Cell and tissue culture container

Information

  • Patent Grant
  • 11555172
  • Patent Number
    11,555,172
  • Date Filed
    Friday, September 14, 2018
    5 years ago
  • Date Issued
    Tuesday, January 17, 2023
    a year ago
  • Inventors
  • Original Assignees
  • Examiners
    • Bowers; Nathan A
    Agents
    • Cha; Don D.
    • HDC Intellectual Property Law, LLP
Abstract
The invention generally relates to containers for cell and tissue culturing with multiple compartments in fluid communication with each other to provide a common culture environment in each of the compartments while maintaining physical separation of cells and tissue therein. The invention further relates to culture containers providing a sterile culture environment with detachably coupleable lids and open access to each compartment within a container.
Description
FIELD OF THE INVENTION

The invention generally relates to cell and tissue culture devices.


BACKGROUND

While certain tissues in the human body, such as skin, are capable of self-repair (e.g., wound healing), there are many tissues that are not. For example, articular cartilage has no innate ability to repair itself, rendering any damage thereto permanent. Articular cartilage lines opposing bone surfaces in diarthrodial joints and provides a smooth, lubricated surface for articulation. Accordingly, defects in articular cartilage tend to expand and worsen over time. Damage to the articular cartilage in joints such as the knee can lead to debilitating pain.


Typical treatment choices, depending on lesion and symptom severity, are rest and other conservative treatments, minor arthroscopic surgery to clean up and smooth the surface of the damaged cartilage area, and other surgical procedures such as microfracture, drilling, and abrasion. All of these may provide symptomatic relief, but the benefit is usually only temporary, especially if the person's pre-injury activity level is maintained. For example, severe and chronic forms of knee joint cartilage damage can lead to greater deterioration of the joint cartilage and may eventually lead to a total knee joint replacement. Approximately 200,000 total knee replacement operations are performed annually. The artificial joint generally lasts only 10 to 15 years and the operation is, therefore, typically not recommended for people under the age of fifty.


An alternative treatment is implantation of cultured neo-cartilage (i.e., immature hyaline cartilage) which can be grown in-vitro to a desired size and shape on a 3D scaffold from chondrocyte cells biopsied from the patient (autologous) or from another individual (heterologous). Examples of this process are described, for example, in U.S. Pat. Nos. 6,949,252; 7,537,780; 7,468,192; 7,217,294; and U.S. patent application Ser. No. 14/208,931. An exemplary method for 3D culture of neo-cartilage is shown in FIG. 8 and includes the steps of isolating chondrocyte cells from a biopsy, 2D growth of cells, seeding of a 3D scaffold, and two culturing steps. The first culturing step takes place under controlled pressure, oxygenation, and perfusion conditions to mimic the joint environment while the second culturing step is a 3D static culture.


Along with the neo-cartilage for implantation, multiple other surrogate tissues are simultaneously cultured in the same vessel in order to permit pre-implantation testing and verification procedures without damaging the neo-cartilage to be implanted.


Current culture containers include narrow opening flask-type containers with a sealing cap with a gas-permeable filter membrane but the 3D static culture procedure presents multiple challenges which are unmet by current culture containers. For example, the surrogates and the neo-cartilage to be implanted need to be cultured in the same conditions in a common fluid to enable validation through surrogate testing. However, in current containers, the surrogates and neo-cartilage can grow into one another as they mature and then require separation which can damage the cells and scaffolds. Another problem stems from the fact that the tissues must be submerged in fluid during the 3D static culture but the buoyancy of the cultures varies during tissue growth. The 3D static culture process takes 2 weeks and requires incubation throughout the process, taking up space in expensive incubators and limiting production efficiency and capacity using bulky flask-type containers. Additionally, the surrogates and the neo-cartilage to be implanted must be transferred from one container to another during the 2 week process and then must be removed from the container before final packaging for distribution and implantation. Manipulation of the neo-cartilage to be implanted and the surrogates through the narrow opening of the current culture containers is difficult and can cause damage to the cells. These challenges are not unique to 3D static culturing of neo-cartilage and apply to a variety of cell and tissue culturing procedures.


SUMMARY

The invention relates to containers for cell and tissue culturing with multiple compartments in fluid communication with each other to provide a common culture environment in each of the compartments while maintaining physical separation of cells and tissue therein. Culture containers of the invention can be used to simultaneously culture one or more surrogate tissues alongside and under the same conditions as a tissue to be implanted, thereby enabling destructive testing and verification procedures to be carried out without harming the tissue to be implanted. Each compartment may contain the same type of tissue or different tissue types in order to investigate interactions between different tissue types. In some instances multiple tissue types may be cultured in a single compartment. The containers of the present invention provide containers for culturing these tissues in a common environment and fluid while preventing the surrogate tissues and the tissue for implantation from adhering or growing onto the container or each other and potentially damaging the tissue for implantation. Containers of the invention may provide sealing lids with gas permeable membranes to allow for gas exchange between the interior and exterior environments of the container while maintaining a sterile internal environment. The culture containers and lids may be configured to minimize height while maintaining adequate interior volume and maximizing incubator efficiency and space. Containers of the invention may also provide multiple compartments in fluid communication yet capable of restricting movement of and various sizes of sometimes buoyant tissue cultures and other materials. Additionally, culture containers of the invention may provide a large opening with easy, lid-off access to each compartment and any tissue or other materials therein. The several features of the containers of invention provide a more efficient platform for culturing and verifying cells and tissues for implantation while minimizing the potential for damage to the implantable tissue.


Culture containers of the invention may comprise a bottom wall and at least one side wall coupled thereto. Side walls may form right angles with the bottom wall or may taper out to provide a large opening with easy access to the compartments therein. Culture containers can be a cylinder, a cuboid, a triangular prism, a pentagonal prism, an octagonal prism or a variety of other 3 dimensional shapes.


Containers of the invention may include one or more interior walls which can divide the interior volume of the container into two or more compartments. A container may have 11 or more compartments or as few as two. The compartments may be of the same size or a variety of sizes. In some instances a larger compartment may be configured to contain cultured tissue for implantation while several smaller compartments may be sized to contain surrogates for testing.


In certain aspects, the container may comprise multiple components such as a first unit comprising a bottom wall and at least one side wall and a second unit comprising one or more of the interior walls or partition so that the partition may be removed from the container providing a single compartment or inserted into the container to provide multiple compartments therein. In certain instances, a single first component comprising the one or more side walls and the bottom wall may be compatible with multiple different second components comprising interior walls in various configurations so that, by interchanging second components, the number of compartments may be varied.


In order to achieve fluid communication between the compartments of the container, the interior walls may have openings including pores, slits, or gaps between an interior wall and a side wall, the bottom wall, or the lid. The openings may be dimensioned so as to allow fluid to pass between the compartments of the container without allowing cells, tissues, or 3D scaffolds to pass therebetween. Screens or filters may be used to cover openings in order to help restrict passage of cells, tissues, or 3D scaffolds therethrough.


Devices of the invention may include a lid configured to detachably couple to the top edge of the one or more side walls in order to enclose the container. The lid can generally correspond in shape and size to the opening formed by the top edge of the one or more side walls. The lid may be configured to form an air or water-tight seal when detachably coupled to the container, may include a gasket to aid in sealing, and may be secured via complementary threads, interlocking tabs, or other means. Preferably, the lid and the container may be detachably coupled without the use of tools in order to promote sterility and relatively easily in order to avoid excessive motion of the contained fluid and disruption of the cultured materials.


The lid may comprise a vent and/or a gas permeable membrane of a size and shape configured to allow gas to pass into and out of a sealed container while restricting undesirable particles such as bacteria, endotoxins, and other contaminants. The lid may be configured so that, when detachably coupled to the container, the only avenue for gas exchange between the interior and exterior of the container is through the filter. A filter may also be located on a side wall of the container.


Containers of the invention may be sized so that containers may contain an adequate volume of fluid (e.g., 500 mL) while maintaining sufficient space between the fluid and the lid to avoid contact during movement of the container and so that multiple containers can fit on a standard incubator tray to maximize space efficiency during the incubation process.


The lid, the container, or components thereof may comprise a variety of materials including, for example, polypropylene, high-density polyethylene, polystyrene, styrene-acrylonitrile (SAN), polycarbonatestyrene-maleic anhydride (SMA), cyclic olefin copolymers (COC), acrylic, acrylic-polyvinyl chloride alloys, polypropylene copolymers, polysulfone, polymethylpentene, or cellulosic. The lid, the container, or components thereof may comprise a substantially transparent material to allow visual inspection of the container's contents from outside of the container. Containers and lids may be configured as single-use disposables or may be configured for repeated use and sterilization.


In some aspects, the interior surface of the bottom wall, the interior surface of the one or more side walls, and/or the surfaces of the one or more interior walls may be smooth; textured with ridges, valleys, pores, or dimples; and/or treated with an agent to deter adherence of cultured cells or tissues and/or the facilitate retrieval from the container by scooping under the cultured tissue with a retrieval tool.





