Support Is A Resin Patents (Class 435/396)
  • Patent number: 7195913
    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.
    Type: Grant
    Filed: October 5, 2001
    Date of Patent: March 27, 2007
    Assignee: SurModics, Inc.
    Inventors: Patrick E. Guire, Kristin S. Taton, John V. Wall
  • Patent number: 7022522
    Abstract: A polymer scaffold is provided comprising an extensively interconnected macroporous network. The polymer scaffold embodies macropores having a diameter in a range of 0.5-3.5 mm, and preferably in a range of about 1.0-2.0 mm. The polymer scaffold is prepared using a novel process which advantageously combines the techniques of particulate leaching and phase inversion to render a process that provides amplified means by which to control the morphology of the resulting polymer scaffold. The polymer scaffold has utility in the area of tissue engineering, particularly as a scaffold for both in vitro and in vivo cell growth. The polymer scaffold may be produced using pure polymer or alternatively a composite material may be formed consisting of a macroporous polymer scaffold and osteoclast-resorbable calcium phosphate particles with a binding agent binding the calcium phosphate particles to the polymer scaffold.
    Type: Grant
    Filed: April 30, 2002
    Date of Patent: April 4, 2006
    Inventors: Limin Guan, Chantal E. Holy, Molly S. Shoichet, John E. Davies
  • Patent number: 6875442
    Abstract: A polymer scaffold is provided comprising an extensively interconnected macroporous network. The polymer scaffold embodies macropores having a diameter in a range of 0.5-3.5 mm, and preferably in a range of about 1.0-2.0 mm. The polymer scaffold is prepared using a novel process which advantageously combines the techniques of particulate leaching and phase inversion to render a process that provides amplified means by which to control the morphology of the resulting polymer scaffold. The polymer scaffold has utility in the area of tissue engineering, particularly as a scaffold for both in vitro and in vivo cell growth.
    Type: Grant
    Filed: August 13, 2002
    Date of Patent: April 5, 2005
    Assignee: Bonetec Corporation
    Inventors: Chantal E. Holy, Molly S. Shoichet, John E. Davies
  • Patent number: 6858146
    Abstract: Artificial liver devices and methods for using the devices to purify a biological fluid are disclosed. The methods include the use of living hepatocytes (23) which are either unattached or attached to inert carriers and suspended in a cell culture medium which circulates in the devices with the hepatocytes (23). Blood or plasma passes on one side (7?) of semi-permeable membranes, on the other side (7) of which is the cell culture medium and across which is a concentration and/or pressure gradient. Solutes diffusing across the membrane into the cell culture medium are metabolized by the hepatocytes (23) and/or captured by additional removal means (4). Those undesirable substances which do not diffuse out of the blood or plasma into the hepatocyte containing culture medium are captured by additional removal means (50).
    Type: Grant
    Filed: September 27, 1994
    Date of Patent: February 22, 2005
    Assignee: Xenogenics
    Inventors: Edward F. Myers, Albert P. Li, Achilles A. Demetriou
  • Publication number: 20040203146
    Abstract: A composite scaffold for engineering a heterogeneous tissue is provided. The composite scaffold includes: (a) a first scaffold being capable of supporting, formation of a first tissue type thereupon; and (b) a second scaffold being capable of supporting formation of a second tissue type thereupon; wherein the first scaffold and the second scaffold are arranged with respect to each other such that when the first scaffold supports the first tissue type and the second scaffold supports the second tissue type, a distance between any cell of the second tissue type and the first tissue type does not exceed 200 $G(m)m.
    Type: Application
    Filed: May 25, 2004
    Publication date: October 14, 2004
    Inventors: Dan Gazit, Avraham Domb, Gudi Turgeman
  • Patent number: 6743630
    Abstract: A method of preparing a protein array based on biochemical protein-protein interaction is provided. An array of a first protein which includes a PDZ domain is deposited on a substrate. A second protein, which includes an amino acid sequence (S/T)—X—(V/I/L)—COOH (each hyphen represents a peptide bond, each parenthesis encloses amino acids which are alternatives to one other, each slash within such parentheses separates the alternative amino acids, and the X represents any amino acid which is selected from the group comprising the twenty naturally occurring amino acids), is applied to the first protein array. The amino acid sequence (S/T)—X—(V/I/L)—COOH of the second protein is bound to the PDZ domain of the first protein.
    Type: Grant
    Filed: March 6, 2002
    Date of Patent: June 1, 2004
    Assignee: The Trustees of Columbia University in the City of New York
    Inventor: Taka-Aki Sato
  • Patent number: 6730298
    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.
    Type: Grant
    Filed: January 20, 1998
    Date of Patent: May 4, 2004
    Assignees: Massachusetts Institute of Technology, Children's Medical Center Corporation
    Inventors: Linda Griffith-Cima, Anthony Atala, Charles A. Vacanti, Keith T. Paige
  • Patent number: 6699665
    Abstract: A multiple level micro-array system for integrating micro-arrays of biomolecules, including biological, chemical and biochemical elements. The multiple level micro-arrays are formed using soft lithography techniques and elastomeric membranes to shield or pattern various portions of a suitable substrate with biomolecules. Additional levels are formed using membranes with various through holes which either isolate, stratify or shield the patterned biomolecules from subsequent patterning or addition of an assay solution.
    Type: Grant
    Filed: November 8, 2000
    Date of Patent: March 2, 2004
    Assignee: Surface Logix, Inc.
