizing polysaccharide hydrogels have been demonstrated to be useful as a means of delivering large numbers of isolated cells via injection. The gels promote engraftment and provide three dimensional templates for new cell growth. The resulting tissue is similar in composition and histology to naturally occurring tissue. This method can be used for a variety of reconstructive procedures, including custom molding of cell implants to reconstruct three dimensional tissue defects, as well as implantation of tissues generally.

Abstract: An implant for use in biological/biomedical applications may be prepared by subjecting a substrate to a gas-plasma treatment. The substrate may be a biocompatible material, including metals, ceramics, and polymers. More specifically, the substrate may be a bioresorbable polymer. The gas-plasma treatment may include subjecting the substrate to a plasma formed by a reactive gas. The gas-plasma treatment may be performed for a chosen duration at a radio frequency within a temperature range, a pressure range, and a supplied energy range. The substrate may be exposed to living cells, such that some of the living cells become coupled to the substrate. Gas-plasma treatment parameters may be chosen such that the living cells coupled to the treated substrate produce more of a cellular product than living cells coupled to an untreated substrate.

Abstract: The present invention provides a molecular marker for the identification of pluripotent pre-mesenchymal, pre-hematopoietic stem cells. The invention further provides primitive progenitor cells identified by the molecular marker. Such cells have the potential to differentiate into both mesenchymal and hematopoietic phenotypes, as determined by a proliferative response to inductive growth factors and cytokines, and by their morphologic and cytochemical features.

Abstract: The present invention provides novel metal alginates prepared from non-cross-linked alginate monomers such as sodium alginate and an aqueous solution of a group 4, 5, or 6 metal oxyhalide. The novel group 4, 5, and 6 metal alginates are useful in the preparation of cell culture supports, exhibit useful X-ray contrast properties, and exhibit unanticipated stability to standard autoclave conditions relative to known metal alginates such as calcium alginate. In general, the novel metal alginates provided by the present invention offer features and properties not observed in known metal alginates such as calcium or barium alginates.

Abstract: Described are packaged, sterile medical graft products containing controlled levels of a growth factor such as Fibroblast Growth Factor-2 (FGF-2). Also described are methods of manufacturing medical graft products wherein processing, including sterilization, is controlled and monitored to provide medical graft products having modulated, known levels of a extracellular matrix factor, such as a growth factor, e.g. FGF-2. Preferred graft materials are extracellular matrix materials isolated from human or animal donors, particularly submucosa-containing extracellular matrix materials. Further described are ECM compositions that are or are useful for preparing gels, and related methods for preparation and use.

Abstract: Provided are keratin compositions useful in cell culture. In some embodiments the keratins are biocompatible, promote cell growth, promote cell adhesion and provide an excellent substrate for cell culture. Keratin compositions described herein may be used as coatings, gels, three-dimensional scaffolds, additives to cell culture media, microcarriers, etc. The keratin substrates may also be used to deliver cells, e.g., for cell therapy applications.

Abstract: Imaging specimen such as biological tissue is facilitated. According to an example embodiment of the present invention, a relatively thin, surface portion of a specimen is stained and imaged. The thin portion is removed, exposing a new portion of the specimen. The newly-exposed portion is stained and imaged. Subsequent new surface portions (newly exposed) are similarly stained and imaged, with multiple images obtained from the specimen in an automated fashion. Some applications are directed to the distinct imaging of specimen characteristics having relatively small vertical separation (e.g., less than about 40 nanometers), with an upper characteristic imaged, removed, and the lower characteristic subsequently imaged.

Abstract: This disclosure relates to cell culture surfaces derived from or contain gums including naturally occurring gums, plant gums, galactomannan gums or derivatives thereof including carboxyalkyl guar gum. Even more particularly, the disclosure relates to chemically or physically cross-linked modified gums where the gum surfaces are tuned to provide cell culture surfaces with physical and chemical characteristics particularly suited for hepatocyte culture. The disclosure also relates to articles of manufacture (e.g., cell culture vessels and labware) having such matrices, methods of making and providing the matrices to cell culture surfaces, and methods of using cell culture vessels having such matrices.

Abstract: The instant invention is directed to a tissue engineered intervertebral disc comprising at least one inner layer and an exterior layer, wherein: the exterior layer comprises a nanofibrous polymer support comprising one or more polymer nanofibers; the at least one inner layer comprises a hydrogel composition comprising at least one or more hydrogel materials and/or one or more polymer nanofibers; and a plurality of cells which are dispersed throughout the tissue engineered intervertebral disc. Additionally, the instant invention is directed to methods of making such intervertebral discs and methods of treating intervertebral disc damage.

Abstract: A cell culture apparatus and a method for fabricating the cell culture apparatus are disclosed, the method comprises forming at least one fillister on a biomaterial composite layer by photolithography, wherein the biomaterial composite layer contains two gel materials. One is a bio-compatible hydrogel composition having various weight ratio of: 2-hydroxyethylmathacrylate (HEMA), bisphenolA and glycidyl methacrylate (bis-GMA), triethylene glycol dimethacrylate (TEGDMA), r-methacryloxypropyl trimethoxysilane (MAPTMS), ?,?-diethoxyacetophenone (DEAP), and the other one is a photo-sensitive silica gel composition.