BRIEF DESCRIPTION OF THE DRAWINGS


FIG. 1 shows a side view of an exemplary embodiment of a circular multi-compartment culture container of the invention.



FIG. 2 shows a top view of an exemplary embodiment of a circular multi-compartment culture container of the invention.



FIG. 3 shows a top view of an exemplary embodiment of a rectangular multi-compartment culture container of the invention.



FIG. 4 shows a close up view of a single compartment of an exemplary embodiment of a circular multi-compartment culture container.



FIG. 5A shows a side view of an exemplary embodiment of a lid for a circular culture container.



FIG. 5B shows a top view of an exemplary embodiment of a lid for a circular culture container.



FIGS. 6A and 6B show an exemplary embodiment of a two component multi-compartment circular culture container.



FIG. 7 shows an exemplary embodiment of interlocking tabs.



FIG. 8 shows an exemplary method for 3D culture of neo-cartilage for implantation.





DETAILED DESCRIPTION

The invention relates to culture containers comprising multiple compartments configured to be in fluid communication with each other while maintaining physical separation of cell or tissues being cultured therein. Cells and tissues are cultured on 3D scaffolds to form tissues of a desired shape and size. If a tissue is being cultured for implantation, it is advantageous to simultaneously culture one or more surrogate tissues under the same conditions to enable destructive testing and verification procedures to be carried out without harming the tissue to be implanted. The containers of the present invention provide containers for culturing these tissues in a common environment and fluid while preventing the surrogate tissues and the tissue for implantation from adhering or growing onto the container or each other and potentially damaging the tissue for implantation. In various embodiments, each compartment in a container may contain the same type of tissue or different tissue types in order to investigate effects of different types of tissue on each other in a shared culture environment. In certain instances multiple tissue types may be cultured in a single compartment to investigate physical interactions between the tissues. Culture containers of the invention may be used to culture a variety of cells and tissues including chondrocytes, mesenchymal stem cells, fibroblasts, osteocytes, osteoblasts, synoviocytes, induced pluripotent stem cells (iPSC), embryonic stem cells (ESC), lymphocytes, adipocytes, myofibroblasts, hepatocytes, islet cells, monocytes, endometrial regenerative cells, or cancer stem cells. Applications for these containers include the culturing of neo-cartilage from chondrocytes for repair of articular cartilage defects.


Culture containers of the invention may comprise a bottom wall and at least one side wall coupled thereto. Side walls can be coupled to the bottom wall so that the side wall's planar surface is substantially transverse to the planar surface of the bottom wall. The culture container may have any number of side walls including 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 side walls. Side walls may be substantially straight or may be curved. The bottom wall may be a variety of shapes including, rectangular, circular, triangular, or pentagonal. The bottom wall shape should correspond to the number of side walls. For example, a container 101 with circular bottom wall 105 would comprise a single side wall 109, with a curved planar surface so that the bottom edge of the single side wall 109 forms a circle of substantially equal radius to that of the bottom wall 105 to which it is coupled as shown in FIG. 1. Alternatively, a container may have 4 straight side walls 109 coupled to a substantially rectangular bottom wall 105 as shown in FIG. 3. In embodiments having more than one side wall 109, the side walls may be coupled together at a vertical edge to form a corner as shown in FIG. 3.


Containers of the invention may include one or more interior walls which can divide the interior volume of the container into two or more compartments. Interior walls may be curved or straight and can be coupled to the bottom wall so that their planar surface is substantially transverse to the planar surface of the bottom wall. Interior walls can be coupled to the same planar surface of the bottom wall as the side walls. Interior walls may be coupled to one or more side walls and/or one or more other interior walls. A culture container may have any number of interior walls, including 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 interior walls and may comprise any number of compartments including 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or 11 compartments.



FIG. 1 illustrates an exemplary embodiment of a circular, multi-compartment culture container 101 having a circular bottom wall 105 and a single, curved side wall 109. The container 101 has a single curved interior wall 107, coupled to the bottom wall 105 to define a cylindrical center compartment 103. The container 101 also has several straight interior walls 107 coupled to both the curved side wall 109 and the curved interior wall 107, forming spokes and defining 10 smaller radial compartments 103 for a total of 11 compartments 103.



FIG. 2 illustrates a birds-eye view of the circular, multi-compartment culture container 101 of FIG. 1, having 10 compartments 103 defined by a curved side wall 109, a curved interior wall 107 and 10 straight interior walls 107.



FIG. 3 shows a birds-eye view of an exemplary container 103 having a rectangular bottom wall and 4 side walls 109 defining 8 compartments including 1 larger compartment 103 and 7 smaller compartments.


The larger center compartment 103 of the containers 101 shown in FIGS. 1-3 may be sized to contain a larger piece of tissue for implantation while smaller surrogate tissues may be contained in the smaller surrounding compartments 103.


In certain aspects, the container may comprise multiple components such as a first unit comprising a bottom wall and at least one side wall and a second unit comprising one or more of the interior walls or partition so that the partition may be removed from the container providing a single compartment or inserted into the container to provide multiple compartments therein. One or more of the components may have slots or other physical mechanisms configured to accept a portion of the other component. FIGS. 6A and 6B depict an exemplary embodiment of a multi-component container. A first component 120 is shown in FIG. 6A comprising a single, curved side wall 109 coupled at its bottom edge to a circular bottom wall 105. FIG. 6B illustrates a second component 130 comprising a single, circular interior wall 107 and 10 straight interior walls 107 extending radially therefrom. The second component 130 is configured to be placed within the first component 120 in order to separate the interior volume of the first component into 10 compartments. The second component 130 may be dimensioned so that the radial edges of the straight side walls 107 form a tight fit with the inner planar surface of the curved side wall 109 when the two components are combined.


In certain instances, a single first component comprising the one or more side walls and the bottom wall may be compatible with multiple different second components comprising interior walls in various configurations so that, by interchanging second components, the number of compartments may be varied.


The first component may include a stop 125 as illustrated in FIG. 6A configured to prevent the bottom edge of the interior walls 107 from contacting the interior planar surface of the bottom wall 105.


In order to achieve fluid communication between the compartments of the container, the interior walls may have openings. In certain embodiments the openings may be dimensioned so as to allow fluid to pass between the compartments of the container without allowing cells, tissues, or 3D scaffolds to pass therebetween. In some aspects an interior wall may be perforated with one or more holes or pores. In such instances, each hole should have a diameter smaller than the largest dimension of the cell, tissue, or 3D scaffold being cultured within a compartment defined in part by that interior wall. For example, for 3D tissue culture scaffolds having a 4 mm diameter by 1.5 mm thickness, openings in the interior walls may have diameters less than 4 mm as the scaffolds should be unable to pass through an opening with a diameter less than 4 mm. In certain aspects, an interior wall may comprise a slit of a certain length and width. In such instances, one of the length or the width of the slit should be less than the smallest dimension of the cell, tissue, or 3D scaffold being cultured within a compartment defined in part by that interior wall. For example, using 3D tissue culture scaffolds having a 4 mm diameter by 1.5 mm thickness, the length or width of the slit may be any value so long as the other dimension is less than 1.5 mm.


Openings may be located at a variety of positions within an interior wall including near the center, top, or sides of an interior wall. Openings may be uniformly or differentially located on each interior wall. In certain instances, an opening in an interior wall may be located near the bottom wall of the container. Cell and tissue cultures may rest on the bottom wall of the container during the culturing process. Openings near the bottom wall can allow for the exchange, between compartments, of fluid, nutrients, growth factors, and other particles at the tissue level. Particles that may tend to settle to the bottom may be better exchanged through openings near the bottom wall, thus better replicating the culture environment across compartments.



FIG. 4 illustrates an exemplary embodiment of a compartment 103 within a larger, cylindrical container such as the container 101 illustrated in FIG. 1. The compartment 103 in FIG. 4 is defined by a portion of a curved side wall 109, a portion of a curved interior wall 107, two straight interior walls 107, and a portion of a circular bottom wall 105. Each of the interior walls 107 has one or more openings 115 near the bottom wall enabling the passage of fluid between the compartment 103 and other, surrounding compartments (not shown). As noted above, the openings 115 may be dimensioned to allow fluid to pass through but to restrict the passage of the cultured cell or tissue within the compartment 103. In certain aspects, openings between compartments, in interior walls, may be covered by screens or filters configured to restrict inter-compartment passage of cells tissues or 3D scaffolds. In such instances the screen or filter may be of a biocompatible material and configured, by material, conformation, or surface treatment, to deter adherence of a cell or tissue thereto during the culturing process.


