Support Is A Membrane Patents (Class 435/401)
  • Publication number: 20040014212
    Abstract: The invention relates to a method of preparing a xenotransplantable porcine islet preparation capable upon xenotransplantation of producing porcine insulin in an appropriate recipient mammal, the method including or comprising: (i) harvesting the pancreas of piglets at or near full term gestation, and (ii) extracting islets from a culture of the harvested pancreas using a suitable collagenase, (iii) the culture of the harvested pancreas being a) of mechanically reduced harvested pancreas, and b) a supportive mammalian albumin substantially free of non-human microbiological agents,wherein (at least some stage in the method) the islets are associated with Sertoli cells.
    Type: Application
    Filed: June 25, 2003
    Publication date: January 22, 2004
    Inventors: Robert Bartlett Elliott, Guiseppe Basta, Giovanni Luca, Riccardo Calafiore
  • Publication number: 20040014214
    Abstract: The invention relates to a method for the production of a recipient-specific tissue transplant, consisting of a tissue matrix and recipient-acceptable cells populating said matrix. The transplant prepared and intended for populating is sterilized with hydrogen peroxide. Sterilization with hydrogen peroxide reliably prevents contamination while preserving the tissue base.
    Type: Application
    Filed: July 17, 2003
    Publication date: January 22, 2004
    Inventor: Augustinus Bader
  • Patent number: 6673339
    Abstract: The invention is directed to a prosthetic kidney, to methods of making a prosthetic kidney and to methods of treating kidney disease with a prosthetic kidney. The prosthetic kidney comprises nephron analogs on the exterior surface and an enclosed porous membrane structure equipped with an effluent channel for collecting and draining urine from the device. The nephron analogs are prepared by implanting a device containing renal tubule analogs on the membrane structures and inducing angiogenesis to form glomeruli-like structures. The renal tubule analogs are prepared by seeding kidney cells on the porous membrane structure and culturing this composite in vitro.
    Type: Grant
    Filed: May 26, 1999
    Date of Patent: January 6, 2004
    Assignee: Children's Medical Center Corporation
    Inventors: Anthony Atala, James J. Yoo, Samy Ashkar
  • Patent number: 6623963
    Abstract: A biocompatible, resorbable Type II collagen-based matrix is reconstituted from solubilized animal cartilage tissue and used in the culture and growth of cells, such as chondrocyte cells. The matrix is produced by isolating cartilage tissue, solubilizing and reconstituting the cartilage to form a fleece-like material, pressing the fleece-like material to form a sheet-like article, and sterilizing the article. An implantable article for cartilage repair includes chondrocyte cells retained on the matrix.
    Type: Grant
    Filed: December 20, 1999
    Date of Patent: September 23, 2003
    Assignees: Verigen AG
    Inventors: Peter Karl Müller, Peter Behrens, Bruno Giannetti, Jürgen Rohwedel, Martin Russlies
  • Patent number: 6616912
    Abstract: A bi-component microporous hollow fiber membrane structure is provided for in vivo propagation of cells and use in testing of the effect of medical treatments on cells within the structure. The structure has an inner structure fabricated from a first bio-compatible polymer and an outer structure fabricated from a different polymer that has a lower tendency for cell adhesion than the inner structure polymer. In this way, the inner structure can be selected to optimize cell propagation and the outer structure can be fabricated from a polymer which optimizes the removal of the bi-component structure from its implanted location. The inner and outer structures may have a pore size between 10 and 1000 Angstroms and 100 and 2000 Angstroms, respectively, and be formed from polysulfone or polyether sulfone and polyvinyledene difuoride, respectively. The membrane structure can form macrocapsules containing media and living cells for implanting.
    Type: Grant
    Filed: January 5, 2001
    Date of Patent: September 9, 2003
    Assignee: Spectrum Laboratories, Inc.
    Inventors: Roy T. Eddleman, Jesus Martinez
  • Patent number: 6607910
    Abstract: A two-chamber perfusion bioreactor counteracts a significant amount of shear stress while allowing high nutrient transfer and removal of waste and/or valuable bio-products, e.g., protein, hormones, growth factors, and monoclonal antibodies without disturbing the cell culture. Cells and tissues, contained in the growth chamber, are suspended in the growth media by rotation of the vessel and are separated by a porous membrane from the feeding chamber. Nutrients and gases are transferred across the membrane from the feeding chamber to the growth chamber. Even dispersion of nutrients along the membrane barrier is accomplished through a novel nutrient dispersion flow path. The flow path is created by flowing media out a center shaft in the vessel and along the front of the nutrient dispersion disk. The fluid then flows around the back of the nutrient dispersion disk and exits the outer center return shaft.