    Inventors: Enoch Kim, David Duffy
  • Patent number: 6653089
    Abstract: The present invention is directed, in certain embodiments, to improved, small scale systems and methods able to selectively treat parts of a single cell, including, in certain embodiments, portions of a main body portion of a single cell, and able, in certain embodiments, to establish long-term gradients of active substances within subcellular regions of a single cell. The present invention provides, in some embodiments, techniques for selectively contacting a portion of the surface of a biological cell with a fluid or fluid component carrying a particular potential for a biophysical or biochemical interaction with the cell, and simultaneously contacting a different portion of the surface of the cell with another fluid or fluid component having a different potential for the biophysical or biochemical interaction with the cell.
    Type: Grant
    Filed: September 18, 2001
    Date of Patent: November 25, 2003
    Assignees: President and Fellows of Harvard College, Children's Medical Center Corporation
    Inventors: Shuichi Takayama, Emanuele Ostuni, Philip LeDuc, Keiji Naruse, Donald E. Ingber, George M. Whitesides
  • Patent number: 6627422
    Abstract: A device is provided containing cells or tissue distributed on a filamentous cell-supporting matrix which is encapsulated by a semi-permeable membrane which can be immunoisolatory. The matrix may be formed of a plurality of monofilaments twisted into yarn that is in non-woven strands, or of the monofilaments or yarn woven into a mesh. Configurations of the matrix include a hollow cylinder, tube, solid cylinder or cord. A coating of extracellular matrix molecules may be on the matrix, or the matrix may be treated with plasma irradiation to enhance cell adhesion. The device can be made by inserting the matrix in a hollow membrane tube, injecting cells or tissue into the tube and sealing ends of the tube. The device is particularly useful for implantation into a mammalian host to provide therapy resulting from a biologically active molecule produced by the cells and tissue.
    Type: Grant
    Filed: December 21, 2000
    Date of Patent: September 30, 2003
    Assignee: Neurotech S.A.
    Inventors: Rebecca Li, David Rhein
  • Publication number: 20030175410
    Abstract: Methods, compositions, and apparatus for preparing biomimetic scaffolds are provided. The methods, compositions, and apparatus are compatible with both in situ and external scaffold preparation. Also provided are methods for preparing scaffolds having 3-D spatial and/or temporal gradients of therapeutic compounds, such as, growth factors, antibiotics, immunosuppressants, analgesics, etc.
    Type: Application
    Filed: March 18, 2003
    Publication date: September 18, 2003
    Inventors: Phil G. Campbell, Lee E. Weiss
  • Publication number: 20030129751
    Abstract: The present invention relates to a method for producing a tissue-engineered organ or organ portion or specific section thereof comprising the steps of loading organoid units into a biocompatible polymer scaffold and implanting the polymer scaffold into a subject. Organs produced by this method are also encompassed by the invention. Organoid units can be derived from tissues including, but not limited to, spleen, lung, liver, kidney, pancreas, endocrine tissue, heart, esophagus, colon, stomach, gall bladder and uterus. The resulting engineered tissue can comprise spleen, lung, liver, kidney, pancreas, endocrine, cardiac muscle, esophagus, colon, stomach, gall bladder or uterus. The invention further relates to a tissue-engineered organ or organ portion or specific section thereof comprising compact tissue grown in a biocompatible polymer scaffold, wherein the tissue is derived from spleen, lung, liver, kidney, pancreas, endocrine, heart, esophagus, colon, stomach, gall bladder or uterus.
    Type: Application
    Filed: May 16, 2002
    Publication date: July 10, 2003
    Inventors: Tracy C. Grikscheit, Jennifer Ogilvie, Joseph P. Vacanti
  • Patent number: 6586246
    Abstract: Three-dimensional porous biodegradable and biocompatible, polymeric scaffolds for tissue engineering are prepared by a method involving effervescing of an effervescent salt in a gel to result in a porous structure. A polymer is dissolved in an organic solvent to prepare a polymer solution of high viscosity. Optionally, the polymer solution is mixed with an organic solvent that does not dissolve the polymer to concentrate the solution. An effervescent salt is homogeneously mixed with the polymer solution to give a polymer/salt/organic solvent mixed gel. The organic solvent is removed from the mixed gel to produce an organic solvent-free polymer/salt gel slurry. The gel slurry is submerged in a hot aqueous solution or acidic solution to cause the salt to effervesce at room temperature to form a porous three-dimensional polymeric structure. The polymeric structure is washed with distilled water and freeze-dried to yield a scaffold that is suitable for cell or tissue culture.
    Type: Grant
    Filed: February 6, 2001
    Date of Patent: July 1, 2003
    Assignee: Innotech Medical, Inc.
    Inventors: Jun-Jin Yoon, Tae-Gwan Park, Yoon-Sung Nam
  • Publication number: 20030109934
    Abstract: A method by which immune responses to cortical bone grafts and other substrates (e.g., cement, IPN, etc.) can be minimized and at the same time graft osteoinductive potential can be improved, and improved graft substrate materials are disclosed. The method of the invention provides new types of bone grafts that incorporate into host bone more thoroughly and more rapidly, eliminating long-term complications, such as fracture, non-union, infection, and rejection. In the method of the invention, bone grafts or other substrates are modified to have an osteoinductive surface modification that the recipient's body will accept as its own tissue type and therefore will not reject or otherwise cause to fail. The osteoinductive surface modification comprises a biopolymer matrix coating that is seeded with periosteal cells that have been previously harvested either from the graft recipient or from an allogenic or xenogenic donor source.