Abstract: This invention relates to biomaterials for directional tissue growth which comprise soluble fibres having a variable cross-sectional area which dissolve in a directional manner in situ, thereby controlling the direction and rate of formation of microchannels within the biomaterial and allowing vectored and timed channelling through the biomaterial. This may be useful, for example in directing the growth of blood vessels, nerves and other repair cells through the biomaterial in defined directions.

Abstract: A device, and method of making the device, capable of therapeutic treatment and/or for in vitro testing of human skin. The device may be used on skin wounds for burned, injured, or diseased skin, and provides structures and functions as in normal uninjured skin, such as barrier function, which is a definitive property of normal skin. The device contains cultured dermal and epidermal cells on a biocompatible, biodegradable reticulated matrix. All or part of the cells may be autologous, from the recipient of the cultured skin device, which advantageously eliminates concerns of tissue compatibility. The cells may also be modified genetically to provide one or more factors to facilitate healing of the engrafted skin replacement, such as an angiogenic factor to stimulate growth of blood vessels.

Abstract: The present invention relates to a tissue-engineered scaffold prepared by using a biocompatible and injectable hydrogel, and particularly to a tissue-engineered scaffold capable of regenerating or recovering an injured spinal nerve for central nervous system after being implanted to connect neurons, prepared by combining an adult stem cell or a nerve cell with a physiologically active material on tissue-engineered carriers comprising biocompatible and temperature-sensitive polyethylene glycol/polyester block copolymer or biocompatible and injectable hydrogel made of small intestinal submucosa tissue powder with sol-gel phase transition behavior.

Abstract: Implants for resurfacing or repairing one or more articular cartilage bearing surfaces of a biological organism include an engineered tissue and a biocompatible porous substrate secured to the engineered tissue for attaching the implant to a native bone of the biological organism. The engineered tissue includes a scaffold containing a biocompatible material, and a plurality of living chondrocytes supported by the scaffold. Methods for culturing chondrocytes for incorporation into a biocompatible implant are provided. A bioreactor for producing functional cartilaginous tissue from a cell-seeded scaffold and a system for producing functional cartilaginous tissue are also provided.

Abstract: The present invention relates to a process for making a gel comprising combining a silanol species comprising at least two silanol groups per molecule and a hydrophilic hydroxyl species comprising at least two hydroxyl groups per molecule. The gel is capable of being converted to a liquid by application of a mechanical shear force and the liquid is capable of being converted to the gel in the absence of said mechanical shear force.

Abstract: The present invention relates to methods for cultivating dermal fibroblasts, methods for preparing in vitro dermis equivalents, methods for preparing three-dimensional in vitro skin equivalents, an in vitro dermis equivalent, a three-dimensional in vitro skin equivalent, and methods for determining the effect of a chemical substance or of an agent on human skin cells using the in vitro dermis equivalent and/or the in vitro skin equivalent.

Abstract: Microvessel networks are produced in vitro from tissue-engineered parent vessels sprouting into a supporting matrix, as for example gels, of extracellular matrix proteins. The microvessel systems are integrated into devices that allow for controlled perfusion with fluids. The vessels may include cells from one cell type, for example, endothelial cells, or from combinations of two or more cell types.

Abstract: A modified reconstituted extracellular matrix composition is provided herein. The composition includes an extracellular matrix and at least one exogenous component selected from heparin, fibronectin and laminin. The composition may have a basic pH. Additionally, provided herein is a cell culturing system including a substrate and a coating thereon of the composition to assess potential stimulators and/or inhibitors for their effects on various cell cultures while increasing the signal dynamic range.

Abstract: Cell culture scaffolds presenting a more biologically relevant microenvironment are disclosed. More particularly, these cell culture scaffolds comprise three-dimensional matrices/biomaterials that are created from solubilized collagen compositions using controlled conditions to have the desired microstructure and mechanical properties. The engineered purified collagen based matrix compositions of the present invention can be used alone or in combination with cells as a tissue graft construct to enhance the repair of damaged or diseased tissues.

Abstract: The present invention provides a self-assembling peptide comprising: (a) a first amino acid domain that mediates self-assembly, wherein the domain comprises alternating hydrophobic and hydrophilic amino acids that are complementary and structurally compatible and self-assemble into a macroscopic structure when present in unmodified form; and (b) a second amino acid domain that does not mediate self-assembly in isolated form, wherein the second amino acid domain comprises at least one minimal biologically active sequence. Such self-assembling peptides are described herein as “modified self-assembling peptides.” The present invention also provides pharmaceutical compositions, kits and matrices comprising a modified self-assembling peptide, and methods of using and making such compositions, kits and matrices.

Abstract: Apparatuses, systems, and methods are provided for growing and maintaining cells. A three-dimensional matrix, such as a hydrogel material, is seeded with cells and placed in a bioreactor having two compartments. The matrix is supported between the two compartments by first and second porous materials, which engage opposing surfaces of the matrix. A first media stream having certain properties is propagated through the first compartment, where it contacts one surface of the matrix via the first porous material. A second media stream having different properties is propagated through the second compartment such that it contacts the opposite surface of the matrix via the second porous material. Through migration of each stream at least partially into the matrix, various controlled gradients may be established within the matrix, encouraging growth of the cells. Such gradients include osmotic pressure, oscillating osmotic pressure, hydrostatic pressure, oxygen tension, and/or nutrient gradients.