    Type: Grant
    Filed: November 13, 2000
    Date of Patent: August 19, 2003
    Assignee: Synthecon, Inc.
    Inventors: S. Dan Dimitrijevich, Charlie W. Dodd, William J. Anderson, Ray P. Schwarz
  • Patent number: 6541023
    Abstract: Use of collagen of aquatic origin for the production of supports for tissue engineering is disclosed. The collagen may be obtained from fish skin, preferably in its native form. Novel tissue engineering supports with a low risk of contamination are produced.
    Type: Grant
    Filed: July 14, 2000
    Date of Patent: April 1, 2003
    Assignee: Coletica
    Inventors: Valérie Andre, Nabil Abdul Malak, Alain Huc
  • Publication number: 20030044970
    Abstract: The present invention provides an apparatus and methods to evaluate invasive potential of tumor cells. The apparatus permits culturing, staining and analysis of test samples to be performed on the same test plate to facilitate cell invasiveness tests. Methods for testing cell invasiveness in vitro are described.
    Type: Application
    Filed: June 13, 2001
    Publication date: March 6, 2003
    Inventors: Kehan Han, Kedu Han
  • Patent number: 6511798
    Abstract: Cell based screens for studying drug transport are described and improved methods for the preparation of cell monolayers for use in such screens are disclosed.
    Type: Grant
    Filed: March 16, 1999
    Date of Patent: January 28, 2003
    Assignee: Zeneca Limited
    Inventor: Charles Michael Shaw
  • Publication number: 20030008388
    Abstract: Provided is a cell culture apparatus for culturing cells, and optionally, for performing magnetic separation of cells desired to be cultured. The cell culture apparatus preferably comprises a frame; at least one gas permeable membrane securedly sealed in a leak-proof sealing to a frame and an opposing surface comprising a rigid surface in forming a culture chamber therebetween; and at least one resealable aperture to allow substances to be introduced into, or withdrawn from, the culture chamber.
    Type: Application
    Filed: June 25, 2002
    Publication date: January 9, 2003
    Applicant: BioCrystal, Ltd.
    Inventors: Emilio Barbera-Guillem, M. Bud Nelson
  • Patent number: 6492119
    Abstract: A macro array comprises a film-shaped hard porous body and a plurality of spots, which contain test substances and are arrayed on the film-shaped hard porous body. The film-shaped hard porous body may be constituted of a surface layer region, which is provided with through-pores having a comparatively small mean pore diameter, and a base layer region, which is provided with through-pores having a comparatively large mean pore diameter. The surface of the film-shaped hard porous body, on which surface the spots are to be arrayed, may be coated with an auxiliary substance for promoting fixation of the test substances to the surface of the film-shaped hard porous body.
    Type: Grant
    Filed: September 18, 2000
    Date of Patent: December 10, 2002
    Assignee: Fuji Photo Film Co., Ltd.
    Inventor: Masashi Ogawa
  • Patent number: 6485969
    Abstract: A composition comprising follicle basement membrane is described. The composition can be utilized as a cell culture substrate for proliferating cells in vitro.
    Type: Grant
    Filed: June 22, 2000
    Date of Patent: November 26, 2002
    Assignee: Purdue Research Foundation
    Inventors: Elikplimi K. Asem, John J. Turek, J. Paul Robinson
  • Patent number: 6482645
    Abstract: The present invention describes methods for producing artificial fascial slings and their subsequent use in treating subjects with urinary incontinence. The invention is based, in part, on the discovery that mesenchymal cells that secrete elastin and collagen, extracellular proteins responsible for elasticity and strength, respectively, can be used to engineer artificial fascia in vitro.
    Type: Grant
    Filed: March 5, 2002
    Date of Patent: November 19, 2002
    Assignee: Children's Medical Center Corporation
    Inventor: Anthony Atala
  • Patent number: 6479252
    Abstract: Provided is a cell culture apparatus for culturing cells, and optionally, for performing magnetic separation of cells desired to be cultured. The cell culture apparatus preferably comprises a frame; two membranes, preferably each being gas permeable, which are securedly sealed in a leak-proof selaing to a frame in forming a culture chamber there-between; and at least one resealable aperture to allow substances to be introduced into, or withdrawn from, the culture chamber.