Interior walls and side walls may be substantially the same height relative to the bottom wall. In some aspects, the interior walls may have a height, relative to the bottom wall, that is less than the height of the side wall, relative to the bottom wall. In such instances, cell-culture medium or other fluid may be added to the container to a level, h, greater than the height of the interior walls but less than the height of the side walls so that the compartments are in fluid communication with each other. In certain aspects, one or more of the interior walls may be coupled to the side walls but not coupled to the bottom wall, leaving a gap between the bottom edge of the one or more interior walls and the planar surface of the bottom wall. This gap can be sized to allow fluid to pass between the compartments of the container without allowing cells, tissues, or 3D scaffolds to pass therebetween. In multi-component embodiments such as illustrated in FIGS. 6A and 6B, the stop 125 may be spaced from the bottom wall 125 so that, when the components are combined, a gap is left between the bottom edge of the one or more interior walls and the planar surface of the bottom wall. This gap can be sized to allow fluid to pass between the compartments of the container without allowing cells, tissues, or 3D scaffolds to pass therebetween. Fluid can be added to a level above or below the height of the interior walls. Fluid may be maintained at a level below the height of the interior walls in order to maintain separation of 3D scaffolds, cells, and tissues that may float to the surface of a fluid during culturing.


In certain embodiments, devices of the invention include a lid configured to detachably couple to the top edge of the one or more side walls in order to enclose the container. The lid can generally correspond in shape and size to the bottom wall. In embodiments where the one or more side walls taper in or out from the edges of the bottom wall, the lid may be smaller or larger than the bottom wall and can generally correspond to the shape and size formed by the top edge of the one or more side walls. The lid may be configured to form an air or water-tight seal when detachably coupled to the container. In certain aspects, a lid and a container may comprise complementary or interlocking threads so that the lid may be screwed down onto the upper edge of the at least one side wall. In some embodiments the lid or the upper edge of the at least one side wall may comprise a recess configured to accept a gasket wherein the gasket is compressed when the lid is detachably coupled to the container and may thereby form a seal. The gasket may be constructed from any suitable material including rubber, plastic, metal, nylon, neoprene, or cork. In certain aspects, a lid may detachably couple to a container through engagement of interlocking tabs on the lid and container. Interlocking tabs may include snap-fit style cantilever prong and recess type connections as well as screw-type interlocking tabs. FIG. 7 illustrates an exemplary style of interlocking tab wherein the lid or the container may include a block 312 while the other includes a receptacle 310 configured to receive and lock in the block 312. The interlocking tabs illustrated in FIG. 7 may be engaged by pushing the lid onto the container and then twisting the lid relative to the container so that the block 312 is inserted down and then into the receptacle 310 as illustrated by the arrow in FIG. 7.


In certain aspects, the one or more side walls of a container may be coupled to the bottom wall of the container at substantially right angles and/or the container configured so that the opening at the top of the container has an area substantially equal to the area of the bottom wall. An opening may thusly be configured to provide unfettered access to each compartment within the container from directly above to facilitate manipulation of materials within each compartment without interference from a tapered or flask-like neck or opening.


In some aspects, a lid may comprise a vent and/or a gas permeable membrane of a size and shape configured to allow gas to pass into and out of a sealed container while restricting undesirable particles such as bacteria, endotoxins, and other contaminants. The lid may be configured so that, when detachably coupled to the container, the only avenue for gas exchange between the interior and exterior of the container is through the filter. The filter may have a variety of reference pore sizes including 0.2 to 3 gm such as 0.2, 0.5, 1, 1.5, 2, 2.5, or 3 gm. The filter may be of a variety of different materials such as cellulose, nylon, polytetrafluorethylene, polydimethylsiloxane (PDMS silicone), or glass fiber. Commercially available filter materials include, for example, ePTFE membrane from W. L. Gore & Associates, Inc., 555 Paper Mill Road, Newark, Del. 19711. A filter may also be located on a side wall of the container.



FIGS. 5A and 5B show an exemplary embodiment of a lid 201 according to the invention. The lid 201 is substantially circular and configured to detachably couple to a substantially cylindrical container such as the container 101 shown in FIG. 1, 2, or 6A. The lid shown in FIGS. 5A and 5B comprises a circular filter 203 placed in the center of the lid. A lid filter may be part of a vent mechanism which includes a cap covering the filter material so that gas is vented through the side of the vent and the filter material is protected from fluid splashing. The lid shown in FIGS. 5A and 5B also comprises a downward facing lip with threads 205 on the interior surface thereof configured to interact with complementary threads on an exterior surface of a curved side wall of a container to provide a sealed compression through a screw-type mechanism. FIG. 5B shows a gasket 207, held in a recess of the lid and configured to be compressed against the upper edge of a curved side wall of a container. In certain aspects, the top of the lid and/or the bottom of the container may be configured with interlocking tabs and/or spacers to allow for controlled stacking of containers wherein the top container is spaced above the bottom container so that a filter on the bottom container's lid is still exposed to the exterior atmosphere.


In certain embodiments, a container of the invention may be sized so that multiple containers may fit on a 7 inch by 14 inch incubator tray. A container may be sized to contain a certain volume of fluid including at least 1, 10, 50, 100, 250, 500, 750, or 1000 mL. In an exemplary embodiment, a container 101 of the type illustrated in FIGS. 1 and 2 may have an outer diameter of 6 inches while the curved side wall 109 has a height of 2 inches and the interior walls 107 have a height of 1.5 inches and the single, curved interior wall forms a compartment 103 with an inside diameter of 3.5 inches. In an exemplary embodiment of a container of the type illustrated in FIG. 3, the container 101 has outside dimensions of 5 inches by 5 inches and the 4 side walls 109 have a height of 2 inches while the interior walls have a height of 1.5 inches. The interior walls 107 form one 3.75 inch by 3.75 inch compartment 103 and 7 1.25 inch by 1.25 inch compartments. In both of the above embodiments, two of the specified containers may fit on a single 7 inch by 14 inch incubator tray.


In certain embodiments, the lid, the container, or components thereof may comprise a variety of materials. Materials may be biocompatible, endotoxin-free, and/or configured to be sterilized to a variety of Sterility Assurance Levels (SAL) including 10−1, 10−2, 10−3, 10−4, 10−5, or 10−6, for example. In some embodiments, the lid, container, and/or components thereof may comprise a USP Class N, V, or VI material, including, for example, polypropylene, high-density polyethylene, polystyrene, styrene-acrylonitrile (SAN), polycarbonatestyrene-maleic anhydride (SMA), cyclic olefin copolymers (COC), acrylic, acrylic-polyvinyl chloride alloys, polypropylene copolymers, polysulfone, polymethylpentene, or cellulosic. The lid, the container, or components thereof may comprise a substantially transparent material to allow visual inspection of the container's contents from outside of the container. Containers and lids may be configured as single-use disposables or may be configured for repeated use and sterilization. Containers and lids can comprise materials which are nonreactive to standard cell culture media such as EMEM or DMEM.


In some aspects, the interior surface of the bottom wall, the interior surface of the one or more side walls, and/or the surfaces of the one or more interior walls may be smooth; textured with ridges, valleys, pores, or dimples; and/or treated with an agent to deter adherence of cultured cells or tissues and/or the facilitate retrieval from the container by scooping under the cultured tissue with a retrieval tool. In certain aspects, the interior surface of the side walls, interior walls, and/or bottom wall, may be treated with an anti-microbial agent or other instrument to prevent microbial growth and/or contamination.


The lid, the container, or components thereof may be produced by a variety of known means including extrusion, injection molding, blow molding, or rotational molding. The container may be formed from a single piece of material or from multiple pieces which are subsequently coupled together. The lid may be similarly formed. Where constructed from multiple pieces, the pieces maybe joined a variety of known techniques including welding, or bonding using a bonding agent such as a biocompatible adhesive.


In a preferred embodiment, the lid, container, or components thereof are made using thermoforming. In thermoforming, a sheet of material, such as polystyrene is heated until pliable and then formed to a desired shape using a mold. Vacuum pressure may be used to conform the material to the mold. The material may then be cooled to regain rigidity, and then removed from the mold. The resulting product may then be trimmed or otherwise finished to remove excess material or rough edges.


In some aspects, the lid, container, or portions thereof may be formed using injection molding. In injection molding, a mold block with a hollow cavity in shape of the desired product is coupled to a reservoir that can inject molten plastic resin is made. The mold is made in two halves such that a completed part can be removed from one of the halves without any portion being impeded by portions of the mold cavity. The mold is placed in a processing machine capable of clamping the two halves of the mold together. Molten plastic resin is injected into the cavity at high pressure in order to facilitate rapidly filling thin or distant volumes of the mold.


INCORPORATION BY REFERENCE

References and citations to other documents, such as patents, patent applications, patent publications, journals, books, papers, web contents, have been made throughout this disclosure. All such documents are hereby incorporated herein by reference in their entirety for all purposes.


EQUIVALENTS

Various modifications of the invention and many further embodiments thereof, in addition to those shown and described herein, will become apparent to those skilled in the art from the full contents of this document, including references to the scientific and patent literature cited herein. The subject matter herein contains important information, exemplification and guidance that can be adapted to the practice of this invention in its various embodiments and equivalents thereof.