    Type: Application
    Filed: December 27, 2002
    Publication date: June 12, 2003
    Applicant: Cambridge Scientific, Inc.
    Inventors: Kai-Uwe Lewandrowski, Shrikar Bondre, Debra J. Trantolo, Maurice V. Cattaneo, Joseph D. Gresser, Donald L. Wise
  • Publication number: 20030050709
    Abstract: The present invention discloses an in vitro engineered osteochondral graft comprising a porous matrix block, more particularly, a porous polylactic acid polymer block, press-coated with mesenchymal stem cells (MSCs), wherein a cartilage layer is formed on the surface of the matrix block. This invention may be used for treating articular cartilage defects.
    Type: Application
    Filed: February 25, 2002
    Publication date: March 13, 2003
    Inventors: Ulrich Noth, Rocky S. Tuan
  • Publication number: 20030008395
    Abstract: A polymer scaffold is provided comprising an extensively interconnected macroporous network. The polymer scaffold embodies macropores having a diameter in a range of 0.5-3.5 mm, and preferably in a range of about 1.0-2.0 mm. The polymer scaffold is prepared using a novel process which advantageously combines the techniques of particulate leaching and phase inversion to render a process that provides amplified means by which to control the morphology of the resulting polymer scaffold. The polymer scaffold has utility in the area of tissue engineering, particularly as a scaffold for both in vitro and in vivo cell growth.
    Type: Application
    Filed: August 13, 2002
    Publication date: January 9, 2003
    Inventors: Chantal E. Holy, Molly S. Shoichet, John E. Davies
  • Patent number: 6472210
    Abstract: A polymer scaffold is provided having an extensively interconnected macroporous network with macropores having microporous struts as walls. Macropore diameter ranges from about 0.5 to about 3.5 mm. The polymer may be a biocompatible, biodegradable polymer such as poly(lactide-co-glycolide) containing 75% polylactide and 25% polyglycolide. The polymer scaffold is prepared by mixing a liquid polymer with particles, precipitating the liquid polymer with a non-solvent for the liquid polymer and dissolving the particles with a solvent to form the macroporous polymer scaffold which preferably has porosity greater than 50%. The surface of the polymer scaffold may be modified by acid or base treatment, or by collagen or calcium phosphate deposition. The polymer scaffold has utility for tissue engineering, particularly as a scaffold for in vitro and in vivo cell growth.
    Type: Grant
    Filed: May 26, 2000
    Date of Patent: October 29, 2002
    Assignee: Bonetec Corporation
    Inventors: Chantal E. Holy, Molly S. Shoichet, John E. Davies
  • Publication number: 20020133235
    Abstract: Cells grown on a microcarrier are separated from the microcarrier by enzymatically digesting the microcarrier. More specifically, chondrocytes may be grown on dextran microcarrier beadlets and then the beadlets digested using dextranase to separate the chondrocytes from the carrier. Cells can also be grown on chitosan microcarriers to be used for implantation. In addition, cells can be grown on polysaccharide polymers to be used as implant devices. Various polymers serve as scaffolds for cells to be used for implantation. The polymers can be used for cell culture as well as for preparing scaffolds useful for tissue replacement such as cartilage tissue.
    Type: Application
    Filed: February 4, 2002
    Publication date: September 19, 2002
    Inventors: David S. Hungerford, Carmelita G. Frondoza, Afshin Sohrobi, Alan H. Shikani, Abraham J. Domb
  • Patent number: 6417000
    Abstract: The invention relates to water-insoluble polymers which promote cell proliferation, contain carboxylate and sulfonate groups and are obtainable by free radical copolymerization of one or more aliphatically unsaturated monomers containing carboxylate groups, or the correspondingly functionalized derivatives of the monomers, as component I with one or more aliphatically unsaturated monomers containing sulfonate groups, or the correspondingly functionalized derivatives of the monomers, as component II and a component III which comprises an aliphatically unsaturated monomer or several aliphatically unsaturated monomers, the correspondingly functionalized derivatives being converted into carboxylate and sulfonate groups after the copolymerization, and to a process for their preparation, wherein the polymers are useful for forming articles which promote cell proliferation.
    Type: Grant
    Filed: November 15, 2001
    Date of Patent: July 9, 2002
    Assignee: Le Groupement d'Intérét Public Thérapeutiques Substitutives Institut Galilée, Université Paris-Nord
    Inventors: Frank Hill, by Friedrich Frank Hill, by Regina Luise Hill, Peter Ottersbach, Graciella Djavid, Marcel Jozefowicz, Veronique Migonney, Jean-Pierre Vairon
  • Publication number: 20020072798
    Abstract: Novel scaffolds for tissue engineering muscle are provided that include copolymers of a polyalkylene glycol and an aromatic polyester in the form of a matrix. The scaffold can include autologous muscle cells and/or stem cells.
