Abstract: Compositions for forming a self-reinforcing composite biomatrix, methods of manufacture and use therefore are herein disclosed. Kits including delivery devices suitable for delivering the compositions are also disclosed. In some embodiments, the composition can include at least three components. In one embodiment, a first component can include a first functionalized polymer, a second component can include a second functionalized polymer and a third component can include silk protein or constituents thereof. In some embodiments, the composition can include at least one cell type and/or at least one growth factor. In some embodiments, the composition can include a biologic encapsulated, suspended, disposed within or loaded into a biodegradable carrier. In some embodiments, the composition(s) of the present invention can be delivered by a dual lumen injection device to a treatment area in situ, in vivo, as well as ex vivo applications.

Abstract: Polyhydroxyalkanoates (PHAs) from which pyrogen has been removed are provided. PHAs which have been chemically modified to enhance physical and/or chemical properties, for targeting or to modify biodegradability or clearance by the reticuloendothelial system (RES), are described. Methods for depyrogenating PHA polymers prepared by bacterial fermentation processes are also provided, wherein pyrogens are removed from the polymers without adversely impacting the polymers' inherent chemical structures and physical properties. PHAs with advantageous processing characteristics, including low melting points and/or solubility in non-toxic solvents, are also described. The PHAs are suitable for use in in vivo applications such as in tissue coatings, stents, sutures, tubing, bone, other prostheses, bone or tissue cements, tissue regeneration devices, wound dressings, drug delivery, and for diagnostic and prophylactic uses.

Abstract: An osteochondral plug includes a first scaffold and a second scaffold. The first scaffold may be a solid scaffold containing one or more pendant reactive functional groups. The second scaffold capable of reacting with the one or more pendant reactive functional groups of the first scaffold.

Abstract: This invention relates to a composite material that comprises a support member that has a plurality of pores extending through the support member and, located in the pores of the support member, and filling the pores of the support member, a macroporous cross-linked gel. The invention also relates to a process for preparing the composite material described above, and to its use. The composite material is suitable, for example, for separation of substances, for example by filtration or adsorption, including chromatography, for use as a support in synthesis or for use as a support for cell growth.

Abstract: A method for in situ formation of a medical device on biological tissue includes attaching a plurality of reactive members of a primary specific binding pair to a surface of the biological tissue, and providing a plurality of fibers having attached thereto a plurality of complementary reactive members of the primary specific binding pair, wherein upon contact of the reactive members on the surface of the biological tissue with the complimentary reactive members on the fibers, covalent bonds are formed between the reactive members and the complementary reactive members, thus adhering the fibers to the tissue. The fibers can incorporate functionalities which may cause them to bind to one another.

Abstract: The invention provides derivatives of IL-21 or variants thereof, methods of producing such variants, new variants of IL-21, and various methods of using such molecules.

Abstract: This invention relates to a composite material that comprises a support member that has a plurality of pores extending through the support member and, located in the pores of the support member, and filling the pores of the support member, a macroporous cross-linked gel. The invention also relates to a process for preparing the composite material described above, and to its use. The composite material is suitable, for example, for separation of substances, for example by filtration or adsorption, including chromatography, for use as a support in synthesis or for use as a support for cell growth.

Abstract: The present invention provides highly impact-resistant, water-soluble or water dispersible, low-dust granules comprising an active ingredient and methods for obtaining the same.

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: By detecting an antibody which immunologically reacts with amylase ?2-A in a sample, AIP or FT1DM is examined or the possibility of developing FT1DM is determined. For instance, detection of this antibody is carried out by an immunological method using an antigen which immunologically reacts with this antibody. The antigen is preferably a partial fragment containing the amino acid sequence of amino acid numbers 299 to 511 of human amylase ?2-A (SEQ ID NO: 1).