Abstract: Methods for inducing differentiation of dermis-derived cells to serve as a source of chondrocytes and associated methods of use in forming tissue engineered constructs. One example of a method is a method for inducing differentiation of cells into chondrocytes comprising providing aggrecan sensitive isolated dermis cells and seeding the cells onto an aggrecan coated surface.

Abstract: Methods for forming tissue engineered constructs without the use of scaffolds and associated methods of use in tissue replacement. One example of a method may comprise providing a shaped hydrogel negative mold; seeding the mold with cells; allowing the cells to self-assemble in the mold to form a tissue engineered construct.

Abstract: Method of providing a substrate with a ready-to-use uniformly distributed extracellular matrix is disclosed. This method includes applying extracellular matrix components to a substrate area; incubating the extracellular matrix components to allow polymerization thereof; freezing the polymerized extracellular matrix on the substrate area; lyophilizing the frozen extracellular matrix on the substrate area; and allowing the lyophilized extracellular matrix to warm to room temperature. Also contemplated is a cell culture apparatus having a dried uniformly distributed extracellular matrix formed by the above-mentioned method.

Abstract: A culture method for allowing only cancer cells to grow from a cancerous organ or tissue sample removed surgically or endoscopically, forming a spheroid of cancer cells having a tissue structure and different cell stages similar to a tissue structure and cell stages in the living body, and removing the cultured spheroid of cancer cells from the matrix by changing the temperature within the physiological temperature range.

Abstract: To provide a new reductive-stimuli-responsive degradable gel that allows any control of decomposition of the three-dimensional base material for cell culture and production of a completely biological three-dimensional cellular structure consisting only of cells and cells-produced extracellular matrix and that allows safe recovery of the cellular structure produced. A stimuli-responsive hydrogel, characterized by being produced by crosslinking a water-soluble polymer with a compound having a disulfide bond in the molecular chain.

Abstract: A cell culture scaffold containing a gel having a network structure comprised of a synthetic polymer such that cultured cells spread in a shorter time and the number of adsorbed cultured cells per unit area is larger than in the case of using a gel having a network structure comprised of polyacrylic acid, while taking advantage of synthetic polymers with low manufacturing cost, easy quality control and no risk of virus infection in cultured cell. Used as the cell culture scaffold is a gel containing a synthetic polymer obtained by polymerization or copolymerization of a monomer having a sulfonic group such as p-styrenesulfonic acid sodium salt (NaSS) and 2-acrylamide-2-methylpropane sulfonic acid sodium salt (NaAMPS).

Abstract: An artificial extra cellular matrix product and artificial human and animal tissue product comprising tissue specific cells.

Abstract: An apparatus and method of using the apparatus to prepare a biocompatible biodegradable matrix capable of supporting cells to form an implantable or engraftable surgical device. A matrix-forming fluid is contained within a chamber defined by top and bottom surfaces of a thermally conductive material and spacers defining the thickness of the matrix. The chamber is then cooled to freeze the solution at a controlled rate, resulting in a matrix with a desired and uniform thickness having symmetric and uniform reticulations. The apparatus and method reproducibly forms such a matrix, which may be populated with cells for transplantation and engraftment into a wound.

Abstract: A cell culture scaffold containing a gel having a network structure comprised of a synthetic polymer such that cultured cells spread in a shorter time and the number of adsorbed cultured cells per unit area is larger than in the case of using a gel having a network structure comprised of polyacrylic acid, while taking advantage of synthetic polymers with low manufacturing cost, easy quality control and no risk of virus infection in cultured cell. Used as the cell culture scaffold is a gel containing asynthetic polymer obtained by polymerization or copolymerization of a monomer having a sulfonic group such as p-styrenesulfonic acid sodium salt (NaSS) and 2-acrylamide-2-methylpropane sulfonic acid sodium salt (NaAMPS).

Abstract: A method for production of artificial skin by administering matrix metalloproteinase inhibitor or matrix metalloproteinase inhibitor and matrix protein production promoting agent. The matrix metalloproteinase inhibitor is N-hydroxy-2(R)-[[(4-methoxyphenyl)sulfonyl](3-picolyl)amino]-3-methylbutanamide hydrochloride.

Abstract: Biological agents such as secretory cells are encapsulated in a hydrophilic gel made of agarose or collagen-agarose and gelatin sponge-agarose combinations. In a preferred embodiment, semi-solid beads are formed from a suspension containing collagen, agarose and secretory cells such as pancreatic islets, the collagen is polymerized to form solid, agarose-collagen beads and the solid beads are coated with agarose. Coating is preferably by rolling the solid beads in about 5-10% agarose, contacting the rolled beads with mineral oil and washing oil from the beads. Beads containing secretory cells can be transplanted into a mammal to treat a condition caused by impaired secretory cell function.