    Type: Grant
    Filed: November 28, 2000
    Date of Patent: November 12, 2002
    Assignee: BioCrystal, Ltd.
    Inventors: Emilio Barbera-Guillem, M. Bud Nelson
  • Patent number: 6472202
    Abstract: A loading station assembly for at least partially supporting the underside of a flexible cell membrane positioned in the bottom of a cell culture well. The assembly includes a planar member having a plurality of apertures. Each aperture receives a post having a flange which supports the membrane. A central opening defined in the planar member allows a vacuum to be drawn therethrough and to pull a portion of the membrane downwardly and cause a central portion of the membrane to stretch across the flange. Cells cultured on the membrane are subjected to a corresponding strain.
    Type: Grant
    Filed: September 29, 2000
    Date of Patent: October 29, 2002
    Assignee: Flexcell International Corporation
    Inventor: Albert J. Banes
  • Patent number: 6465252
    Abstract: The invention features modular cell culturing devices including one or more flat-plate modules, and is based on the discovery that if the flows of liquid medium and oxygenated fluid are separated by a gas-permeable, liquid-impermeable membrane, and the cells are grown attached to the liquid side of the membrane, the device can be used to culture cells with transport of oxygen through the membrane (i.e., direct oxygenation), without regard for the flow rate of the liquid medium passing through the device. The new flow-through cell culturing devices can thus be used to culture cells, e.g., hepatocytes, with high levels of cell function in organ, e.g., liver, assist systems, for production of cells, for production of cell-derived products, such as, proteins or viruses, or for systems to treat biological liquids to remove toxins, such as, ammonia, or add cell-synthesized products, or both.
    Type: Grant
    Filed: June 21, 2000
    Date of Patent: October 15, 2002
    Assignees: The General Hospital Corporation, Organogenesis Inc.
    Inventors: Mehmet Toner, Arno W. Tilles, Ulysses J. Balis, Martin L. Yarmush, Maury D. Cosman, Paul A. Dimilla
  • Patent number: 6455310
    Abstract: Provided is a cell culture apparatus for culturing cells, and optionally, for performing magnetic separation of cells desired to be cultured. The cell culture apparatus preferably comprises a frame; two membranes, preferably each being gas permeable, which are securedly sealed in a leak-proof selaing to a frame in forming a culture chamber therebetween; and at least one resealable aperture to allow substances to be introduced into, or withdrawn from, the culture chamber.
    Type: Grant
    Filed: March 15, 2000
    Date of Patent: September 24, 2002
    Assignee: BioCrystal Ltd.
    Inventor: Emilio Barbera-Guillem
  • Patent number: 6426214
    Abstract: Cell encapsulating devices capable of maintaining large numbers of viable cells are provided containing an inert, substantially cell-free core that displaces cells, a permeable membrane and a zone for maintaining cells. The permeable membrane surrounds the core such that the zone of cells is bounded by the core and the permeable membrane. A preferred device contains a polytetrafluoroethylene permeable membrane and a flexible polymer core having a plurality of ridges and valleys running lengthwise along the core. The cell zone may contain support means for cell attachment and the core may have an outer boundary containing a material that promotes cell adhesion. Preferably, the cell zone has a thickness such that at least about 10% of the cells, more preferably at least about 50% or 80%, in a cell layer located closest to the outer boundary of the core remain viable. The thickness is preferably less than 500 microns such as 25 to 250 microns or 50 to 100 microns.
    Type: Grant
    Filed: November 8, 1999
    Date of Patent: July 30, 2002
    Assignee: Gore Enterprise Holdings, Inc.
    Inventors: Mark D. Butler, Stanley L. Mish
  • Patent number: 6410309
    Abstract: Provided is a cell culture apparatus for culturing cells, and optionally, for performing magnetic separation of cells desired to be cultured. The cell culture apparatus preferably comprises a frame; at least one gas permeable membrane securedly sealed in a leak-proof sealing to a frame and an opposing surface comprising a rigid surface in forming a culture chamber therebetween; and at least one resealable aperture to allow substances to be introduced into, or withdrawn from, the culture chamber.