Abstract: This invention relates to a composite material that comprises a support member that has a plurality of pores extending through the support member and, located in the pores of the support member, and filling the pores of the support member, a macroporous cross-linked gel. The invention also relates to a process for preparing the composite material described above, and to its use. The composite material is suitable, for example, for separation of substances, for example by filtration or adsorption, including chromatography, for use as a support in synthesis or for use as a support for cell growth.

Abstract: This invention relates to a composite material that comprises a support member that has a plurality of pores extending through the support member and, located in the pores of the support member, and filling the pores of the support member, a macroporous cross-linked gel. The invention also relates to a process for preparing the composite material described above, and to its use. The composite material is suitable, for example, for separation of substances, for example by filtration or adsorption, including chromatography, for use as a support in synthesis or for use as a support for cell growth.

Abstract: This invention relates to a composite material that comprises a support member that has a plurality of pores extending through the support member and, located in the pores of the support member, and filling the pores of the support member, a macroporous cross-linked gel. The invention also relates to a process for preparing the composite material described above, and to its use. The composite material is suitable, for example, for separation of substances, for example by filtration or adsorption, including chromatography, for use as a support in synthesis or for use as a support for cell growth.

Abstract: This invention relates to a composite material that comprises a support member that has a plurality of pores extending through the support member and, located in the pores of the support member, and filling the pores of the support member, a macroporous cross-linked gel. The invention also relates to a process for preparing the composite material described above, and to its use. The composite material is suitable, for example, for separation of substances, for example by filtration or adsorption, including chromatography, for use as a support in synthesis or for use as a support for cell growth.

Abstract: Compositions for forming a self-reinforcing composite biomatrix, methods of manufacture and use therefore are herein disclosed. Kits including delivery devices suitable for delivering the compositions are also disclosed. In some embodiments, the composition can include at least three components. In one embodiment, a first component can include a first functionalized polymer, a second component can include a second functionalized polymer and a third component can include silk protein or constituents thereof. In some embodiments, the composition can include at least one cell type and/or at least one growth factor. In some embodiments, the composition can include a biologic encapsulated, suspended, disposed within or loaded into a biodegradable carrier. In some embodiments, the composition(s) of the present invention can be delivered by a dual lumen injection device to a treatment area in situ, in vivo, as well as ex vivo applications.

Abstract: This invention relates to a composite material that comprises a support member that has a plurality of pores extending through the support member and, located in the pores of the support member, and filling the pores of the support member, a macroporous cross-linked gel. The invention also relates to a process for preparing the composite material described above, and to its use. The composite material is suitable, for example, for separation of substances, for example by filtration or adsorption, including chromatography, for use as a support in synthesis or for use as a support for cell growth.

Abstract: A surface coating comprises a primer coat that permits adhesion of eukaryotic cells thereto, and a plurality of macromolecular structures attached to the primer coat. At least some of the macromolecular structures have a cell-resistant character, meaning that cells generally will not adhere to them. The macromolecular structures are distributed across an area of the primer coat so that the surface coating permits adhesion of the eukaryotic cells to the primer layer and resists the adhesion of non-eukaryotic cells. Typically, the primer coat comprises a self-assembled polymeric monolayer and the macromolecular structures comprise nanoscale hydrogels. Such surface coatings may be formed on articles of manufacture for insertion into the body, such as orthopedic devices.

Abstract: Compositions and methods useful in restorative dentistry are disclosed. Compositions of the present invention include a peptide, and a polymer matrix. The peptide is one capable of reacting with a source of mineralizing ions to initiate deposition of hydroxyapatite crystals within the polymer matrix. Compositions of the present invention are uniquely capable of sealing a junction between a dental restorative material and adjacent native tooth tissue.

Abstract: Disclosed are hydrogels wherein a polymer matrix is modified to contain a bifunctional poly(alkylene glycol) molecule covalently bonded to the polymer matrix. The hydrogels can be cross-linked using, for example, glutaraldehyde. The hydrogels may also be crosslinked via an interpenetrating network of a photopolymerizable acrylates. The hydrogels may also be modified to have pharmacologically-active agents covalently bonded to the poly(alkylene glycol) molecules or entrained within the hydrogel. Living cells may also be entrained within the hydrogels.