Claims
  • 1. A method for culturing a tissue comprising: providing a container comprising a bottom wall coupled to a bottom edge of at least one side wall, and an at least one interior wall coupled to the at least one side wall to define at least a first compartment and a second compartment within the container, wherein the at least one interior wall comprises a bottom edge that does not contact the bottom wall, leaving a gap between the bottom wall and the at least one interior wall, wherein the gap allows fluid to pass between the first and second compartments without allowing cells, tissues, or 3D scaffolds to pass therebetween;providing a lid comprising a gas-permeable membrane, wherein the lid is configured to be detachably coupled to a top edge of the at least one side wall;introducing a first living cell of a first cell type to the first compartment and a second living cell of a second cell type to the second compartment in the presence of a cell culture medium;exposing the container to conditions promoting cell growth to produce a first tissue from the first living cell and a second tissue from the second living cell.
  • 2. The method of claim 1, wherein the first cell type or the second cell type is a chondrocyte, mesenchymal stem cell, fibroblast, osteocyte, osteoblast, synoviocyte, induced pluripotent stem cell (iPSC), embryonic stem cell (ESC), lymphocyte, adipocyte, myofibroblast, hepatocyte, islet cell, monocyte, endometrial regenerative cell, or cancer stem cell.
  • 3. The method of claim 2, wherein the first cell type is a chondrocyte.
  • 4. The method of claim 3, wherein the first tissue is neo-cartilage.
  • 5. The method of claim 2, wherein the second cell type is a chondrocyte.
  • 6. The method of claim 5, wherein the second cell type is neo-cartilage.
  • 7. The method of claim 1, wherein the first living cell or the second living cell is present on the bottom wall of the container.
  • 8. The method of claim 1, wherein the exposing step comprises adding a fluid to a level below the height of the at least one interior wall.
  • 9. The method of claim 1, further comprising seeding a 3D scaffold with the first living cell and introducing the 3D scaffold seeded with the first living cell into the first compartment.
  • 10. The method of claim 1, further comprising preparing the first tissue for implantation into a human body.
  • 11. The method of claim 1, further comprising performing testing on the second tissue to verify viability of the first tissue.
  • 12. The method of claim 1, wherein the lid or the container comprises polypropylene, high-density polyethylene, polystyrene, styrene-acrylonitrile (SAN), polycarbonatestyrene-maleic anhydride (SMA), cyclic olefin copolymers (COC), acrylic, acrylic-polyvinyl chloride alloys, polypropylene copolymers, polysulfone, polymethylpentene, or cellulosic.
  • 13. The method of claim 1, wherein the container comprises a circular bottom wall, a circular lid, and a single, curved sidewall coupled thereto to form a substantially cylindrical shape.
  • 14. The method of claim 1, wherein the container comprises at least 3 compartments.
  • 15. The method of claim 1, wherein the at least one side wall has a first height relative to the bottom wall that is substantially equal to a second height of the at least one interior wall relative to the bottom wall.
  • 16. The method of claim 1, wherein the gas-permeable membrane comprises a 0.2 micron filter.
  • 17. The method of claim 1, wherein the container is configured to hold at least 500 mL of fluid.
CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a divisional of U.S. patent application Ser. No. 14/558,080, filed Dec. 2, 2014, which is herein incorporated by reference in its entirety.