    Type: Grant
    Filed: November 28, 2000
    Date of Patent: June 25, 2002
    Assignee: BioCrystal LTD
    Inventors: Emilio Barbera-Guillem, M. Bud Nelson
  • Patent number: 6368859
    Abstract: The present invention describes methods for producing artificial fascial slings and their subsequent use in treating subjects with urinary incontinence. The invention is based, in part, on the discovery that mesenchymal cells that secrete elastin and collagen, extracellular proteins responsible for elasticity and strength, respectively, can be used to engineer artificial fascia in vitro.
    Type: Grant
    Filed: December 29, 1999
    Date of Patent: April 9, 2002
    Assignee: Children's Medical Center Corporation
    Inventor: Anthony Atala
  • Patent number: 6358730
    Abstract: A filtration assembly can comprise a chamber for holding a fluid sample to be filtered and a cover assembly defining a petri dish into which a filter element can be placed for cultivating microorganisms present on the filter element. A filtration assembly can also comprise a sample reservoir for holding a fluid sample and a base for supporting the sample reservoir detachably connected to the sample reservoir. One of the sample reservoir and the base can have a projection extending around its periphery and the other of the sample reservoir and the base can have a groove extending around its periphery and detachably engaging the projection in a fluid-type manner around its periphery. A filtration assembly can also comprise a sample reservoir for holding a fluid sample to be filtered and a base for supporting the sample reservoir. The base can include a fluid port and communication with an interior of the sample reservoir and a skirt surrounding the fluid port for contact with a vacuum manifold.
    Type: Grant
    Filed: July 26, 1999
    Date of Patent: March 19, 2002
    Assignee: Pall Corporation
    Inventor: Jeffrey Kane
  • Patent number: 6319712
    Abstract: The invention relates to a biohybrid articular surface replacement in the form of a three-dimensional, porous carrier, in which cartilage cells can be cultured in vitro and/or in vivo to a three-dimensional cell union and which following cell growth and optionally after tissue development, can be placed on the exposed bone in the vicinity of a defective articular surface, wherein on the side of the carrier intended for engagement with the bone it has an agent for aiding osseous integration.
    Type: Grant
    Filed: January 26, 1999
    Date of Patent: November 20, 2001
    Assignee: Deutsche Institute fur Textil-und Faserforschung Stuttgart
    Inventors: Norbert M. Meenen, Martin Dauner, Heinrich Planck
  • 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
  • Patent number: 6297046
    Abstract: A multi-layer, flexible, gas-permeable film (10) suitable for forming a cell culture container (20), the film (10) comprising a first layer (12) composed of a polystyrene having a thickness within the range of 0.0001 inches to about 0.0010 inches and, a second layer (14) adhered to the first layer (12) composed of a polyolefin having a thickness within the range of 0.004 inches to about 0.015 inches.
    Type: Grant
    Filed: October 28, 1994
    Date of Patent: October 2, 2001
    Assignee: Baxter International Inc.
    Inventors: Sidney T. Smith, David V. Bacehowski, William Kolanko, Larry Rosenbaum, Stephen L. Smith, James G. Bender, Lecon Woo, Michael T. K. Ling
  • Publication number: 20010014473
    Abstract: Cartilage tissue and implants comprising tissue are produced in vitro starting from cells having the ability to form an extracellular cartilage matrix. Such cells are brought into a cell space (1) and are left in this cell space for producing an extracellular cartilage matrix. The cells are brought into the cell space to have a cell density of ca. 5×107 to 109 cells per cm3 of cell space. The cell space (1) is at least partly separated from a culture medium space (2) surrounding the cell space by means of a semi-permeable wall (3) or by an open-pore wall acting as convection barrier. The open-pore wall can be designed as a plate (7) made of a bone substitute material and constituting the bottom of the cell space (1). The cells settle on such a plate (7) and the cartilage tissue growing in the cell space (1).
    Type: Application
    Filed: April 18, 2001
    Publication date: August 16, 2001
    Applicant: Sulzer Orthopedics Ltd.
    Inventors: Franz Rieser, Werner Muller, Pedro Bittmann, Pierre Mainil-Varlet, Christoph P. Saager
  • Patent number: 6242248
    Abstract: A bioreactor (10) has arranged within its internal chamber (14) a bundle of liquid-impermeable hollow tubes (16), which are used to freeze or vitrify a biologically active material seeded within the internal chamber. When the bioreactor is ready for use, the biologically active material may be thawed by perfusing the liquid-impermeable hollow tubes with a heated solution or heated vapor.