Abstract: A magnetic particle and fabrication method thereof. The magnetic particle comprises a polymer core, a magnetic material layer covering the polymer core, and a silicon containing layer covering the magnetic material layer. In addition, the magnetic particle may further comprise a coupling agent on the silicon containing layer, and an active molecule connected to the coupling agent. The magnetic particles provide controllable size, uniform diameter distribution, high magnetization, improved storage stability, and modified surface for targeting biomolecules for biomaterial separation and environmental analysis.

Abstract: Segmented water soluble polymers, containing a higher molecular weight segment linked to a lower molecular weight segment, are described. In one embodiment, the polymer segments are poly(ethylene glycol) segments. The segmented polymers are functionalized and are useful for conjugation to various moieties such as pharmacologically active substances. Also described are conjugates of such polymers and methods of their preparation.

Abstract: A porous solid ion exchange wafer having a combination of a biomolecule capture-resin and an ion-exchange resin forming a charged capture resin within said wafer. Also disclosed is a porous solid ion exchange wafer having a combination of a biomolecule capture-resin and an ion-exchange resin forming a charged capture resin within said wafer containing a biomolecule with a tag. A separate bioreactor is also disclosed incorporating the wafer described above.

Abstract: A support carrying an immobilized selective binding substance, that the support surface has a polymer containing the structural unit represented by the following General Formula (1) in an amount of 10% or more with respect all monomer units, and a selective binding substance is immobilized on the support surface by binding to the carboxyl group formed thereon via a covalent bond: (in General Formula (1), R1, R2, and R3 each represent an alkyl or aryl group or a hydrogen atom.

Abstract: A degradable hydrogel and a method of making a degradable hydrogel is disclosed herein. The method comprises obtaining a hydrophilic polymer having at least two hydroxyl groups, reacting the hydrophilic polymer with a di-functional monomer comprised of an acid halide group and an alkyl halide group to form an intermediate having an ester bond and a terminal alkyl halide group, reacting the terminal alkyl halide group of the intermediate with a metallic salt of a vinyl acid monomer to form a macromonomer comprised of an ester, an alkyl group spacer, and a terminal vinyl group, and polymerizing the macromonomer to form a degradable hydrogel. A method is also disclosed for varying the degradation rate of the hydrogel as a function of the chemical composition of the alkyl group spacer in the terminal linkage of the macromonomer.

Abstract: This invention is drawn to methods of using peptide-based antagonists of TGF-beta to facilitate the healing of cutaneous wounds that includes burns, lacerations and scrapes. The administration of peptide TGF-beta antagonists to wounds results in reduced scarring, wound contraction and deposition of extracellular matrix components, and increased rates of re-epithelialization during wound healing.

Abstract: The present invention provides a new and improved method for quantitative determination and/or identification of proteins in a sample. In one aspect, the invention provides a mass spectroscopic method for comparing protein levels in two or more samples by differentially isotopically labeling each sample's proteins' N- or C-termini. In another aspect, the invention provides a mass-spectroscopic method for identifying a sample as source for a protein from a mixture of two or more samples by differentially isotopically labeling each sample's proteins' N- or C-termini.

Abstract: Disclosed are hydrogels wherein a polymer matrix is modified to contain a bifunctional poly(alkylene glycol) molecule covalently bonded to the polymer matrix. The hydrogels can be cross-linked using, for example, glutaraldehyde. The hydrogels may also be crosslinked via an interpenetrating network of a photopolymerizable acrylates. The hydrogels may also be modified to have pharmacologically-active agents covalently bonded to the poly(alkylene glycol) molecules or entrained within the hydrogel. Living cells may also be entrained within the hydrogels.