US Referenced Citations (822)
Number Name Date Kind
3400199 Balassa Sep 1968 A
3476855 Balassa Nov 1969 A
3478146 Balassa Nov 1969 A
3551566 Thiels Dec 1970 A
3772432 Balassa Nov 1973 A
3791930 Saxholm Feb 1974 A
3867728 Stubstad et al. Feb 1975 A
3966908 Balassa Jun 1976 A
4060081 Yannas et al. Nov 1977 A
4172128 Thiele Oct 1979 A
4182655 Hartmeier Jan 1980 A
4201845 Feder et al. May 1980 A
4280954 Yannas et al. Jul 1981 A
4296100 Franco Oct 1981 A
4350629 Yannas et al. Sep 1982 A
4378347 Franco Mar 1983 A
4394370 Jefferies Jul 1983 A
4400833 Kurland Aug 1983 A
4442655 Stroetmann Apr 1984 A
4448718 Yannas et al. May 1984 A
4458678 Yannas et al. Jul 1984 A
4479271 Botesky et al. Oct 1984 A
4501289 Bagby Feb 1985 A
4505286 Yannas et al. Mar 1985 A
4522753 Yannas et al. Jun 1985 A
4522811 Eppstein et al. Jun 1985 A
4582865 Balazs et al. Apr 1986 A
4600574 Lindner et al. Jul 1986 A
4609551 Caplan et al. Sep 1986 A
4627853 Campbell et al. Dec 1986 A
4642120 Nevo et al. Feb 1987 A
4656137 Balassa Apr 1987 A
4681763 Nathanson et al. Jul 1987 A
4683195 Mullis et al. Jul 1987 A
4683202 Mullis Jul 1987 A
4713448 Balazs et al. Dec 1987 A
4736866 Leder et al. Apr 1988 A
4757017 Cheung Jul 1988 A
4776173 Kamarei et al. Oct 1988 A
4776853 Klement et al. Oct 1988 A
4795467 Piez et al. Jan 1989 A
4801299 Brendel et al. Jan 1989 A
4837379 Weinberg Jun 1989 A
4846835 Grande Jul 1989 A
4851354 Winston et al. Jul 1989 A
4870009 Evans et al. Sep 1989 A
4873191 Wagner et al. Oct 1989 A
4873192 Kunkel Oct 1989 A
4880429 Stone Nov 1989 A
4880610 Constantz Nov 1989 A
4902508 Badylak et al. Feb 1990 A
4904259 Itay Feb 1990 A
4912032 Hoffman et al. Mar 1990 A
4932973 Gendler Jun 1990 A
4950296 McIntyre Aug 1990 A
4950483 Ksander et al. Aug 1990 A
4955911 Frey et al. Sep 1990 A
4963146 Li Oct 1990 A
4963489 Naughton et al. Oct 1990 A
4965188 Mullis et al. Oct 1990 A
4971954 Brodsky et al. Nov 1990 A
4976738 Frey et al. Dec 1990 A
4978355 Frey et al. Dec 1990 A
4981783 Augenlicht Jan 1991 A
4994559 Moscatelli et al. Feb 1991 A
5002071 Harrell Mar 1991 A
5002583 Pitaru et al. Mar 1991 A
5007934 Stone Apr 1991 A
5010892 Colvin et al. Apr 1991 A
5032508 Naughton et al. Jul 1991 A
5041138 Vacanti et al. Aug 1991 A
5053049 Campbell Oct 1991 A
5053050 Itay Oct 1991 A
5067963 Khouri et al. Nov 1991 A
5067964 Richmond et al. Nov 1991 A
5071436 Huc et al. Dec 1991 A
5073373 O'Leary et al. Dec 1991 A
5084051 Tormala et al. Jan 1992 A
5087963 Kaneda et al. Feb 1992 A
5092867 Harms et al. Mar 1992 A
5092887 Gendler Mar 1992 A
5118512 O'Leary et al. Jun 1992 A
5152791 Hakamatsuka et al. Oct 1992 A
5155214 Baird et al. Oct 1992 A
5191067 Lappi et al. Mar 1993 A
5195892 Gersberg Mar 1993 A
5206023 Hunziker Apr 1993 A
5206028 Li Apr 1993 A
5226914 Capian et al. Jul 1993 A
5227147 Yoshimura et al. Jul 1993 A
5236456 O'Leary et al. Aug 1993 A
5256140 Fallick Oct 1993 A
5256476 Tanaka et al. Oct 1993 A
5260420 Burouf-Radosevich et al. Nov 1993 A
5270197 Yayon et al. Dec 1993 A
5270300 Hunziker Dec 1993 A
5275826 Badylak et al. Jan 1994 A
5281265 Liu Jan 1994 A
5281422 Badylak et al. Jan 1994 A
5284155 Treadwell et al. Feb 1994 A
5290558 O'Leary et al. Mar 1994 A
5298254 Prewett et al. Mar 1994 A
5302702 Seddon et al. Apr 1994 A
5306304 Gendler Apr 1994 A
5306311 Stone et al. Apr 1994 A
5306500 Rhee et al. Apr 1994 A
5310883 Seddon et al. May 1994 A
5314476 Prewett et al. May 1994 A
5326357 Kandel Jul 1994 A
5329846 Bonutti Jul 1994 A
5336616 Livesey et al. Aug 1994 A
5338772 Bauer et al. Aug 1994 A
5352463 Badylak et al. Oct 1994 A
5352589 Bergonzoni et al. Oct 1994 A
5354557 Oppermann et al. Oct 1994 A
5356629 Sander et al. Oct 1994 A
5356883 Kuo et al. Oct 1994 A
5368858 Hunziker Nov 1994 A
5372821 Badylak et al. Dec 1994 A
5380328 Morgan Jan 1995 A
5410016 Hubbell et al. Apr 1995 A
5411885 Marx May 1995 A
5425769 Snyders, Jr. Jun 1995 A
5439684 Prewett et al. Aug 1995 A
5439818 Fiddes et al. Aug 1995 A
5443950 Naughton et al. Aug 1995 A
5445833 Badylak et al. Aug 1995 A
5464439 Gendler Nov 1995 A
5466462 Rosenthal et al. Nov 1995 A
5471893 Newbigging Dec 1995 A
5474987 Cohen et al. Dec 1995 A
5475052 Rhee et al. Dec 1995 A
5491220 Seddon et al. Feb 1996 A
5496722 Goodwin et al. Mar 1996 A
5507813 Dowd et al. Apr 1996 A
5510396 Prewett et al. Apr 1996 A
5512460 Nauro et al. Apr 1996 A
5513682 Morse et al. May 1996 A
5516532 Atala et al. May 1996 A
5516533 Badylak et al. May 1996 A
5522753 McGraw Jun 1996 A
5545222 Bonutti Aug 1996 A
5549904 Juergensen et al. Aug 1996 A
5554389 Badylak et al. Sep 1996 A
5556430 Gendler Sep 1996 A
5565519 Rhee et al. Oct 1996 A
5569272 Reed et al. Oct 1996 A
5569584 Augenlicht Oct 1996 A
5571721 Turner Nov 1996 A
5571895 Kurokawa et al. Nov 1996 A
5576288 Lappi et al. Nov 1996 A
5604293 Fiddes et al. Feb 1997 A
5606793 Gross et al. Mar 1997 A
5607474 Athanasiou et al. Mar 1997 A
5614496 Dunstan et al. Mar 1997 A
5614587 Rhee et al. Mar 1997 A
5616568 Pouyani et al. Apr 1997 A
5618551 Tardy et al. Apr 1997 A
5618925 Dupont et al. Apr 1997 A
5622928 Naruo et al. Apr 1997 A
5624463 Stone et al. Apr 1997 A
5629191 Cahn May 1997 A
5630842 Brodniewicz May 1997 A
5630982 Boring May 1997 A
5631011 Wadstrom May 1997 A
5632745 Schwartz May 1997 A
5650176 Lee et al. Jul 1997 A
5653730 Hammerslag Aug 1997 A
5656492 Glowacki et al. Aug 1997 A
5656598 Dunstan et al. Aug 1997 A
5662710 Bonutti Sep 1997 A
5676976 Lee et al. Oct 1997 A
5679637 Lappi et al. Oct 1997 A
5681353 Li et al. Oct 1997 A
5683461 Lee et al. Nov 1997 A
5686431 Cohen et al. Nov 1997 A
5695998 Badylak et al. Dec 1997 A
5700476 Rosenthal et al. Dec 1997 A
5700774 Hattersley et al. Dec 1997 A
5707962 Chen et al. Jan 1998 A
5713374 Pachence et al. Feb 1998 A
5718413 Walter et al. Feb 1998 A
5723331 Tubo et al. Mar 1998 A
5728159 Stroever et al. Mar 1998 A
5733337 Carr, Jr. et al. Mar 1998 A
5733564 Lehtinen Mar 1998 A
5736132 Juergensen et al. Apr 1998 A
5736372 Vacanti et al. Apr 1998 A
5736396 Bruder et al. Apr 1998 A
5749874 Schwartz May 1998 A
5755791 Whitson et al. May 1998 A
5759190 Vibe-Hansen et al. Jun 1998 A
5763416 Bonadio et al. Jun 1998 A
5769899 Schwartz et al. Jun 1998 A
5770229 Tanihara et al. Jun 1998 A
5770417 Vacanti et al. Jun 1998 A
5782835 Hart et al. Jul 1998 A
5782915 Stone Jul 1998 A
5786217 Tubo et al. Jul 1998 A
5788625 Plouhar et al. Aug 1998 A
5800537 Bell Sep 1998 A
5814084 Grivas et al. Sep 1998 A
5824055 Spiridigliozzi et al. Oct 1998 A
5830493 Yokota et al. Nov 1998 A
5837458 Minshull et al. Nov 1998 A
5837534 Olson et al. Nov 1998 A
5842477 Naughton et al. Dec 1998 A
5846931 Hattersley et al. Dec 1998 A
5853746 Hunziker Dec 1998 A
5855620 Bishopric et al. Jan 1999 A
5859208 Fiddes et al. Jan 1999 A
5863296 Orton Jan 1999 A
5863297 Walter et al. Jan 1999 A
5863792 Tyndorf et al. Jan 1999 A
5868415 Villeneuve Feb 1999 A
5874417 Prestwich et al. Feb 1999 A
5878444 Lai Mar 1999 A
5878452 Athanasiou et al. Mar 1999 A
5881733 Stone Mar 1999 A
5888219 Bonutti Mar 1999 A
5893888 Bell Apr 1999 A
5899936 Goldstein May 1999 A
5899939 Boyce et al. May 1999 A
