Abstract: The present invention relates generally to the field of cell culture, which is a laboratory process used primarily for the growth, propagation, and production of cells for analysis and the production and harvesting of cell products. The present invention comprises functionalized and/or engineered hydrogel microcarriers that exhibit any or all of the following properties: controllable buoyancy, ferro- or paramagnetism, molecular or fabricated reporting elements, and optical clarity. The microcarriers are used in a bioreactor that employs external forces to control said microcarrier kinetic energy and translational or positional orientation in order to facilitate cell growth and/or cellular analysis. The bioreactor can be part of an automated system that employs any or all of the following; a microcarrier manufacturing method, a monitoring method, a cell culture method, and an analytical method.

Abstract: Three-dimensional biomimetic tissue scaffolds, as well as methods of manufacture of these scaffolds. The method is fully customizable to create a biomimetic tissue scaffold with shapes, densities, and geometries similar or identical to the tissue it imitates. For example, physiologically realistic collagen/PEG villi created using the method are designed to have a high-aspect ratio and curvature similar to villi found in the human small intestine. Accordingly, the biomimetic tissue scaffolds serve as an improved in vitro model for a wide variety of physiological research, as well as pharmacological testing and drug, compound, and/or metabolite uptake by cells growing on the scaffold, among many other uses.

Abstract: The present invention relates to biocompatible, biodegradable polyurethane/urea polymeric compositions that are capable of in-vivo curing with low heat generation to form materials suitable for use in scaffolds in tissue engineering applications such as bone and cartilage repair. The polymers are desirably flowable and injectable and can support living biological components to aid in the healing process. They may be cured ex-vivo for invasive surgical repair methods, or alternatively utilized for relatively non-invasive surgical repair methods such as by arthroscope. The invention also relates to prepolymers useful in the preparation of the polymeric compositions, and to methods of treatment of damaged tissue using the polymers of the invention.

Abstract: The present invention provides for scaffolds for growing RPE cells, comprising two or more biodegradable polymers. The present invention also provides for methods for creating a scaffold for growing RPE cells. Additionally, the present invention provides for RGD peptide linked polymer scaffolds for supporting the growth of RPE cells. The present invention provides methods of culturing RPE cells using the scaffolds produced herein. The present invention also provides methods of treating vision loss through the administration of RPE cell attached RGD peptide linked polymer scaffolds produced herein. The present invention further provides kits for treating vision loss.

Abstract: A method is provided for the preparation of a poly(amic acid) in which ring opening polymerization is employed to react the monomers ethylenediaminetetraacetic dianhydride and paraphenylenediamine in an aprotic solvent. The resulting poly(amic acid) composition is suitable as a biocompatible material, such as a biomedical implant, implant coating material, tissue scaffold material, controlled release drug delivery vehicle, and cellular growth substrate.

Abstract: A membrane which can be used for cultivating cells, in particular adherent cells. The membrane permits the adhesion and proliferation of the cells based on its specific composition comprising polyurethane. The resulting surface characteristics further permit the membrane to be used without any pre-treatment with surface modifying substances. A method for preparing a membrane which can be used for cultivating cells, in particular adherent cells. Methods of using the membrane for cultivating cells, in particular adherent cells.

Abstract: Polyester compositions and functionalized polyester compositions are provided along with methods of making the compositions as well as methods of using the compositions, for example as a tissue engineering bioscaffold and as a drug-delivery vehicle.

Abstract: Methods and kits of releasing cells are provided. The method comprises the steps of providing cultured cells on a cell culture support comprising a multi layer polyelectrolyte coating immobilized on a substrate, and releasing the cultured cells from the cell culture support by a releasing solution comprising DMSO. The kit comprises a cell culture support and a releasing solution. The releasing solution comprises DMSO.

Abstract: A peptide cross-linking agent in the form of a linear molecule has a molecular mass of 3 to approximately 60 kDa. The peptide cross-linking agents are used for cross-linking functionalized polymers to form hydrogels having two or more components.

Abstract: Thermoplastic polymeric sheets are rendered microporous and remain substantially flat by contacting the sheet with a first fluid composition that contains or more solvents for the polymeric sheet to render the sheet microporous and then contacting the microporous sheet with a second fluid composition that is substantially free of solvents for the polymer and that contains a non-solvent that is miscible with the one or more solvents of the first composition. Contacting the microporous sheet with the second fluid composition preferably occurs prior to substantial evaporation of the first fluid compositions, or solvents thereof, from the microporous sheet.