    Type: Application
    Filed: September 19, 2001
    Publication date: June 13, 2002
    Inventors: Jens Uwe Riesle, Clemens Antoni van Blitterswijk, Maria Papadaki, Robert Langer
  • Patent number: 6399700
    Abstract: Synthetic comb copolymers which elicit controlled cellular response, methods of applying these polymers to various surfaces, and methods of using the polymers for modifying biomaterial surfaces, in tissue engineering applications and as drug delivery devices are provided. The comb copolymers are comprised of hydrophobic polymer backbones and hydrophilic, non-cell binding side chains which can be end-capped with cell-signaling ligands that guide cellular response. By mixing non-cell binding combs with ligand-bearing combs, the surface concentration and spatial distribution of one or more types of ligands, including adhesion peptides and growth factors, can be tuned on a surface to achieve desired cellular response. In one embodiment, the combs are used as stabilizing agents for dispersion polymerization of latexes. The comb-stabilized latexes can be applied to substrates by standard coating operations to create a bioregulating surface, or used as drug delivery agents.
    Type: Grant
    Filed: March 26, 2001
    Date of Patent: June 4, 2002
    Assignee: Massachusetts Institute of Technology
    Inventors: Anne M. Mayes, Linda G. Griffith, Darrell J. Irvine, Pallab Banerjee, Terry D. Johnson
  • Patent number: 6379962
    Abstract: A polymer scaffold is provided having an extensively interconnected macroporous network with macropores having microporous struts as walls. Macropore diameter ranges from about 0.5 to about 3.5 mm. The polymer may be a biocompatible, biodegradable polymer such as poly(lactide-co-glycolide) containing 75% polylactide and 25% polyglycolide. The polymer scaffold is prepared by mixing a liquid polymer with particles, precipitating the liquid polymer with a non-solvent for the liquid polymer and dissolving the particles with a solvent to form the macroporous polymer scaffold which preferably has porosity greater than 50%. The surface of the polymer scaffold may be modified by acid or base treatment, or by collagen or calcium phosphate deposition. The polymer scaffold has utility for tissue engineering, particularly as a scaffold for in vitro and in vivo cell growth.
    Type: Grant
    Filed: November 13, 1998
    Date of Patent: April 30, 2002
    Assignee: Bonetec Corporation
    Inventors: Chantal E. Holy, Molly S. Shoichet, John E. Davies
  • Patent number: 6365149
    Abstract: The present patent describes a three-dimensional interconnected open cell porous foams that have a gradient in composition and/or microstructure through one or more directions. These foams can be made from a blend of absorbable and biocompatible polymers that are formed into foams having a compositional gradient transitioning from predominately one polymeric material to predominately a second polymeric material. These gradient foams are particularly well suited to tissue engineering applications and can be designed to mimic tissue transition or interface zones.
    Type: Grant
    Filed: December 19, 2000
    Date of Patent: April 2, 2002
    Assignee: Ethicon, Inc.
    Inventors: Murty N. Vyakarnam, Mark C. Zimmerman, Angelo George Scopelianos, Mark B. Roller, David V. Gorky
  • Patent number: 6309635
    Abstract: A method is provided whereby cells having a desired function are seeded on and into biocompatible, biodegradable or non-degradable porous polymer scaffolding matrix, previously implanted in a patient and infiltrated with blood vessels and connective tissue, to produce a functional organ equivalent. The resulting organoid is a chimera formed of parenchymal elements of the donated tissue and vascular and matrix elements of the host. The matrix should be compression resistant and a non-toxic, porous template for vascular ingrowth. The pore size, usually between approximately 100 and 300 microns, should allow vascular and connective tissue ingrowth throughout approximately 10 to 90% of the matrix, and the injection of cells such as hepatocytes without damage to the cells or patient. The introduced cells attach to the connective tissue and are fed by the blood vessels.
    Type: Grant
    Filed: November 28, 1994
    Date of Patent: October 30, 2001
    Assignees: Children's Medical Center Corp., Massachusetts Institute of Technology
    Inventors: Donald E. Ingber, Robert S. Langer, Joseph P. Vacanti
  • Patent number: 6303375
    Abstract: A matrix for supporting cells such as animal cells is provided that enables cells to be supported at high efficiency and density in a short period. The matrix contains a plurality of cone shaped pores having an average diameter opening in an upstream surface of the matrix of from 500 to 1500 &mgr;m. The diameter decreases from the upstream surface to a downstream surface, and the average diameter of the cone shaped pores in the whole matrix is from 100 to 1000 &mgr;m. The matrix also contains a plurality of communicating pores that communicate with the cone shaped pores and with each other. These pores have an average diameter of from 5 to 100 &mgr;m, and the diameter decreases from a pore opening positioned near one surface of the matrix or near an interior surface of the cone shaped pores to a pore opening positioned remote from the surfaces. The matrix may also contain a plurality of column shaped pores having an average diameter of 100 to 1000 &mgr;m.
    Type: Grant
    Filed: June 23, 1999
    Date of Patent: October 16, 2001
    Assignee: Terumo Kabushiki Kaisha
    Inventors: Tetsuhiro Kimura, Norifumi Tokunaga, Yoshitaka Omura
  • Publication number: 20010024828
    Abstract: An object of this invention is to offer an incubation carrier for achieving high activity and high density of the microorganism in a bioreactor, in a treatment of waste water, etc.