Abstract: The present invention includes a bifunctional specificity structure that includes a peptide linker having a first and a second binding domain, wherein the first binding domain is selective for a first biomaterial and the second binding domain is selective for a second biomaterial. The present invention also includes a method of making and identifying the bifunctional structure of the present invention and methods of using the same.

Abstract: The subject invention concerns a composite comprising an organic fluid-swellable, fibrous matrix, such as collagen, and a mineral phase, such as calcium carbonate or phosphate mineral phase, for use as a biomimetic of bone. In another aspect, the subject invention concerns a process for making a composite involving the inclusion of acidic polymers to a supersaturated mineralizing solution, in order to induce an amorphous liquid-phase precursor to the inorganic mineral, which is then absorbed (pulled by capillary action) into the organic matrix. Advantageously, once solidified, a high mineral content can be achieved, with the inorganic mineral crystals embedded within the collagen fibers (intrafibrillarly) and oriented such that they are aligned along the long axes of the fibers of the organic matrix, thereby closely mimicking the natural structure of bone.

Abstract: The invention provides compositions for intracellular delivery of biotinylated cargo. The compositions comprise a complex formed between (a) a fusion protein comprising a protein transduction domain linked to streptavidin and (b) a biotinylated cargo for intracellular delivery. In some embodiments, the protein transduction domain comprises the protein transduction domain of the Human Immunodeficiency Virus type 1 (HIV-1) TAT protein. The complex may further comprise a biotinylated endosomal releasing polymer, such as a poly(propylacrylic acid) polymer. The invention also provides methods for obtaining intracellular delivery of biotinylated cargo and methods for obtaining cytoplasmic delivery of biotinylated cargo.

Abstract: The subject invention concerns a composite comprising an organic fluid-swellable matrix, such as collagen, and mineral phase, such as calcium carbonate or phosphate mineral phase, for use as a biomimetic of bone. In another aspect, the subject invention concerns a process for making a composite involving the inclusion of acidic polymers to a supersaturated mineralizing solution, in order to induce an amorphous liquid-phase precursor to the inorganic mineral, which is then absorbed (pulled by capillary action) into the interstices of the organic matrix, and subsequently mineralizes via solidification and crystallization of the precursor phase. The present invention further concerns a method of treating a patient suffering from a bone defect by applying a biomimetic composite to the bone defect site.

Abstract: The subject invention concerns a composite comprising an organic fluid-swellable, fibrous matrix, such as collagen, and a mineral phase, such as calcium carbonate or phosphate mineral phase, for use as a biomimetic of bone. In another aspect, the subject invention concerns a process for making a composite involving the inclusion of acidic polymers to a supersaturated mineralizing solution, in order to induce an amorphous liquid-phase precursor to the inorganic mineral, which is then absorbed (pulled by capillary action) into the organic matrix. Advantageously, once solidified, a high mineral content can be achieved, with the inorganic mineral crystals embedded within the collagen fibers (intrafibrillarly) and oriented such that they are aligned along the long axes of the fibers of the organic matrix, thereby closely mimicking the natural structure of bone.

Abstract: A deformable stamp for patterning a surface. The stamp can be placed in contact with an entire 3-dimensional object, such as a rod, in a single step. The stamp can also be used to pattern the inside of a tube or rolled over a surface to form a continuous pattern. The stamp may also be used for fluidic patterning by flowing material through channels defined by raised and recessed portions in the surface of the stamp as it contacts the substrate. The stamp may be used to deposit self-assembled monolayers, biological materials, metals, polymers, ceramics, or a variety of other materials. The patterned substrates may be used in a variety of engineering and medical applications.

Abstract: This invention relates to agents which bind to cell surface receptors; methods to manufacture said agents; therapeutic compositions comprising said agents; and screening methods to identify novel agents.