    Type: Grant
    Filed: February 8, 2000
    Date of Patent: June 5, 2001
    Assignee: Cedars-Sinai Medical Center
    Inventors: Jacek Rozga, Achilles A. Demetriou
  • Patent number: 6218182
    Abstract: A tissue engineering bioreactor is disclosed for growing three-dimensional tissue. Cells are seeded onto a mesh and provided with two media flows, each contacting a different side of the cells. The media flows contain different concentrations of nutrients, allowing nutrients to be delivered to the cells by diffusion gradient. The bioreactor can be used to grow liver tissue, and designed as an extracorporeal liver assist device in which blood or plasma is exposed to the three-dimensional liver tissue. The blood or plasma from a patient directed to flow against the liver tissue. The liver tissue is further exposed on its opposite side to media providing nutrients and gases. The device provides porous boundaries between the blood or plasma, tissue, and media; allowing nutrient and protein delivery by diffusion gradient to dialyze a patient's blood.
    Type: Grant
    Filed: December 21, 1999
    Date of Patent: April 17, 2001
    Assignee: Advanced Tissue Sciences
    Inventors: Brian A. Naughton, Craig R. Halberstadt, Benson Sibanda
  • Patent number: 6214574
    Abstract: A culturing system and method particularly useful for producing cellular products such as viral pathogens of cells. It includes a mass transfer culture segment, stacked filter plates to adjust the medium composition, and a product removal and concentration segment. The mass transfer culture segment utilizes changed directional flow of the medium to maximize cell growth and production of product. The stacked filter plates allow addition of sterile fresh medium and removal of growth inhibitory substances.
    Type: Grant
    Filed: September 15, 1999
    Date of Patent: April 10, 2001
    Inventor: Henry B. Kopf
  • Patent number: 6204056
    Abstract: A patient replica is created from layered culture medium where solid culture medium is formed so that a discontinuity exists, for example, between layers of culture medium or between culture medium and the container holding the medium. An injection port is provided in registration with the discontinuity so that a sample of patient blood can be infused into the discontinuity to form a thin layer of blood in contact with a surface of culture medium. The thin layer of blood obviates the requirement for any anticoagulant allowing blood-borne pathogens to be readily cultured without using broth. Further antibiotics or other drug samples may be placed on an exposed surface of the culture medium above the blood layer so that the antibiotic can diffuse through the culture medium and reveal the sensitivities of the cultured pathogens.
    Type: Grant
    Filed: September 3, 1999
    Date of Patent: March 20, 2001
    Inventors: Allen C. Barnes, Janice S. Barnes
  • Patent number: 6197061
    Abstract: The present invention is directed to a transplantable cartilage matrix and a method for its in vitro production.
    Type: Grant
    Filed: March 1, 1999
    Date of Patent: March 6, 2001
    Inventors: Koichi Masuda, Eugene J-M. A. Thonar, Michael Hejna
  • 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: 6121042
    Abstract: An apparatus and method for sterilizing, seeding, culturing, storing, shipping, and testing three-dimensional tissue constructs is disclosed. The apparatus includes a fluid reservoir, a pump, at least one treatment chamber, and a means for controlling media flow characteristics around a tissue construct disposed within the treatment chamber, and for controlling movement of the construct itself, so as to simulate a variety of physiologic conditions. One exemplary embodiment of the invention includes a means for applying an axial stress to the construct. Applying an axial stress to the construct during seeding and culturing results in a tissue-engineered construct with cells and their fibers oriented in a manner which is more likely to possess long term dimensional stability and the patency of native vessels with normal physiologic function.
    Type: Grant
    Filed: December 31, 1997
    Date of Patent: September 19, 2000
    Assignee: Advanced Tissue Sciences, Inc.
    Inventors: Alvin Peterson, Lee K. Landeen, John Bennett, Jason Gee, Scott Chesla, Joan Zeltinger, James H. Flatt, Mark A. Applegate, Noushin Dunkelman, Stephen V. Kemmerrer
  • 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: 6060306
    Abstract: An apparatus and method for sterilizing, seeding, culturing, storing, shipping, and testing cartilage constructs is disclosed. The apparatus generally includes a treatment chamber and a means for varying the fluid flow and pressure within the treatment chamber during seeding and culturing. The application of pressure to the cartilage construct improves both the uniformity of seeding throughout the construct and facilitates the flow of nutrients to and removal of waste products from cells embedded in the construct. In this manner, a tissue-engineered cartilage construct with cells and their fibers oriented in a manner which is more likely to possess long term dimensional stability and the patency of cartilage with normal physiologic function may be formed.