    Type: Application
    Filed: May 9, 2001
    Publication date: September 27, 2001
    Inventor: Takaaki Maekawa
  • Patent number: 6245557
    Abstract: A cell culture assembly is provided. The assembly includes a housing having a first end and a second end and the side wall disposed between the first and second ends. The side wall and the second end define a cell growth chamber and the first end defines an opening for receiving media and starter culture. The assembly includes a continuous elongated ribbon having a leader at one end and a cell growth portion formed into turns and disposed within the chamber. The first end of the ribbon is threaded through an aperture in the side wall with the leader exposed on the outside of the housing. A sealing member is disposed over the leader and the aperture to hermetically seal the aperture. The sealing member is removable to access the leader to pull the ribbon through the aperture. In a preferred embodiment, a squeegee assembly is disposed adjacent the aperture and is configured to apply a squeegee action to the ribbon as the ribbon is pulled through the aperture.
    Type: Grant
    Filed: January 5, 2000
    Date of Patent: June 12, 2001
    Inventors: Robert P. Fouts, Anthony J. Gardner
  • Patent number: 6214593
    Abstract: A suspension of animal cells is incubated with supports to adhere the cells to the supports. Preferably, the supports have pores that provide pore volume, and the cells are grown during incubation until most of the available pore volume is filled with cells. An encapsulating layer is then formed around the supported cells by exposing the cells on the supports to a reactive gas composed of a carrier gas such as sterile air saturated with an inorganic alkoxide followed by treatment with steam to hydrolyze residual alkoxide groups. The encapsulated cells are stored by immersion in culture media. The cells may be in the form of cell aggregates, and the supports can be sterilized. The supports and encapsulating layer can have pores of a size that permit free exchange nutrients and metabolic products, and excludes the cells from contacting antibodies or immune cells when implanted. The encapsulated cells can used in an extracorporeal device or implanted directly.
    Type: Grant
    Filed: November 27, 1998
    Date of Patent: April 10, 2001
    Assignee: Biosil A.G.
    Inventors: Giovanni Carturan, Maurizio Muraca, Renzo Dal Monte
  • Patent number: 6214619
    Abstract: A bioreactor carrier is provided using an organic polymer substance having a water absorptivity of 50 to 1,700%, and containing an inorganic salt, organic nitrogen source and/or organic carbon source utilizable as a nutrient by animal cells, plant cells and/or microorganisms which fix to the carrier for uses such as substance production, harmful substance treatment, waste oil treatment, wastewater treatment and deodorization. A preferred polymer substance is a water swellable thermoplastic polyurethane gel having the water absorptivity and a swelling rate of volume of 150 to 4,000%. The polyurethane gel is obtained by reacting together a long-chain diol compound, a short-chain diol compound and a diisocyanate compound. The long-chain diol compound has a number-average molecular weight of 400 to 10,000, and is selected from an ethylene oxide-propylene oxide copolymer having an ethylene oxide content not less than 70% and a polyethylene glycol.
    Type: Grant
    Filed: December 12, 1997
    Date of Patent: April 10, 2001
    Assignee: Nisshinbo Industries, Inc.
    Inventors: Takaya Sato, Tsutomu Uehara, Hiroshi Yoshida
  • Patent number: 6214618
    Abstract: There is provided a method of making microcarrier beads having the steps of forming a bead made of a lightly crosslinked styrene copolymer core and also having functional groups on the surface of the bead and washing the microcarrier beads with basic and acidic solutions to make the beads compatible for cell culture. Also provided is a microcarrier bead made of a styrene copolymer core with a tri-methylamine exterior which has been washed in basic and acidic solutions to make the beads compatible for cell culture. The method of using microcarrier beads for increased growth of anchorage dependent cells having the steps of washing the microcarrier bead with basic and acidic solutions and mixing the microcarrier bead with an anchorage dependent cell containing culture medium is also provided.
    Type: Grant
    Filed: April 7, 1999
    Date of Patent: April 10, 2001
    Assignee: Solohill Engineering, Inc.
    Inventors: William J. Hillegas, David E. Solomon, Gilbert H. Wuttke
  • Patent number: 6150459
    Abstract: Synthetic comb copolymers which elicit controlled cellular response, methods of applying these polymers to various surfaces, and methods of using the polymers for modifying biomaterial surfaces, in tissue engineering applications and as drug delivery devices are provided. The comb copolymers are comprised of hydrophobic polymer backbones and hydrophilic, non-cell binding side chains which can be end-capped with cell-signaling ligands that guide cellular response. By mixing non-cell binding combs with ligand-bearing combs, the surface concentration and spatial distribution of one or more types of ligands, including adhesion peptides and growth factors, can be tuned on a surface to achieve desired cellular response. In one embodiment, the combs are used as stabilizing agents for dispersion polymerization of latexes. The comb-stabilized latexes can be applied to substrates by standard coating operations to create a bioregulating surface, or used as drug delivery agents.
    Type: Grant
    Filed: April 13, 1999
    Date of Patent: November 21, 2000
    Assignee: Massachusetts Institute of Technology
    Inventors: Anne M. Mayes, Linda G. Griffith, Darrell J. Irvine, Pallab Banerjee, Terry D. Johnson
  • Patent number: 6146892
    Abstract: Methods and compositions are described that provide three-dimensional fibrillar matrices useful as, among other things, structural prosthetics and scaffolds for cells. The porous fibrillar matrices of the present invention have desirable mechanical properties suitable to a variety of applications, including platforms for in vitro cell cultivation, implants for tissue and organ engineering, implants as tendon and facia prosthetics, and product packaging.
    Type: Grant
    Filed: September 28, 1998
    Date of Patent: November 14, 2000
    Assignee: The Regents of the University of Michigan
    Inventors: Peter X. Ma, Ruiyun Zhang
  • Patent number: 6143293
    Abstract: A three-dimensional scaffold for tissue generation. Mechanical fasteners allow layered and volumetric scaffold sections, which may be pre-seeded with cells and/or growth factors, to be assembled into a heterogeneous generated tissue for implantation.