Abstract: A process to facilitate growing of cells on a nanotextured percutaneous portal is provided that includes the placement of a nanotextured percutaneous portal partially within a subject. A vacuum manifold is secured to the nanotextured percutaneous portal. Upon coupling the vacuum manifold to a vacuum source, the growth of the cells is facilitated.

Abstract: The invention relates to methods for assisted reproduction technology in mammals. Specifically the invention relates to methods for in vitro mammalian oocyte culture and oocyte maturation, in vitro fertilization, and in vitro embryo development.

Abstract: Cell culture substrates are provided. Aspects of the cell culture substrate include a substrate with a surface having at least one hydrophilic region and at least one hydrophobic region, and a surfactant layer present on the surface of the substrate and configured to produce a cell-binding surface on the hydrophilic regions of the surface. Also provided are kits which include the cell culture substrate, as well as methods of producing the cell culture substrate. The cell culture substrate and methods described herein find use in a variety of applications, including single-cell culture applications.

Abstract: A substrate (10), in particular for receiving biological cells (21) comprises a substrate body (1) which has a support area (2) on which there are fixed thermoreactive microgels (3) which comprise particles containing a thermoreactive polymer. Also described are a process for the preparation of the substrate (10) and a method for culturing biological cells (21) on the substrate (10).

Abstract: Biocompatible hydrogels made from cross-linked catechol-borate ester polymers are disclosed, along with methods of synthesizing and using such hydrogels. The hydrogels of the present invention are prepared by boronic acid-catechol complexation between catechol-containing macromonomers and boronic acid-containing cross-linkers. The resulting hydrogels are pH-responsive and self-healing, and can be used in a number of different biomedical applications, including in surgical implants, in surgical adhesives, and in drug delivery systems is data provides further evidence of the viability of using the disclosed hydrogels for in vivo in biomedical applications.

Abstract: Stacked, lamellar constructs comprised of, synthetic or natural, polymeric membrane structures which are brought together to form 3D scaffolds for biomaterial and guided tissue engineering applications have been developed. Each layer can have 2D or 3D nano and micro topographical features similar to or different than each other which can be arranged during the construction of each lamellae and their orientation can be adjusted during construction phase of the 3D structure. Such a construct was utilized in the development of an artificial cornea with human primary cells, in which patterned surface of the components of the lamellar structure mimics the oriented collagen structure inherent in natural cornea. Similar exploitation of the 3D patterned structure can be made for tissues where aligned ECM architecture is crucial, such as ligaments, bone, tendon, skin.

Abstract: The present invention aims to provide an artificial tissue that can efficiently reproduce myocardial tissue function and that can be used in an actual implantation and produced by culturing. The present invention relates to a graft material for treating myocardial disease, the graft material including a cell sheet containing adipocytes.

Abstract: The present invention relates in one aspect to a method for determining the cell culture history of a cell unit labelled with more than one type of tag comprising the steps of: (a) measuring one or more parameters of each tag that is used to label the cell unit; (b) identifying each tag in the cell unit; and (c) correlating the identity of each tag to the identity of the cell unit and/or the specific cell culture conditions to which the cell unit has been exposed.

Abstract: A method for preparing a porous-three-dimensional scaffold good for tissue engineering is described. Sericin forms a three-dimensional scaffold with PVA after freeze-drying having glycerin as a plasticizer and genipin as natural crosslinking agent to help making a strong and stable matrix. Adding glycerin into scaffold gives good uniformity and porosity. Smaller pore sizes and better uniformity are obtained as the concentration of genipin in the scaffold increases. Glycerin retains a high moisture content to allow the presence of water molecule in the matrix structure. Adding genipin results in a higher degree of crosslinking within the scaffold. Crosslinking using genipin is most beneficial in preparing scaffold possesses the best biological and physical properties for wound healing. The present invention describes method for preparing crosslinked matrix whose composition can be appropriately tuned to obtain matrix with desirable characteristics for biological applications.

Abstract: A cell culture article including a substrate having nanoparticles on the substrate surface, the nanoparticle including: a polymer of formula (I) where (x), (y), (z), R, R?, R?, S, W, and X, are as defined herein. Methods for making the cell culture article or cell culture article and methods for performing an assay of a ligand with the article are also disclosed.