5902741 Purchio et al. May 1999 A
5904716 Gendler May 1999 A
5906827 Khouri et al. May 1999 A
5908837 Cohen et al. Jun 1999 A
5908924 Burdette et al. Jun 1999 A
5910315 Stevenson et al. Jun 1999 A
5916285 Hu Jun 1999 A
5916557 Berlowitz-Tarrant et al. Jun 1999 A
5922028 Plouhar et al. Jul 1999 A
5928945 Seliktar et al. Jul 1999 A
5942496 Bonadio et al. Aug 1999 A
5948429 Bell et al. Sep 1999 A
5949252 Taguchi Sep 1999 A
5952191 Morozov Sep 1999 A
5955438 Pitaru et al. Sep 1999 A
5964805 Stone Oct 1999 A
5965125 Mineau-Hanschke Oct 1999 A
5972385 Liu et al. Oct 1999 A
5972388 McKay Oct 1999 A
5974663 Ikeda et al. Nov 1999 A
5976524 Hammerman Nov 1999 A
5989269 Vibe-Hansen et al. Nov 1999 A
5989289 Coates et al. Nov 1999 A
5989866 Deisher et al. Nov 1999 A
5998170 Arakawa et al. Dec 1999 A
6001352 Boyan et al. Dec 1999 A
6005161 Brekke et al. Dec 1999 A
6013853 Athanasiou et al. Jan 2000 A
6015711 Olson et al. Jan 2000 A
6017348 Hart et al. Jan 2000 A
6022744 Tetteroo et al. Feb 2000 A
6025334 Dupont et al. Feb 2000 A
6025538 Yaccarino, III Feb 2000 A
6027742 Lee et al. Feb 2000 A
6027743 Khouri et al. Feb 2000 A
6027744 Vacanti et al. Feb 2000 A
6030635 Gertzman et al. Feb 2000 A
6037171 Larsson Mar 2000 A
6039762 McKay Mar 2000 A
6042610 Li et al. Mar 2000 A
6056777 McDowell May 2000 A
6060640 Pauley et al. May 2000 A
6074663 Delmotte et al. Jun 2000 A
6080194 Pachence et al. Jun 2000 A
6090996 Li Jul 2000 A
6090998 Grooms et al. Jul 2000 A
6096081 Grivas et al. Aug 2000 A
6096347 Geddes et al. Aug 2000 A
6103255 Levene et al. Aug 2000 A
6110209 Stone Aug 2000 A
6110482 Khouri et al. Aug 2000 A
6110746 Cohen et al. Aug 2000 A
6118043 Nies et al. Sep 2000 A
6123731 Boyce et al. Sep 2000 A
6132472 Bonutti Oct 2000 A
6140087 Graham et al. Oct 2000 A
6143293 Weiss et al. Nov 2000 A
6146385 Torrie et al. Nov 2000 A
6150163 McPherson et al. Nov 2000 A
6156068 Walter et al. Dec 2000 A
6156572 Bellamkonda et al. Dec 2000 A
6159179 Simonson Dec 2000 A
6165487 Ashkar et al. Dec 2000 A
6171610 Vacanti et al. Jan 2001 B1
6174333 Kadiyala et al. Jan 2001 B1
6176880 Plouhar et al. Jan 2001 B1
6180605 Chen et al. Jan 2001 B1
6183737 Zaleske et al. Feb 2001 B1
6189537 Wolfinbarger, Jr. Feb 2001 B1
6193647 Beebe Feb 2001 B1
6197061 Masuda et al. Mar 2001 B1
6197586 Bhatnagar et al. Mar 2001 B1
6200347 Anderson et al. Mar 2001 B1
6201165 Grant et al. Mar 2001 B1
6214368 Lee et al. Apr 2001 B1
6221854 Radomsky Apr 2001 B1
6231607 Ben-Bassat et al. May 2001 B1
6231879 Li et al. May 2001 B1
6235316 Adkisson May 2001 B1
6242247 Rieser et al. Jun 2001 B1
6261143 Schwartz et al. Jun 2001 B1
6258778 Rodgers et al. Jul 2001 B1
6261586 McKay Jul 2001 B1
6267786 Stone Jul 2001 B1
6270528 McKay Aug 2001 B1
6274090 Coelho et al. Aug 2001 B1
6274663 Hosokawa et al. Aug 2001 B1
6274712 Springer et al. Aug 2001 B1
6280473 Lemperle et al. Aug 2001 B1
6281195 Rueger et al. Aug 2001 B1
6283980 Vibe-Hansen et al. Sep 2001 B1
6288043 Spiro et al. Sep 2001 B1
6293970 Welfinbarger, Jr. et al. Sep 2001 B1
6294187 Boyce et al. Sep 2001 B1
6294202 Burns et al. Sep 2001 B1
6294359 Fiddes et al. Sep 2001 B1
6303585 Spire et al. Oct 2001 B1
6305379 Wolfinbarger, Jr. Oct 2001 B1
6306169 Lee et al. Oct 2001 B1
6306174 Gie et al. Oct 2001 B1
6306424 Vyakarnam et al. Oct 2001 B1
6310267 Rapp Oct 2001 B1
6312725 Wallace et al. Nov 2001 B1
6315992 Noh et al. Nov 2001 B1
6319712 Meenen et al. Nov 2001 B1
6322583 Cummings et al. Nov 2001 B1
6331312 Lee et al. Dec 2001 B1
6333029 Vyakarnam et al. Dec 2001 B1
6334968 Shapiro et al. Jan 2002 B1
6337198 Levene et al. Jan 2002 B1
6346515 Pitaru et al. Feb 2002 B1
6352558 Spector Mar 2002 B1
6352971 Deisher et al. Mar 2002 B1
6361565 Bonutti Mar 2002 B1
6371958 Overaker Apr 2002 B1
6375935 Constantz Apr 2002 B1
6376244 Atala Apr 2002 B1
6378527 Hungerford et al. Apr 2002 B1
6379367 Vibe-Hansen et al. Apr 2002 B1
6379385 Kalas et al. Apr 2002 B1
6383221 Scarborough et al. May 2002 B1
6387693 Rieser et al. May 2002 B2
6398811 McKay Jun 2002 B1
6398816 Breitbart et al. Jun 2002 B1
6398972 Blasetti et al. Jun 2002 B1
6406476 Kirwan, Jr. et al. Jun 2002 B1
6417247 Armstrong et al. Jul 2002 B1
6425918 Shapiro et al. Jul 2002 B1
6432436 Gertzman et al. Aug 2002 B1
6432713 Takagi et al. Aug 2002 B2
6437018 Gertzman et al. Aug 2002 B1
6440141 Phiiippon Aug 2002 B1
6440427 Wadstrom Aug 2002 B1
6440444 Boyce et al. Aug 2002 B2
6440934 Whitehouse Aug 2002 B1
6443988 Felt et al. Sep 2002 B2
6444222 Asculai et al. Sep 2002 B1
6447701 Heschel et al. Sep 2002 B1
6451060 Masuda et al. Sep 2002 B2
6454811 Sherwood et al. Sep 2002 B1
6458144 Morris et al. Oct 2002 B1
6458158 Anderson et al. Oct 2002 B1
6458375 Gertzman et al. Oct 2002 B1
6468314 Schwartz et al. Oct 2002 B2
6475175 Rivera et al. Nov 2002 B1
6486377 Rapp Nov 2002 B2
6488033 Cerundolo Dec 2002 B1
6489165 Bhatnagar et al. Dec 2002 B2
6489455 Chenchik et al. Dec 2002 B2
6497726 Carter et al. Dec 2002 B1
6503277 Bonutti Jan 2003 B2
6504079 Tucker et al. Jan 2003 B2
6511511 Slivka et al. Jan 2003 B1
6511958 Atkinson et al. Jan 2003 B1
6514514 Atkinson et al. Feb 2003 B1
6517872 Yayon et al. Feb 2003 B1
6520964 Tallarida et al. Feb 2003 B2
6528052 Smith et al. Mar 2003 B1
6530956 Mansmann Mar 2003 B1
6533821 Lally Mar 2003 B1
6534084 Vyakarnam et al. Mar 2003 B1
6541024 Kadiyala et al. Apr 2003 B1
6548729 Seelich et al. Apr 2003 B1
6551784 Fodor et al. Apr 2003 B2
6569172 Asculai et al. May 2003 B2
6576015 Geistlich et al. Jun 2003 B2
6576265 Spievack Jun 2003 B1
6576285 Bader et al. Jun 2003 B1
6579538 Spievack Jun 2003 B1
6582960 Martin et al. Jun 2003 B1
6591581 Schmieding Jul 2003 B2
6592598 Vibe-Hansen et al. Jul 2003 B2
6592599 Vibe-Hansen et al. Jul 2003 B2
6599300 Vibe-Hansen et al. Jul 2003 B2
6599301 Vibe-Hansen et al. Jul 2003 B2
6599515 Delmotte Jul 2003 B1
6607879 Cocks et al. Aug 2003 B1
6623963 Muller et al. Sep 2003 B1
6624245 Wallace et al. Sep 2003 B2
6626950 Brown et al. Sep 2003 B2
6630000 Bonutti Oct 2003 B1
6630457 Aeschlimann et al. Oct 2003 B1
6632247 Boyer, II et al. Oct 2003 B2
6632651 Neve et al. Oct 2003 B1
6645727 Thomas et al. Nov 2003 B2
6645764 Adkisson Nov 2003 B1
6652592 Grooms et al. Nov 2003 B1
6652593 Boyer, II et al. Nov 2003 B2
6652872 Neve et al. Nov 2003 B2
6662805 Frondoza et al. Dec 2003 B2
6666892 Hiles et al. Dec 2003 B2
6673286 Shih et al. Jan 2004 B2
6686184 Anderson et al. Feb 2004 B1
6689747 Filvaroff et al. Feb 2004 B2
6696073 Boyce et al. Feb 2004 B2
6712851 Lemperle et al. Mar 2004 B1
6727224 Zhang et al. Apr 2004 B1
6730314 Jeschke et al. May 2004 B2
6734018 Wolfinbarger, Jr. et al. May 2004 B2
6737072 Angele et al. May 2004 B1
6743232 Overaker et al. Jun 2004 B2
6752834 Geistlich et al. Jun 2004 B2
6753311 Fertala et al. Jun 2004 B2
6761739 Shepard Jul 2004 B2
6761887 Kavalkovich et al. Jul 2004 B1
6764517 Yamamoto et al. Jul 2004 B2
6767369 Boyer, II et al. Jul 2004 B2
6773723 Spiro et al. Aug 2004 B1
6776800 Boyer, II et al. Aug 2004 B2
6783712 Slivka et al. Aug 2004 B2
6790454 Abdul Malak et al. Sep 2004 B1
6803234 Havenga et al. Oct 2004 B2