    Type: Grant
    Filed: August 14, 1997
    Date of Patent: May 9, 2000
    Assignee: Advanced Tissue Sciences, Inc.
    Inventors: James H. Flatt, Mark A. Applegate, Alvin Peterson
  • Patent number: 6054311
    Abstract: After the cryopreservation of living cells, the cells in a post-thaw recovery stage are supported by a gas permeable medium. This medium comprises at least one polyfluorinated compound. This compound may be gassed, for example with oxygen where oxygenation is required.
    Type: Grant
    Filed: December 18, 1997
    Date of Patent: April 25, 2000
    Assignee: F2 Chemicals Limited
    Inventors: Michael Raymond Davey, Kenneth Charles Lowe, John Brian Power
  • Patent number: 6043079
    Abstract: The present invention provides an apparatus and methods for incubating cells which rely on the use of a semipermeable membrane placed between two planar members, at least one planar member having an aperture.
    Type: Grant
    Filed: May 7, 1996
    Date of Patent: March 28, 2000
    Assignee: Joseph Leighton
    Inventor: Joseph Leighton
  • Patent number: 6042909
    Abstract: The invention features an empty device for receiving a bioactive agent. The device includes a biocompatible and semi-permeable membrane that defines an enclosed space; the membrane also has at least one end that defines an opening for introducing the bioactive agent into the enclosed space. The device is configured to be placed in an animal.In one embodiment of the invention, the membrane has an inner surface and an outer surface, where the inner surface defines the inner surface, and includes a biocompatible adhesive in the general region of the opening to allow sealing of the opening after the introduction of the bioactive agent into the enclosed space.Another embodiment of the invention includes a biocompatible frame mounted in supporting relationship to the membrane and defining an opening for introducing the bioactive agent into the enclosed space. The frame has greater porosity than the membrane.
    Type: Grant
    Filed: September 3, 1997
    Date of Patent: March 28, 2000
    Assignee: Circe Biomedical, Inc.
    Inventors: Karen E. Dunleavy, Timothy J. Perlman, Kerry A. Gagnon, Claudy J. P. Mullon
  • Patent number: 6037171
    Abstract: A compact arrangement for cell culture is provided by sandwiching a grid matrix containing a multiplicity of perforations therethrough between a planar base and a semipermeable membrane such that the perforations define microchambers for cell culture. The perforations may be in a regular patten such as a honeycomb pattern, and be circular to form microchambers having a diameter of approximately 0.2 to 5 mm. A magnet means can be used to hold the sandwich structure together by placing a magnet on a side of the base opposite the grid matrix and a magnetically attractable film on a side of the membrane opposite the grid matrix. The base may have a diameter of approximately 5 to 20 cm, and be coated with a layer such as an agarose layer lacking cell affinity. A spot surface that forms an island having cell affinity is placed on the layer centrally within each perforation.
    Type: Grant
    Filed: May 4, 1998
    Date of Patent: March 14, 2000
    Assignee: Microcloning CCCD AB
    Inventor: Borg Larsson
  • Patent number: 6027938
    Abstract: A patient replica is created from a layered culture medium where solid culture medium is formed so that a discontinuity exists between the layers. An infusion port is provided in registration with the discontinuity so that a fresh unadulterated sample of patient blood can be infused into the discontinuity to form a thin layer of blood between the layers of culture medium. The thin layer obviates the requirement for any anticoagulant allowing blood-borne pathogens to be readily cultured without using broth. Further antibiotics or other drug samples may be placed on the surface of the culture medium above the blood layer so that the antibiotic can diffuse through the culture medium and reveal the sensitivities of the cultured pathogens. Other samples of pathogens or tissues can be placed on the surface of the culture medium so that effects of drugs or growth factors present in the patient blood can be observed thereby allowing the entrapped blood layer to act as a biological replica of the patient.
    Type: Grant
    Filed: March 20, 1998
    Date of Patent: February 22, 2000
    Inventors: Allen C. Barnes, Janice S. Barnes
  • Patent number: 6017760
    Abstract: A perfusion device such as a liver assist device containing a housing defining a perfusion inlet and a perfusion outlet, a porous membrane structure mounted within said housing to define a perfusion compartment and an adjacent hepatocyte compartment, and porcine hepatocytes isolated from a porcine liver by retrograde perfusion.