    Type: Grant
    Filed: March 26, 1998
    Date of Patent: November 7, 2000
    Assignees: Carnegie Mellon, University of Pittsburgh
    Inventors: Lee E. Weiss, Jay Wynn Calvert
  • Patent number: 6140127
    Abstract: Endothelial cell attachment to an intravascular stent is promoted by coating the stent with an endothelial cell specific adhesion peptide. Coating is preferably carried out by activating the intravascular stent using plasma glow discharge, applying on the stent a layer or plurality of layers of a polymer such as poly(2-hydroxyethylmethacrylate), applying a tresylation solution containing pyridine and tresyl chloride, and applying a five amino acid peptide having the sequence glycine-arginine-glutamic acid-aspartic acid-valine.
    Type: Grant
    Filed: February 18, 1998
    Date of Patent: October 31, 2000
    Assignee: Cordis Corporation
    Inventor: Eugene A. Sprague
  • Patent number: 6133004
    Abstract: A bioreactor carrier is provided composed of a water absorption gel of a crosslinked N-vinylcarboxamide resin which has a great moisture content and excellent physical strength, is not eroded by microorganisms and is easily mass-produced on an industrial scale. The gel is obtained by swelling and gelling a crosslinked N-vinylcarboxamide resin made from an N-vinylcarboxamide such as N-vinylacetoamide. The swollen gel may be in the form of beads of 1.0 to 20 mm, and the resin when swollen with water has a water absorption coefficient of 500 to 3500%. Resin beads may be swollen in a suspension of a biocatalyst such as animal cells, plant cells, microorganisms or protozoans to bind and immobilize the biocatalyst to form a bioreactor. The microorganisms can be nitrate bacteria, denitrification bacteria or Hyphomycetes, and the bioreactor may be used to treat waste water or for deodorizing.
    Type: Grant
    Filed: March 9, 1998
    Date of Patent: October 17, 2000
    Assignee: Nisshinbo Industries, Inc.
    Inventors: Takaya Sato, Tsutomu Uehara, Hiroshi Yoshida
  • Patent number: 6103528
    Abstract: A gelling cell culture medium useful for forming a three dimensional matrix for cell culture in vitro is prepared by copolymerizing an acrylamide derivative with a hydrophilic comonomer to form a reversible (preferably thermally reversible) gelling linear random copolymer in the form of a plurality of linear chains having a plurality of molecular weights greater than or equal to a minimum gelling molecular weight cutoff, mixing the copolymer with an aqueous solvent to form a reversible gelling solution and adding a cell culture medium to the gelling solution to form the gelling cell culture medium. Cells such as chondrocytes or hepatocytes are added to the culture medium to form a seeded culture medium, and temperature of the medium is raised to gel the seeded culture medium and form a three dimensional matrix containing the cells. After propagating the cells in the matrix, the cells may be recovered by lowering the temperature to dissolve the matrix and centrifuging.
    Type: Grant
    Filed: April 17, 1998
    Date of Patent: August 15, 2000
    Assignees: Battelle Memorial Institute, Medical University of South Carolina
    Inventors: Yuehuei H. An, Vladimir A. Mironov, Anna Gutowska
  • Patent number: 6093558
    Abstract: Compositions and methods are provided for adhering and binding biologically active proteins and protein-containing composites to substrates. Adhesive formulations comprising a nonproteinaceous polymer of monomeric units comprising an aromatic moiety substituted with at least one hydroxyl group such as poly(p-hydroxy-styrene) are applied to substrates and subsequently contacted with proteins. Beads comprising a nonproteinaceous polymer of monomeric units comprising an aromatic moiety substituted with at least one hydroxyl group are also provided, and the beads are coated with a protein. Substrates to which the adhesive formulations have been applied, as well as the beads, can be used to adhere cells and tissues, to sort cell types, to perform immunoassays, to perform chromatography and to remove protein from samples.
    Type: Grant
    Filed: July 25, 1991
    Date of Patent: July 25, 2000
    Assignee: Edge Biosystems, Inc.
    Inventors: John Seed, Brian Seed
  • Patent number: 6039972
    Abstract: A conformable wound dressing is prepared by producing a sub-confluent layer of cultured mammalian cells such as epithelial cells anchored to a surface of a synthetic polymeric film which is hydrophobic, non-inhibitory to cell growth and non-cytotoxic. The polymer may be ethylene-vinyl acetate copolymer or a blend of ethylene-vinyl acetate copolymer and polystyrene, and is preferably subjected to corona discharge to improve cell attachment. The polymeric film may be sterilized with ethylene oxide or by gamma-irradiation. Preferably, the polymeric film is a continuous film containing apertures formed by perforation before or after cell culture to provide an apertured wound dressing. In a preferred embodiment, a laminate is formed containing a sub-confluent layer of mammalian cells anchored to a surface of a continuous film of synthetic polymer having a plurality of thin and thick portions cast on and supported by a carrier layer having a plurality of raised portions.