Abstract: A composition for forming a polymeric cell culture surface includes (i) a pre-polymer comprising a polymer backbone, a cationic moiety conjugated to the backbone, and a cross-linker moiety conjugated to the backbone; and (ii) a peptide-polymer comprising a polymer backbone and cell adhesive peptide conjugated to the backbone. Cross-linked coatings for cell culture that have a suitable amount of cell adhesive peptide and cationic moiety may be formed from the pre-polymer and peptide-polymer.

Abstract: The invention relates to an immobilized preparation of a cell adhesion protein or peptide for cell culture having a hydrophobic cell culture substrate, a cell adhesion protein or peptide and a hydrophobic binding-adsorptive polymer to which the cell adhesion protein or peptide has been covalently bound. The hydrophobic binding-adsorptive polymer to which the cell adhesion protein or peptide is covalently bound is adsorbed to the hydrophobic cell culture substrate by hydrophobic binding and not by chemical bonding. The hydrophobic binding-adsorptive polymer is a copolymer of maleic anhydride and styrene, a copolymer of maleic anhydride and butyl vinyl ether or a copolymer of maleic anhydride and hexyl vinyl ether.

Abstract: Synthetic surfaces suitable for culturing stem cell derived cardiomyocytes contain acrylate polymers formed from one or more acrylate monomers. The acrylate surfaces, in many cases, are suitable for culturing stem cell derived cardiomyocytes in chemically defined media.

Abstract: In a process of forming a hydrogel from a mixture comprising hydrogen peroxide (H2O2), horseradish peroxidase (HRP), and a polymer comprising a crosslinkable phenol group, the gelation rate in the solution and the crosslinking density in the hydrogel can be independently adjusted or controlled by selection of the molarity of H2O2 and concentration of HRP in the solution when the molarity of H2O2 is limited to be within a range and the concentration of HRP is limited to be above a threshold. A method for determining the range and threshold is disclosed. The hydrogel may be used to grow cells, in which case, the molarity of H2O2 may be selected to affect the differentiation or growth rate of the cells in the hydrogel.

Abstract: A tissue engineering scaffold for growing cells can include a plurality of biocompatible microspheres linked together to form a three-dimensional matrix. The matrix can include a plurality of pores for growing cells. The biocompatible microspheres can include first and second sets of microspheres. The first set of microspheres can have a first characteristic, and a first predetermined spatial distribution with respect to the three-dimensional matrix. The second set of microspheres can have a second characteristic that is different from the first characteristic, and a second predetermined spatial distribution that is different from the first predetermined spatial distribution with respect to the three-dimensional matrix.

Abstract: The present invention relates to a process for preparation of a biodegradable polymer scaffold using biodegradable polymer, surfactant and alcohol. The biodegradable polymer scaffold obtained from the process disclosed is useful for tissue engineering, therapeutic compound delivery and/or wound dressing.

Abstract: This disclosure relates to temperature-responsive co-polymers, such as poly(N-isopropylacrylamide-co-hydroxypropyl methacrylate-co-3-trimethoxysilypropyl methacrylate). The disclosure also relates to polymeric films formed from these co-polymers and particular applications of these polymeric films, particularly in the cell culture field. More specifically, the present disclosure relates to the use of these polymeric films in the cell culture field to provide a means of controlling cellular adhesion to, and detachment from, the surface of a cell culture support substrate.

Abstract: Synthetic surfaces suitable for culturing stem cell derived cardiomyocytes contain acrylate polymers formed from one or more acrylate monomers. The acrylate surfaces, in many cases, are suitable for culturing stem cell derived cardiomyocytes in chemically defined media.

Abstract: The invention concerns macromers, having a molecular weight of at least 2 kDa, comprising at least one unit of the formula P-(protein-P)n, wherein: P is selected from polyethylene glycol (PEG), alginate, polyurethane, and polyvinyl alcohol; protein comprises at least one bis-cysteine matrix metalloproteinase (MMP)-sensitive peptide; and n is an integer from 2 to 500. Other aspects of the invention concern hydrogels utilizing cross-linked macromers and methods of producing such macromers and hydrogels.

Abstract: The present invention relates to a controllable polymeric surface coating including a macromolecule, which is covalently bound to the surface of a substrate, the macromolecule including a plurality of polymerisation initiators and a plurality of surface binding groups. Pendant polymers may be grafted from at least some of the polymerisation initiators.

Abstract: A method of surface modification of a biocompatible, biodegradable polymer substrate using RF plasma treatment is disclosed. This method and the resulting surface provide for enhanced adhesion and proliferation of cells, such as hKDCs, and can be used with scaffolds for tissue regeneration and with other delivery vehicles such as medical devices.