    Type: Grant
    Filed: October 10, 1995
    Date of Patent: January 25, 2000
    Assignee: Rhode Island Hospital
    Inventors: Hugo O. Jauregui, Sharda Naik, Henry Santangini, Donna M. Trenkler
  • Patent number: 6008049
    Abstract: A tissue engineering bioreactor is disclosed for growing three-dimensional tissue. Cells are seeded onto a mesh and provided with two media flows, each contacting a different side of the cells. The media flows contain different concentrations of nutrients, allowing nutrients to be delivered to the cells by diffusion gradient. The bioreactor can be used to grow liver tissue, and designed as an extracorporeal liver assist device in which blood or plasma is exposed to the three-dimensional liver tissue. The blood or plasma from a patient directed to flow against the liver tissue. The liver tissue is further exposed on its opposite side to media providing nutrients and gases. The device provides porous boundaries between the blood or plasma, tissue, and media, allowing nutrient and protein delivery by diffusion gradient to dialyze a patient's blood.
    Type: Grant
    Filed: August 19, 1998
    Date of Patent: December 28, 1999
    Assignee: Advanced Tissue Sciences, Inc.
    Inventors: Brian A. Naughton, Craig R. Halberstadt, Benson Sibanda
  • Patent number: 5980889
    Abstract: Cell encapsulating devices capable of maintaining large numbers of viable cells are provided containing an inert, substantially cell-free core that displaces cells, a permeable membrane and a zone for maintaining cells. The permeable membrane surrounds the core such that the zone of cells is bounded by the core and the permeable membrane. The cell zone may contain a support means for cell attachment and the core may have an outer boundary containing a material that promotes cell adhesion. Preferably, the cell zone has a thickness such that at least about 10% of the cells, more preferably at least about 50% or 80%, in a cell layer located closest to the outer boundary of the core remain viable. The thickness is preferably less than 500 microns such as 25 to 250 microns or 50 to 100 microns. The devices are suitable for implantation into an individual in need of treatment and are capable of supplying therapeutic substances to such individuals.
    Type: Grant
    Filed: August 5, 1997
    Date of Patent: November 9, 1999
    Assignee: Gore Hybrid Technologies, Inc.
    Inventors: Mark D. Butler, Stanley L. Mish
  • 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: 5962250
    Abstract: The invention provides exemplary testing devices, systems, and methods for evaluating the permeation of various chemicals through different types of cells. In one exemplary embodiment, a testing device is provided which comprises a plate defining at least one well having an open top end. At least one membrane is insertable into the well in a generally vertical orientation to divide the well into separate chambers. The membrane is removable from the well to allow the cells to be grown on the membrane before insertion into the well.
    Type: Grant
    Filed: October 28, 1997
    Date of Patent: October 5, 1999
    Assignee: Glaxo Group Limited
    Inventors: Robert M. Gavin, Harold E. Selick, Gregory A. Smith
  • Patent number: 5837234
    Abstract: A bioartificial organ for implanting to provide a therapeutic effect is prepared containing a core of living cells encapsulated in a foam-like membrane having three regions: a dense, fine-pored, permselective inner region, a middle region that lacks macrovoids and a fine-pored outer region. The membrane has a molecular weight cutoff that permits passage to nutrients to the cells but not passage of the cells. Preferably, the membrane is made of polyether sulfone, pores range in size between 0.02 .mu.m and 2.0 .mu.m and have polyhedrally symmetric boundaries and are arranged asymmetrically from one surface to the other. The membrane has an asymmetry factor AF relative to the maximum pore diameter of 0.01 to 2.0 and a ratio of the maximum mean free path length to the diameter of the largest pore of greater than 3. The membrane can be hydrophobic or hydrophilic. The bioartificial organ is formed by coextrusion or by stepwise assembly by forming the cell core and then applying the membrane.
    Type: Grant
    Filed: June 7, 1995
    Date of Patent: November 17, 1998
    Assignee: CytoTherapeutics, Inc.
    Inventors: Frank T. Gentile, Shelley R. Winn, Michael Lysaght, Ulrich Baurmeister, Friedbert Wechs, Henning Rottger
  • Patent number: 5807672
    Abstract: Fragments of nucleic acids derived from an appropriate mycobacteria genome, particularly Mycobacterium tuberculosis, their applications in the diagnosis of mycobacteria infections, as well as plasmides containing said fragments. The nucleotidic sequence is comprised of a nucleotidic sequence repeated in the genome of a mycobacterium and specific of the bacillus of tuberculosis and is characterized by a strong hybridation with M. tuberculosis.