    Type: Grant
    Filed: January 20, 1998
    Date of Patent: March 21, 2000
    Assignee: Smith & Nephew PLC
    Inventors: Yvonne Margaret Barlow, Stephen Michael Lang
  • Patent number: 6001352
    Abstract: A method for stimulating chondrocyte proliferation and inhibiting chondrocyte differentiation along the endochondral developmental pathway is provided comprising contacting condrocytes with an effective amount of Platelet-Derived Growth Factor (PDGF) such as PDGF-BB, PDGF-AA OR PDGF-AB in the substantial absence of growth factors which promote cell differentiation. This allows such cells to be multiplied in culture for loading onto a scaffolding material and implanting into a cartilage or bone wound.
    Type: Grant
    Filed: March 31, 1997
    Date of Patent: December 14, 1999
    Assignee: OsteoBiologics, Inc.
    Inventors: Barbara D. Boyan, Zvi Schwartz
  • Patent number: 5981211
    Abstract: Methods of maintaining animal cells for product production, for supporting hepatocyte function and viability to treat a patient suffering from hepatic failure and for preserving tissue-specific function of mammalian cells are carried out with a bioreactor containing a feed and waste chamber and a cell chamber separated by a selectively permeable membrane. Within the cell chamber, a biocompatible contracted three-dimensional gel matrix entraps animal cells or genetic modifications thereof, and a liquid phase contains a concentrated solution of the cell product. The bioreactor uses only two chambers to achieve three distinct zones within the bioreactor. The bioreactor can be of either hollow fiber or flat-bed configuration. In the configuration using hollow fibers, the two fluid paths correspond to the cavity surrounding the hollow fibers (the extracapillary space), and to the lumens of the hollow fibers themselves. Both fluid paths have inlet and outlet ports.
    Type: Grant
    Filed: October 7, 1996
    Date of Patent: November 9, 1999
    Assignee: Regents of the University of Minnesota
    Inventors: Wei-Shou Hu, Frank Bernard Cerra, Scott Lyle Nyberg, Matthew Thomas Scholz, Russell A. Shatford
  • Patent number: 5976870
    Abstract: Disclosed is an improved artificial liver comprising a static liver-slice culture apparatus which is much more effective than a conventional hepatocyte bioreactor in removing toxins present in the plasma of a patient suffering from hepatic failure.
    Type: Grant
    Filed: January 14, 1998
    Date of Patent: November 2, 1999
    Inventor: Sung-Su Park
  • Patent number: 5849588
    Abstract: The present invention relates to a three-dimensional cell and tissue culture system. In particular, it relates to this culture system for the long term culture of liver cells and tissues in vitro in an environment that more closely approximates that found in vivo. The culture system described herein provides for proliferation and appropriate liver cell maturation to form structures analogous to tissue counterparts in vivo. The resulting liver tissues survive for prolonged periods, perform liver-specific functions, and maintain hepatic tissue architecture following in vivo implantation.The liver cultures have a variety of applications ranging from transplantation or implantation in vivo, to screening cytotoxic compounds and pharmaceutical compounds in vitro, to the production of biologically active molecules in "bioreactors" and to the construction of extracorporeal liver assist device.
    Type: Grant
    Filed: August 1, 1996
    Date of Patent: December 15, 1998
    Assignee: Advanced Tissue Sciences, Inc.
    Inventors: Brian A. Naughton, Gail K. Naughton
  • Patent number: 5843781
    Abstract: A device having a surface coated with a firmly adherent cell monolayer is produced by culturing adherent cells in the presence of the surface in vitro under conditions of continuous shear stress of from 0.4 dyne/cm.sup.2 to 33 dyne/cm.sup.2 produced by the force of circulating fluid medium in contact with the cells. The surface may be contained by an implantable device, or a culture or fermentation vessel. Preferably, an endothelial cell monolayer is produced on a surface of a prosthetic vascular device made of polypropylene. In a hollow fiber cartridge device, endothelial cells are grown under shear stress on the inner surface of the lumen of a hollow fiber and perivascular cells are grown on the outer surface of the fiber. Growing cells under continual stress more closely approximates the in vivo environment where blood passes over the endothelium in a blood vessel, and produces a cell monolayer closely resembling naturally occurring firmly adherent cell layers found in vivo in the lining of blood vessels.
    Type: Grant
    Filed: January 4, 1996
    Date of Patent: December 1, 1998
    Assignee: The Johns Hopkins University School of Medicine
    Inventors: Barbara J. Ballermann, Mark J. Ott
  • Patent number: 5837235
    Abstract: Bone and cartilage are regenerated in a patient by a process of removing fatty tissue such as omentum tissue from a patient, comminuting the tissue to form small tissue particles, suspending the particles in a liquid to form a suspension, depositing the suspension on a solid carrier to prepare a solid implanting material, implanting the implanting material in a patient in an environment favoring bone or cartilage formation, and regenerating bone or cartilage in the patient. The carrier can be demineralized bone, collagen, mineral material or synthetic polymer material in pulverulent, textile, porous particle or monolith form. A cell adhesion agent may be applied to the carrier or added to the suspension, and a growth factor may be deposited on the carrier. Comminuting is performed by digesting with an enzyme and/by mechanically comminuting. Liquid used to form the suspension may contain a gel precursor which is gelled after the suspension is deposited to the carrier.
    Type: Grant
    Filed: May 9, 1996
    Date of Patent: November 17, 1998
    Assignee: Sulzer Medizinaltechnik AG
    Inventors: Werner Mueller, Thomas Thaler
  • Patent number: 5773285
    Abstract: A method for culturing an organic tissue comprising: attaching the tissue onto an inner side of a mesh which is placed in an incubation chamber, and culturing the tissue in the presence of a culture medium and a gas containing oxygen under a condition that the ratio of the contact time of the tissue with the culture medium to that with the gas lies in a range from 1:2.5 to 1:3.5.