Abstract: The present invention provides a new and improved method for reducing the complexity of a proteomic sample, and preferably also for allowing identification of proteins in the sample. In one aspect, the invention provides a highly efficient method for identifying proteins in a proteomic sample by characterizing a single N-terminal peptide per protein. In another aspect, the invention provides a method for identifying proteins in a proteomic sample by characterizing a single C-terminal peptide per protein. In another aspect, the present invention provides a method for quantitative determination of differential protein expression and/or modification in different samples. In another aspect, the invention relates to kits useful for conveniently performing a method in accordance with the invention.

Abstract: This invention provides novel methods and reagents for specifically delivering biologically active compounds to phagocytic mammalian cells. The invention also relates to specific uptake of such biologically active compounds by phagocytic cells and delivery of such compounds to specific sites intracellularly. The invention specifically relates to methods of facilitating the entry of antiviral and antimicrobial drugs and other agents into phagocytic cells and for targeting such compounds to specific organelles within the cell. The invention specifically provides compositions of matter and pharmaceutical embodiments of such compositions comprising conjugates of such antimicrobial drugs and agents covalently linked to particulate carriers generally termed microparticles. In particular embodiments, the antimicrobial drug is covalently linked to a microparticle via a cleavable linker moiety that is non-specifically cleaved in a phagocytic cell.

Abstract: Multi-armed, monofunctional, and hydrolytically stable polymers are described having the structure wherein Z is a moiety that can be activated for attachment to biologically active molecules such as proteins and wherein P and Q represent linkage fragments that join polymer arms polya and polyb, respectively, to central carbon atom, C, by hydrolytically stable linkages in the absence of aromatic rings in the linkage fragments. R typically is hydrogen or methyl, but can be a linkage fragment that includes another polymer arm. A specific example is an mPEG disubstituted lysine having the structure where mPEGa and mPEGb have the structure CH3O—(CH2CH2O)nCH2CH2— wherein n may be the same or different for polya- and polyb- and can be from 1 to about 1,150 to provide molecular weights of from about 100 to 100,000.

Abstract: The present invention relates to magnetic fine particles having immobilized thereto a polymer having an upper critical solution temperature, and a process for producing the same, a method of separating or concentrating a microorganism, a method of purifying, detecting, or concentrating a nucleic acid, a separating agent, a method of separating a biological substance, and a method of converting a substance.

Abstract: The invention relates to a macroporous plastics bead material with an average particle diameter from 10 to 1000 ?m, containing a copolymer of a) 5-60 wt. % vinylically polymerizable monomers with a water solubility of at least 1% at 20° C., b) 1-40 wt. % vinylically polymerizable monomers with an additional functional group, which can enter into covalent bonds with the nucleophilic groups of the ligands in a polymer-like reaction, c) 10-40 wt. % hydrophilic, crosslinking radical-polymerizable monomers with two or more ethylenically unsaturated polymerizable groups and d) 10-60 wt. % vinylically polymerizable monomers with a water solubility of at most 1% at 20° C. are contained, as a rule with the monomers a) to d) adding up to 100%.

Abstract: Methods and apparatus for bone implants that allow for the directed application of an osteogenic compound. The implant is preferably constructed of a biodegradable polymer formed into a structure having micro-architectural features and includes features that allow for in-situ application of a liquid biodegradable polymer to securely attach the implant to the surrounding tissue. The implant is constructed with a nozzle connected to a fluid supply that can be injected through a central channel and one or more distribution channels. The implant is designed so as to provide structural support to the damaged area. The implant and the fluid supply are preferably biodegradable polymers that contain an osteogenic material.

Abstract: This invention relates to methods for the stabilization, storage and delivery of biologically active macromolecules, such as proteins, peptides and nucleic acids. In particular, this invention relates to protein or nucleic acid crystals, formulations and compositions comprising them. Methods are provided for the crystallization of proteins and nucleic acids and for the preparation of stabilized protein or nucleic acid crystals for use in dry or slurry formulations. The present invention is further directed to encapsulating proteins, glycoproteins, enzymes, antibodies, hormones and peptide crystals or crystal formulations into compositions for biological delivery to humans and animals. According to this invention, protein crystals or crystal formulations are encapsulated within a matrix comprising a polymeric carrier to form a composition.