    Type: Grant
    Filed: June 7, 1995
    Date of Patent: September 15, 1998
    Assignee: Institut Pasteur
    Inventors: Jean-Luc Guesdon, Dominique Thierry, Agnes Ullman, Brigitte Gicquel, Anne Brisson-Noel
  • Patent number: 5792603
    Abstract: An apparatus and method for sterilizing, seeding, culturing, storing, shipping, and testing vascular grafts is disclosed. Specifically, the present invention relates to an apparatus and method for seeding and culturing vascular grafts with human cells. The apparatus includes a fluid reservoir, a pump, an alternating pressure source, and at least one treatment chamber. By alternating pressure to a support structure within the treatment chamber upon which a vascular graft scaffold is positioned, a varying radial stress is placed on the scaffold. In an alternative embodiment, fluid is pumped directly through the vascular graft subjecting the vascular graft to radial and shear stresses. Applying shear and/or radial stresses to the vascular graft during seeding and culturing simulates physiological conditions.
    Type: Grant
    Filed: June 27, 1996
    Date of Patent: August 11, 1998
    Assignee: Advanced Tissue Sciences, Inc.
    Inventors: Noushin Dunkelman, Alvin E. Peterson, Lee Kevin Landeen, Joan Zeltinger
  • Patent number: 5792653
    Abstract: In an apparatus for culturing cells which comprises a plate-like body with a lattice structure having openings separated from one another by sidewalls and a bottom disposed on one side of the lattice structure and having passages permeable for liquids but not for cells so as to form, with the lattice structure, cavities for receiving cells to be grown therein, the cavities have a clear width of between 50 .mu.m and 1000 .mu.m and the bottom consists of a material to which cells placed into the cavities will not easily attach so that the cells grow from the side walls of the cavities causing them to form a three-dimensional cell structure.
    Type: Grant
    Filed: January 31, 1994
    Date of Patent: August 11, 1998
    Assignee: Kernforschungszenlrum Karlsruhe GmbH
    Inventors: Karl Friedrich Weibezahn, Gudrun Knedlitschek, Hermann Dertinger, Klaus Schubert, Thomas Schaller, Wilhelm Bier
  • Patent number: 5786215
    Abstract: An apparatus and method for the in vitro culturing of animal cells, e.g., mammalian cells, to attain mass growth of the cells per se and/or to recover cell-secreted products of interest therefrom, in which an integral culture and gassing element is formed from spirally-wound or concentricallywrapped lengths of a liquid-impermeable, oxygen-permeable membrane envelope such that narrow cell culture spaces are formed between adjacent windings or wrapping of the envelope. Cells in the culture spaces, which spaces may optionally contain cell substrate material, are cultured in contact with a culture medium introduced into the spaces from an end of the element, and in contact with oxygen-containing gas supplied to the membrane envelope for diffusion across its oxygen-permeable walls into the culture spaces.
    Type: Grant
    Filed: May 8, 1995
    Date of Patent: July 28, 1998
    Assignee: Baxter International Inc.
    Inventors: Peter C. Brown, Mark T. Wininger, Robert V. Oakley
  • Patent number: 5786216
    Abstract: A biocompatible capsule for containing cells for implantation is prepared containing an inner support that provides tensile strength to the capsule. The capsule may be a tubular semipermeable membrane such as a hollow fiber membrane having both ends sealed. A rod shaped inner support extends through the lumen and ends of the rod are attached to sealed ends of the fiber. Prior to sealing one fiber end, cells are introduced into the lumen. Cells within the capsule may be suspended in a liquid medium or immobilized in a hydrogel or extracellular matrix material, and biologically active molecules can be delivered from the capsule to surroundings or from the surroundings into the capsule. The inner support may have external features such as flutes or a roughened or irregularly-shaped surface, and may be coated with cell-adhesive substance or a cell-viability-enhancing substance.
    Type: Grant
    Filed: November 10, 1994
    Date of Patent: July 28, 1998
    Assignee: Cytotherapeutics, Inc.
    Inventors: Keith E. Dionne, Orion D. Hegre, Thomas R. Flanagan, Tyrone F. Hazlett, Edward J. Doherty