Abstract: The invention features compositions comprising agents having cardiac protective activity isolated from epicardial progenitor cells and derivatives thereof, and methods for the use of such compositions.

Abstract: Provided are novel biocompatible copolymers and compositions comprising the copolymers. The copolymers are non-toxic and typically have an LCST below 37° C. Compositions comprising the copolymers can be used for wound treatment, as a cellular growth matrix or niche and for injection into cardiac tissue to repair and mechanically support damaged tissue. The copolymers comprise numerous ester linkages so that the copolymers are erodeable in situ. Degradation products of the copolymers are soluble and non-toxic. The copolymers can be amine-reactive so that they can conjugate with proteins, such as collagen. Active ingredients, such as drugs, can be incorporated into compositions comprising the copolymers.

Abstract: Provided is a temperature-responsive cell culture substrate. A non-crosslinked temperature-responsive polymer having a molecular weight between 10,000 and 150,000 is immobilized on the substrate surface with a density of 0.02 to 0.3 molecular chain per square nanometer. Using the provided temperature-responsive cell culture substrate, cells obtained from various tissues can be efficiently cultured. This culturing method makes it possible to efficiently peel off a cell sheet by just changing the temperature, without causing damage.

Abstract: Tissue engineering methods and biochamber apparatus are provided for making tissue grafts for implantation into a patient. The methods include applying a sustained low magnitude pressure gradient transmurally across a permeable scaffold material using a media containing cells, preferably microvascular epithelial cells, to be deposited on the scaffold for the production of tissue grafts, preferably vascular grafts, to promote accelerated adhesion and maturation of cells on the scaffold material. Biochambers for preparing tubular tissue grafts are provided which contain connectors for holding a graft substrate, proximal and distal tubing for connection to an optional perfusion system, and structure for switching between transmural flow of a cell suspension across the graft substrate and translumenal flow through the lumen of the graft.

Abstract: A method of using a fluorinated polymer having a glass transition temperature below 40 C as a contrast agent in 19F magnetic resonance imaging (MRI) of a solid object, said solid object comprising said contrast agent. The invention relates to a solid object comprising a structural component and an imaging component, wherein the imaging component is at least one fluorinated polymer. The invention relates to a method for 19F MRI in solid state using a contrast agent comprising a fluorinated polymer as well as a method for in vivo visualizing a scaffold. It further relates to a method for in vivo monitoring the degradation of a solid object in time, wherein the degradation is monitored in time by using 19F MRI to visualize the solid object, and wherein the amount of degradation of the solid object is determined based on the decrease in the visibility of the amount of 19F.

Abstract: The present invention provides a method for arranging various cells as cell clusters in an arbitrary three-dimensional space and producing a three dimensional structure of a desired shape constituted exclusively by cells. Furthermore, the present invention provides a support provided with a substrate and a thread or needle-shaped material that penetrates the substrate and cell clusters for positioning cell clusters in arbitrary space. The support is provided with a sheet that can be removed as necessary for covering the substrate. Further, a method for using the support structure to position cell clusters in an arbitrary space and a method for the production of three-dimensional cell structures are provided.

Abstract: Methods of making cell sheets, tissue sheets and tissue-engineered blood vessels are provided. The methods include culturing cells on a nanoimprinted coated scaffold under hypoxic conditions to form an aligned cell sheet and then removing the aligned cell sheet from the scaffold. The cell sheets, tissue sheets and tissue-engineered blood vessels made the methods are also disclosed. The cell sheets, tissue sheets and tissue-engineered blood vessels may be implanted in subjects to treat a variety of conditions.

Abstract: The present invention provides methods and devices for the fabrication of 3D polymeric fibers having micron, sub-micron, and nanometer dimensions, as well as methods of use of these polymeric fibers.

Abstract: The invention discloses a porous composite biomaterial comprising of poly(?-glutamic acid)-g-chondroitin sulfate (?-PGA-g-CS) copolymer and poly(?-caprolactone). The composite biomaterial provides a three-dimensional microenviroment for using as a scaffold for tissue engineering and for supporting the attachment and proliferation of cells. The invention also discloses a method of producing a porous composite biomaterial.