6808585 Boyce et al. Oct 2004 B2
6808920 Goshoo Oct 2004 B2
6815416 Carney et al. Nov 2004 B2
6838440 Stiles Jan 2005 B2
6841150 Halvorsen et al. Jan 2005 B2
6852114 Cerundolo Feb 2005 B2
6852125 Simon et al. Feb 2005 B2
6852331 Lai et al. Feb 2005 B2
6855167 Shimp et al. Feb 2005 B2
6855169 Boyer, II et al. Feb 2005 B2
6855189 Ediinger Feb 2005 B2
6858042 Nadler et al. Feb 2005 B2
6866668 Giannetti et al. Mar 2005 B2
6875442 Holy et al. Apr 2005 B2
6884428 Binette et al. Apr 2005 B2
6890354 Steiner et al. May 2005 B2
6893462 Buskirk et al. May 2005 B2
6893466 Trieu May 2005 B2
6896904 Spiro et al. May 2005 B2
6902578 Anderson et al. Jun 2005 B1
6902584 Kwan et al. Jun 2005 B2
6911212 Gertzman et al. Jun 2005 B2
6932977 Heidaran et al. Aug 2005 B2
6933326 Griffey et al. Aug 2005 B1
6939562 Spiro et al. Sep 2005 B2
6949252 Mizuno et al. Sep 2005 B2
6962814 Mitchell et al. Nov 2005 B2
6989034 Hammer et al. Jan 2006 B2
6991652 Burg Jan 2006 B2
6993328 Oommen Jan 2006 B1
6995013 Connelly et al. Feb 2006 B2
7009039 Yayon et al. Mar 2006 B2
7018416 Hanson et al. Mar 2006 B2
7022516 Kanegasaki Apr 2006 B2
7025916 Bachrach Apr 2006 B2
7033587 Halvorsen et al. Apr 2006 B2
7041641 Rueger et al. May 2006 B2
7044968 Yaccarino, III et al. May 2006 B1
7045141 Merboth et al. May 2006 B2
7048750 Vibe-Hansen et al. May 2006 B2
7048762 Sander et al. May 2006 B1
7048785 Grooms et al. May 2006 B2
7067123 Gomes et al. Jun 2006 B2
7070942 Heidaran et al. Jul 2006 B2
7078232 Konkle et al. Jul 2006 B2
7087082 Paul et al. Aug 2006 B2
7108721 Huckle et al. Sep 2006 B2
RE39321 MacPhee et al. Oct 2006 E
7115146 Boyer, II et al. Oct 2006 B2
7125423 Hazebrouck Oct 2006 B2
7125569 Nur et al. Oct 2006 B2
7132110 Kay et al. Nov 2006 B2
7137989 Asculai et al. Nov 2006 B2
7141072 Geistlich et al. Nov 2006 B2
7148209 Hoemann et al. Dec 2006 B2
7156880 Evans et al. Jan 2007 B2
7157428 Kusanagi et al. Jan 2007 B2
7163563 Schwartz et al. Jan 2007 B2
7166133 Evans et al. Jan 2007 B2
7169610 Brown Jan 2007 B2
7175852 Simmoteit et al. Feb 2007 B2
7179299 Edwards et al. Feb 2007 B2
7182781 Bianchi et al. Feb 2007 B1
7192604 Brown et al. Mar 2007 B2
7201917 Malaviya et al. Apr 2007 B2
7208177 Geistlich et al. Apr 2007 B2
7217294 Kusanagi et al. May 2007 B2
7220558 Luyten et al. May 2007 B2
7226482 Messerli et al. Jun 2007 B2
7241316 Evans et al. Jul 2007 B2
7252987 Bachalo et al. Aug 2007 B2
7264634 Schmieding Sep 2007 B2
7288406 Bogin et al. Oct 2007 B2
7291189 Hodorek Nov 2007 B2
7297181 Fell Nov 2007 B2
7299805 Bonutti Nov 2007 B2
7309232 Rutherford et al. Dec 2007 B2
7316822 Binette et al. Jan 2008 B2
7323011 Shepard et al. Jan 2008 B2
7323445 Zhang et al. Jan 2008 B2
7326571 Freyman Feb 2008 B2
7335508 Yayon et al. Feb 2008 B2
7338492 Singhatat et al. Mar 2008 B2
7338524 Fell et al. Mar 2008 B2
7358284 Griffey et al. Apr 2008 B2
7361195 Schwartz et al. Apr 2008 B2
7365051 Paulista et al. Apr 2008 B2
7371400 Barenstein et al. May 2008 B2
7452677 Lundgren-.ANG.kerlund Nov 2008 B2
7468075 Lang et al. Dec 2008 B2
7468192 Mizuno et al. Dec 2008 B2
7476257 Sah et al. Jan 2009 B2
7479160 Branch et al. Jan 2009 B2
7485310 Luyten et al. Feb 2009 B2
7488348 Truncale et al. Feb 2009 B2
7507286 Edidin et al. Mar 2009 B2
7513910 Buskirk et al. Apr 2009 B2
7524513 Hai-Quan et al. Apr 2009 B2
7531000 Hodorek May 2009 B2
7531503 Atala et al. May 2009 B2
7537617 Bindsell et al. May 2009 B2
7537780 Mizuno et al. May 2009 B2
7550007 Malinin Jun 2009 B2
7560432 Kusanagi et al. Jul 2009 B2
7563455 McKay Jul 2009 B2
7563769 Bogin et al. Jul 2009 B2
7595082 Pedrozo et al. Sep 2009 B2
7601173 Messerli et al. Oct 2009 B2
7608113 Boyer, II et al. Oct 2009 B2
7618646 Goerne et al. Nov 2009 B2
7621963 Simon et al. Nov 2009 B2
7622438 Lazarov et al. Nov 2009 B1
7622562 Thorne et al. Nov 2009 B2
7625581 Laredo et al. Dec 2009 B2
7628851 Armitage et al. Dec 2009 B2
7632311 Seedhom et al. Dec 2009 B2
7635592 West et al. Dec 2009 B2
7638486 Lazarov et al. Dec 2009 B2
7642092 Maor Jan 2010 B2
7648700 Vignery et al. Jan 2010 B2
7648985 Vignery et al. Jan 2010 B2
7658768 Miller et al. Feb 2010 B2
7662184 Edwards et al. Feb 2010 B2
7666230 Orban et al. Feb 2010 B2
7731756 Maspero et al. Jun 2010 B2
7763272 Offermann et al. Jul 2010 B2
7767806 Hirakura et al. Aug 2010 B2
7824701 Binette et al. Nov 2010 B2
7837740 Semler et al. Nov 2010 B2
7848486 Shea et al. Dec 2010 B2
7875296 Binette et al. Jan 2011 B2
7892799 Smith et al. Feb 2011 B2
RE42208 Truncale et al. Mar 2011 E
7901457 Truncale et al. Mar 2011 B2
7901461 Harmon et al. Mar 2011 B2
7931687 Masuda et al. Apr 2011 B2
8029992 Rapko et al. Oct 2011 B2
8030361 Aso et al. Oct 2011 B2
8039258 Harris et al. Oct 2011 B2
8043627 Scharnweber et al. Oct 2011 B2
8062655 Johnson et al. Nov 2011 B2
8105380 Kharazi et al. Jan 2012 B2
RE43208 Yang et al. Feb 2012 E
8110007 Borden Feb 2012 B2
8119783 Bogin et al. Feb 2012 B2
8147882 McKay Apr 2012 B2
8185485 Keith et al. May 2012 B2
8292968 Truncale et al. Oct 2012 B2
8420858 Hwang et al. Apr 2013 B2
8469980 Sengun et al. Jun 2013 B2
8507261 Ogihara et al. Aug 2013 B2
8685107 Claesson et al. Apr 2014 B2
8921109 Smith et al. Dec 2014 B2
20010005592 Bhatnagar et al. Jun 2001 A1
20010006634 Zaleske et al. Jul 2001 A1
20010010023 Schwartz et al. Jul 2001 A1
20010011131 Luyten et al. Aug 2001 A1
20010011170 Davison et al. Aug 2001 A1
20010016646 Rueger et al. Aug 2001 A1
20010018619 Enzerink et al. Aug 2001 A1
20010020188 Sander Sep 2001 A1
20010021529 Takagi Sep 2001 A1
20010021875 Enzerink et al. Sep 2001 A1
20010031254 Bianchi et al. Oct 2001 A1
20010039457 Boyer et al. Nov 2001 A1
20010039458 Boyer et al. Nov 2001 A1
20010041941 Boyer et al. Nov 2001 A1
20010043940 Boyce et al. Nov 2001 A1
20010051834 Frondoza et al. Dec 2001 A1
20010055615 Wallace et al. Dec 2001 A1
20020009805 Nevo et al. Jan 2002 A1
20020016592 Branch et al. Feb 2002 A1
20020022884 Mansmann Feb 2002 A1
20020035401 Boyce et al. Mar 2002 A1
20020042373 Carney et al. Apr 2002 A1
20020045940 Giannetti et al. Apr 2002 A1
20020055783 Tallarida et al. May 2002 A1
20020062152 Dauner et al. May 2002 A1
20020072806 Buskirk et al. Jun 2002 A1
20020082220 Hoemann et al. Jun 2002 A1
20020082623 Osther et al. Jun 2002 A1
20020082704 Cerundolo Jun 2002 A1
20020099448 Hiles et al. Jul 2002 A1
20020106393 Bianchi et al. Aug 2002 A1
20020106625 Hung et al. Aug 2002 A1
20020111695 Kandel Aug 2002 A1
20020120274 Overaker et al. Aug 2002 A1
20020138143 Grooms et al. Sep 2002 A1
20020177224 Madry et al. Nov 2002 A1
20020177859 Monassevitch et al. Nov 2002 A1
20020192283 Merboth et al. Dec 2002 A1
20030021827 Malaviya et al. Jan 2003 A1
20030023316 Brown et al. Jan 2003 A1
20030032981 Pelo et al. Feb 2003 A1
20030033021 Plouhar et al. Feb 2003 A1
20030033022 Plouhar et al. Feb 2003 A1
20030036797 Malaviya et al. Feb 2003 A1
20030036801 Schwartz et al. Feb 2003 A1
20030039695 Geistlich et al. Feb 2003 A1
20030040113 Mizuno et al. Feb 2003 A1
20030044444 Malaviya et al. Mar 2003 A1
20030049299 Malaviya et al. Mar 2003 A1
20030050709 Noth et al. Mar 2003 A1