    Type: Grant
    Filed: November 9, 1995
    Date of Patent: June 30, 1998
    Inventor: Sung-Su Park
  • Patent number: 5712137
    Abstract: A conformable wound dressing is prepared by producing a sub-confluent layer of cultured mammalian cells such as epithelial cells anchored to a surface of a synthetic polymeric film which is hydrophobic, non-inhibitory to cell growth and non-cytotoxic. The polymer may be ethylene-vinyl acetate copolymer or a blend of ethylene-vinyl acetate copolymer and polystyrene, and is preferably subjected to corona discharge to improve cell attachment. The polymeric film may be sterilized with ethylene oxide or by gamma-irradiation. Preferably, the polymeric film is a continuous film containing apertures formed by perforation before or after cell culture to provide an apertured wound dressing. In a preferred embodiment, a laminate is formed containing a sub-confluent layer of mammalian cells anchored to a surface of a continuous film of synthetic polymer having a plurality of thin and thick portions cast on and supported by a carrier layer having a plurality of raised portions.
    Type: Grant
    Filed: May 8, 1995
    Date of Patent: January 27, 1998
    Assignee: Smith & Nephew PLC
    Inventors: Yvonne Margaret Barlow, Stephen Michael Lang
  • Patent number: 5709854
    Abstract: A cell-polymeric solution is injected into an animal where the polymer crosslinks to form a polymeric hydrogel containing dispersed cells and the cells form new tissue in the animal. The polymer is biodegradable and is a natural polymer such as alginate or a synthetic polymer. The cells are chondrocytes, osteoblasts, muscle cells, fibroblasts or cells acting primarily to synthesize, secret or metabolize materials. Crosslinking of the polymer results from using cations or anions, altering the pH or changing the temperature. A polyion such as polyethyleneimine or polylysine can be added before injection to stabilize the polymeric hydrogel. A kit for tissue formation is provided by combining the cell-polymeric solution with a means for injecting the solution into an animal.
    Type: Grant
    Filed: April 30, 1993
    Date of Patent: January 20, 1998
    Assignee: Massachusetts Institute of Technology
    Inventors: Linda Griffith-Cima, Anthony Atala, Charles A. Vacanti, Keith T. Paige
  • Patent number: 5691203
    Abstract: Animal adhesive cells, particularly human vascular endothelial cells, are cultured in serum-free condition by coating at least one polymer having cell adhesive activity on an inner surface of a culture vessel or surface of a carrier for cell culture, and culturing the cells in the coated vessel or with the coated carrier using a serum-free medium for animal cell culture containing isolated serum albumin, and preferably also transferrin. The polymer is a synthetic polymer modified with a peptide having cell adhesive activity or a natural polymer having cell adhesive activity or a combination thereof. Preferably, the peptide is RGDV, RGDS, RGDN, DGEA or YIGSR and the natural polymer is collagen, gelatin, keratin, fibronectin, vitronectin or laminin. A preferred medium for culturing human vascular endothelial cells is basal medium MCDB 131 or MCDB 107 containing isolated serum albumin, transferrin, hydrocortisone and epithelial growth factor.
    Type: Grant
    Filed: September 29, 1993
    Date of Patent: November 25, 1997
    Assignee: Kurashiki Boseki Kabushiki Kaisha
    Inventors: Susumu Katsuen, Kunihiro Ohshima, Ryohei Yamamoto, Toyokazu Nishino
  • Patent number: 5643561
    Abstract: Disclosed is a coating compositions for culturing animal adhesive cells comprising a water-insoluble polymer dissolved in a lower alcohol or an aqueous lower alcohol which enable to enhance the adhesive ability and growth of the adhesive cells. Also disclosed is serum-free cell culturing method using culture vessels or carrier coated with the water-insoluble polymer having cell adhesive activity on at least a part of the surface which enable to not only culture but also subculture a variety of adhesive cells including vascular endothelial cell under serum-free condition.
    Type: Grant
    Filed: November 2, 1994
    Date of Patent: July 1, 1997
    Assignee: Kurashiki Boseki Kabushiki Kaisha
    Inventors: Susumu Katsuen, Kunihiro Ohshima, Seiko Kawamura, Ryohei Yamamoto, Toyokazu Nishino
  • Patent number: 5602029
    Abstract: The substrate for cell culture to be used for cell arrangements is formed by applying a photoresist on a surface of a substrate, removing selective parts of the photoresist on the surface of the substrate by optical exposure and development, and forming an immobilized enzyme membrane on the surface of the substrate after removing the photoresist, and removing the photoresist after forming the immobilized enzyme membrane. An enzyme substrate of enzyme contained in the immobilized enzyme membrane is a material that is necessary for growth of cells for forming cell arrangements or is a material that inhibits growth of such cells, and a reaction product of oxygen contained in the immobilized enzyme membrane is a material that is necessary for growth of cells for forming cell arrangements or a material that inhibits growth of such cells. It is possible to control the cell adhesion on the surface of the substrate.
    Type: Grant
    Filed: June 22, 1995
    Date of Patent: February 11, 1997
    Assignee: NEC Corporation
    Inventor: Shigeyuki Miyamoto