Abstract: Equipment for treating wastewater by anaerobic ammonium oxidation includes an anaerobic ammonium oxidation vessel to receive water to be treated containing ammonium and nitrite and to denitrify ammonium and nitrite in the water by anaerobic ammonium oxidizing bacteria, forming denitrified treated water, an acclimatization vessel downstream from the anaerobic ammonium oxidation vessel to receive the denitrified treated water from the anaerobic ammonium oxidation vessel, the acclimization vessel containing an immobilizing material that collects the anaerobic ammonium oxidizing bacteria in the denitrified treated water as immobilized microorganisms attached to the immobilizing material, wherein the acclimatization vessel has a structure such that the immobilizing material is prevented from flowing out of the acclimatization vessel, and a pipe connecting the acclimatization vessel to the anaerobic ammonium oxidation vessel.

Abstract: A tissue engineering scaffold for cell, tissue or organ growth comprises a biocompatible porous polyurethane cellular material comprising a plurality of substantially spherical voids of diameter from 20 to 300 microns, preferably 80 to 200 microns, interconnected by generally elliptically shaped pores. The cellular material has a void content of from 85% to 98% and a surface area to volume of from 5 to 400 mm2/mm3, ideally from 20 to 80 mm2/mm3.

Abstract: The invention provides a substrate suitable for cell culture observation and a method of observation using the same. Crystalline carbon such as a graphite powder is mixed into a thermosetting resin such as a furan resin, and the mixture is molded in the shape of a sheet and carbonized to produce a carbon substrate; then, a cell is made to adhere to the carbon substrate, and the cell is caused to proliferate on the carbon substrate and observed using a microscope.

Abstract: Various methods for altering surface characteristics of a microsphere are provided. One method includes coupling an enolic acid to the microsphere to modify the surface characteristics of the microsphere. The surface characteristics may include charge density and/or pKa. A reagent can be coupled to the microsphere via the enolic acid. The reagent may include a biomolecule. The modified surface characteristics may increase a stability of the reagent when the reagent is coupled to the microsphere. The modified surface characteristics may also improve performance of an assay carried out with the microsphere. Another embodiment relates to a microsphere that includes an enolic acid coupled to a polymer core of the microsphere such that the enolic acid modifies surface characteristics of the microsphere. A reagent can be coupled to the microsphere via the enolic acid.

Abstract: A carrier for cell culture is provided which improves the cell proliferativity in serum-free culture and which is free from risk from infection factor contamination. The gist of the features of the present invention is to be formed of a crosslinked poly(meth)acrylic acid (salt) particle (A) and an artificial polypeptide (P) having at least one cell-adhesive minimal amino acid sequence (X) in one molecule and to have a water retention value of from 2 to 50 g/g. The (A) is preferably a particle produced by reversed phase suspension polymerization of an aqueous monomer solution containing (meth)acrylic acid and/or an alkali metal salt of (meth)acrylic acid. The (P) preferably has at least one auxiliary amino acid sequence (Y) in one molecule of the (P). The (X) is preferably an Arg Gly Asp sequence.

Abstract: Scaffolds for tissue engineering prepared from biocompatible, biodegradable polymer-based, lighter than or light as water microcarriers and designed for cell culturing in vitro in a rotating bioreactor are provided. Methods for preparation and use of these scaffolds as tissue engineering devices are also provided.

Abstract: The invention relates to a bioactive hydrogel as a hybrid material of heparin and star-branched polyethylene glycol with functionalized end groups, wherein the heparin is bound directly by reaction of the carboxyl groups activated with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimides/N-hydroxysulfosuccinimide (EDC/s-NHS) with the terminal amino groups of the polyethylene glycol covalently by amide bonds.

Abstract: A cell culture article including a pre-blocked, peptide-modified, polymer surface of the formula (I), where AAj represents at least one covalently bonded peptide, j is an integer of from 5 to 50, m, n, o, Sur, X, R, R?, and the mer ratio (m-o:n:o), including salts thereof, are as defined herein. Methods for making and using the cell culture article, as defined herein, are also disclosed.

Abstract: Surfaces of thermoplastic articles are rendered microporous by contacting the surface with a composition that includes a solvent. The article has a birefringence of 0.0001 or greater and the composition has a solvent strength configured to swell but not dissolve the polymer.

Abstract: A cell culture article including a microcarrier having a peptide-modified polymer surface of the formula (I) where AAj represents at least one covalently bonded peptide, j is an integer of from 5 to 50, m, n, o, Sur, X, R, R?, and the mer ratio (m-o:n:o), including salts thereof, are as defined herein. Also disclosed are methods for making and using the cell culture article, as defined herein.