Abstract: This invention relates to a composite material that comprises a support member that has a plurality of pores extending through the support member and, located in the pores of the support member, and filling the pores of the support member, a macroporous cross-linked gel. The invention also relates to a process for preparing the composite material described above, and to its use. The composite material is suitable, for example, for separation of substances, for example by filtration or adsorption, including chromatography, for use as a support in synthesis or for use as a support for cell growth.

Abstract: A porous solid ion exchange wafer having a combination of a biomolecule capture-resin and an ion-exchange resin forming a charged capture resin within said wafer. Also disclosed is a porous solid ion exchange wafer having a combination of a biomolecule capture-resin and an ion-exchange resin forming a charged capture resin within said wafer containing a biomolecule with a tag. A separate bioreactor is also disclosed incorporating the wafer described above.

Abstract: A method of patterning materials, such as proteins, on a contoured surface by depositing them onto protrusions on a surface, and a cell containment device that may be constructed by this method, are provided. The method may involve selectively depositing a material on a substrate including a contoured surface including protrusions and recesses. By applying a first fluid to the contoured surface and allowing the first fluid to distribute across only a portion of the contoured surface, a material may be deposited on the protrusions and not the recesses, or on the recesses and not the protrusions. Such a method may be used to selectively pattern cells or other materials on substrates.

Abstract: The present invention describes improved microfluidic systems and procedures for fabricating improved microfluidic systems, which contain one or more levels of microfluidic channels. The methods for fabrication the systems disclosed can provide a convenient route to topologically complex and improved microfluidic systems. The microfluidic systems can include three-dimensionally arrayed networks of fluid flow paths therein including channels that cross over or under other channels of the network without physical intersection at the points of cross over. The microfluidic networks can be fabricated via replica molding processes utilizing mold masters including surfaces having topological features formed by photolithography. The present invention also involves microfluidic systems and methods for fabricating complex patterns of materials, such as biological materials and cells, on surfaces utilizing the microfluidic systems.

Abstract: A biocompatible material genus serves as the foundation for multiple material composition species, each adapted to a specific therapeutic indication.

Abstract: Nanopatterned devices are easily fabricated, over large surface areas when desired, by forming a multilayer article of deformable substrate, brittle layer, and coating layer, and deforming the multilayer film such that a plurality of cracks are formed therein. The cracks have different physicochemical properties than the non-cracked coating layer, and advantageously serve as attachment points for culturing microorganisms.

Abstract: Arrays including microparticles having probe and marker moieties are used for the detection of a target in a sample. Microparticles are randomly immobilized on at least a portion of a substrate. A detection scheme is performed to detect the marker associated with the microparticle and the identity of the probe, and any target bound to the probe.

Abstract: The invention relates to a stimulus-responding polymer obtained by polymerizing at least a monomer represented by a general formula (1) and a monomer represented by a general formula (2), and a separation method or concentration method of microorganisms, a purification method, detection method or concentration method of nucleic acids, a separating agent, a separation method of biomaterials and a conversion method of materials, which use this polymer, (in the formula, R11 represents hydrogen atom or methyl group, and R12 represents single bond or a straight or branched alkylene group having from 1 to 5 carbon atoms) (in the formula, R13 represents hydrogen atom or methyl group, and R14 represents hydrogen atom, a straight, branched or cyclic alkyl group, alkoxyl group or alkylamino group having from 1 to 10 carbon atoms, an aryl group or a heterocyclic group).

Abstract: A substrate comprises a surface, and a plurality of moieties, on at least a portion of the surface. The moieties are moieties of formula: Surf-L—Q—T, where —T comprises a reactant ligand, and Surf- designates where the moiety attaches to the surface. The substrate can be made into a protein chip by the reaction of a reactant ligand and a fusion polypeptide, where the fusion polypeptide includes a capture polypeptide moiety which corresponds to the reactant ligand.