20030055502 Lang et al. Mar 2003 A1
20030078617 Schwartz et al. Apr 2003 A1
20030095993 Bentz et al. May 2003 A1
20030099620 Zaleske et al. May 2003 A1
20030144743 Edwards et al. Jul 2003 A1
20030198628 Hammerman Oct 2003 A1
20030225355 Butler Dec 2003 A1
20030229400 Masuda et al. Dec 2003 A1
20030236573 Evans et al. Dec 2003 A1
20040028717 Sittinger et al. Feb 2004 A1
20040033212 Thomson et al. Feb 2004 A1
20040039447 Simon et al. Feb 2004 A1
20040044408 Hungerford et al. Mar 2004 A1
20040062753 Rezania et al. Apr 2004 A1
20040078090 Binette et al. Apr 2004 A1
20040082084 Reisner et al. Apr 2004 A1
20040102850 Shepard May 2004 A1
20040107003 Boyer et al. Jun 2004 A1
20040115172 Bianchi et al. Jun 2004 A1
20040134502 Mizuno et al. Jul 2004 A1
20040138748 Boyer et al. Jul 2004 A1
20040143344 Malaviya et al. Jul 2004 A1
20040151705 Mizuno et al. Aug 2004 A1
20040166169 Malaviya et al. Aug 2004 A1
20040170610 Slavin et al. Sep 2004 A1
20040175826 Maor Sep 2004 A1
20040192605 Zhang et al. Sep 2004 A1
20040193154 Leatherbury et al. Sep 2004 A1
20040193208 Hazebrouck Sep 2004 A1
20040197307 Rezania et al. Oct 2004 A1
20040197311 Brekke et al. Oct 2004 A1
20040197373 Gertzman et al. Oct 2004 A1
20040197375 Rezania et al. Oct 2004 A1
20040214313 Zhang Oct 2004 A1
20040219182 Gomes et al. Nov 2004 A1
20040220574 Pelo et al. Nov 2004 A1
20040230303 Gomes et al. Nov 2004 A1
20040234549 Chiang et al. Nov 2004 A1
20040243242 Sybert et al. Dec 2004 A1
20040267277 Zannis et al. Dec 2004 A1
20050004672 Pafford et al. Jan 2005 A1
20050027307 Schwartz et al. Feb 2005 A1
20050038520 Binette et al. Feb 2005 A1
20050042254 Freyman et al. Feb 2005 A1
20050043814 Kusanagi et al. Feb 2005 A1
20050064042 Vunjak-Novakovic et al. Mar 2005 A1
20050074476 Gendler et al. Apr 2005 A1
20050074481 Brekke et al. Apr 2005 A1
20050089544 Khouri et al. Apr 2005 A1
20050101957 Buskirk et al. May 2005 A1
20050112761 Halvorsen et al. May 2005 A1
20050125077 Harmon et al. Jun 2005 A1
20050129668 Giannetti et al. Jun 2005 A1
20050152882 Kizer et al. Jul 2005 A1
20050159820 Yoshikawa et al. Jul 2005 A1
20050159822 Griffey et al. Jul 2005 A1
20050161857 Coombes et al. Jul 2005 A1
20050191248 Hunter et al. Sep 2005 A1
20050196480 Malinin Sep 2005 A1
20050209705 Niederauer et al. Sep 2005 A1
20050222687 Vunjak-Novakovic et al. Oct 2005 A1
20050228498 Andres Oct 2005 A1
20050240281 Slivka et al. Oct 2005 A1
20050251288 Truncate Nov 2005 A1
20050255458 Polansky Nov 2005 A1
20050260612 Padmini et al. Nov 2005 A1
20050261681 Branch et al. Nov 2005 A9
20050261767 Anderson et al. Nov 2005 A1
20050288796 Awad et al. Dec 2005 A1
20060030948 Manrique et al. Feb 2006 A1
20060060209 Shepard Mar 2006 A1
20060099234 Winkler May 2006 A1
20060105015 Perla et al. May 2006 A1
20060111778 Michalow May 2006 A1
20060141607 Wikswo Jun 2006 A1
20060167483 Asculai et al. Jul 2006 A1
20060178748 Dinger et al. Aug 2006 A1
20060200186 Hanson et al. Sep 2006 A1
20060204445 Atala et al. Sep 2006 A1
20060210643 Truncale et al. Sep 2006 A1
20060216323 Knaack et al. Sep 2006 A1
20060216822 Mizuno et al. Sep 2006 A1
20060235534 Gertzman et al. Oct 2006 A1
20060247790 McKay Nov 2006 A1
20060247791 McKay et al. Nov 2006 A1
20060251631 Adkisson et al. Nov 2006 A1
20060276907 Boyer et al. Dec 2006 A1
20060286144 Yang et al. Dec 2006 A1
20070009610 Syring Jan 2007 A1
20070014867 Kusanagi et al. Jan 2007 A1
20070026030 Gill et al. Feb 2007 A1
20070036834 Pauletti et al. Feb 2007 A1
20070041950 Leatherbury et al. Feb 2007 A1
20070043376 Leatherbury et al. Feb 2007 A1
20070055377 Hanson et al. Mar 2007 A1
20070057175 Mordehai et al. Mar 2007 A1
20070065943 Smith et al. Mar 2007 A1
20070067032 Felt et al. Mar 2007 A1
20070083266 Lang Apr 2007 A1
20070093896 Malinin Apr 2007 A1
20070093912 Borden Apr 2007 A1
20070098759 Malinin May 2007 A1
20070100450 Hodorek May 2007 A1
20070113951 Huang May 2007 A1
20070128155 Seyedin et al. Jun 2007 A1
20070134291 Ting et al. Jun 2007 A1
20070135917 Malinin Jun 2007 A1
20070135918 Malinin Jun 2007 A1
20070135928 Malinin Jun 2007 A1
20070148242 Vilei et al. Jun 2007 A1
20070162121 Tarrant et al. Jul 2007 A1
20070168030 Edwards et al. Jul 2007 A1
20070172506 Nycz et al. Jul 2007 A1
20070178159 Chen et al. Aug 2007 A1
20070179607 Hodorek et al. Aug 2007 A1
20070185585 Bracy et al. Aug 2007 A1
20070190030 Pawliuk et al. Aug 2007 A1
20070202190 Borden Aug 2007 A1
20070219497 Johnson et al. Sep 2007 A1
20070276506 Troxel Nov 2007 A1
20070299517 Davisson et al. Dec 2007 A1
20070299519 Schmieding Dec 2007 A1
20080015709 Evans et al. Jan 2008 A1
20080027546 Semler et al. Jan 2008 A1
20080031915 Becerra Ratia et al. Feb 2008 A1
20080038314 Hunziker Feb 2008 A1
20080039939 Iwamoto et al. Feb 2008 A1
20080039954 Long Feb 2008 A1
20080039955 Hunziker Feb 2008 A1
20080051889 Hodorek Feb 2008 A1
20080055210 McKay Mar 2008 A1
20080064090 Whittlinger Mar 2008 A1
20080077251 Chen et al. Mar 2008 A1
20080119947 Huckle et al. May 2008 A1
20080125883 McKay May 2008 A1
20080125888 Branemark et al. May 2008 A1
20080133008 Truncale et al. Jun 2008 A1
20080138414 Huckle et al. Jun 2008 A1
20080153157 Yao et al. Jun 2008 A1
20080154372 Peckham Jun 2008 A1
20080166329 Sung et al. Jul 2008 A1
20080167716 Schwartz et al. Jul 2008 A1
20080183300 Seedhom et al. Jul 2008 A1
20080220044 Semler et al. Sep 2008 A1
20080255676 Semler et al. Oct 2008 A1
20080260801 Ahlers et al. Oct 2008 A1
20080274157 Vunjak-Novakovic et al. Nov 2008 A1
20080287342 Yu et al. Nov 2008 A1
20080305145 Shelby et al. Dec 2008 A1
20080306408 Lo Dec 2008 A1
20090001267 Enyama et al. Jan 2009 A1
20090043389 Vunjak-Novakovic et al. Feb 2009 A1
20090069901 Truncale et al. Mar 2009 A1
20090069904 Picha Mar 2009 A1
20090076624 Rahaman et al. Mar 2009 A1
20090099661 Bhattacharya et al. Apr 2009 A1
20090112119 Kim Apr 2009 A1
20090117652 Luyten et al. May 2009 A1
20090131986 Lee et al. May 2009 A1
20090139045 Cannon et al. Jun 2009 A1
20090143867 Gage et al. Jun 2009 A1
20090148941 Florez et al. Jun 2009 A1
20090149893 Semler et al. Jun 2009 A1
20090210057 Liao et al. Aug 2009 A1
20090226523 Behnam et al. Sep 2009 A1
20090280179 Neumann et al. Nov 2009 A1
20090291112 Truncale et al. Nov 2009 A1
20090299475 Yamamoto et al. Dec 2009 A1
20090312805 Lang et al. Dec 2009 A1
20090312842 Bursac et al. Dec 2009 A1
20090319051 Nycz et al. Dec 2009 A9
20100015202 Semler et al. Jan 2010 A1
20100021521 Xu et al. Jan 2010 A1
20100036492 Hung et al. Feb 2010 A1
20100036503 Chen et al. Feb 2010 A1
20100241228 Syring et al. Sep 2010 A1
20100274362 Yayon et al. Oct 2010 A1
20100291181 Uhrich et al. Nov 2010 A1
20110053841 Yayon et al. Mar 2011 A1
20110070271 Truncale et al. Mar 2011 A1
20110196508 Truncale et al. Aug 2011 A1
20110224797 Semler et al. Sep 2011 A1
20110282372 Schowalter et al. Nov 2011 A1
20130273121 Mizuno et al. Oct 2013 A1
Foreign Referenced Citations (117)
Number Date Country
0068149 Jan 1983 EP
0075444 Mar 1983 EP
0337677 Oct 1989 EP
0517030 Dec 1992 EP
0522569 Jan 1993 EP
0608546 Aug 1994 EP
0620274 Oct 1994 EP
0674908 Oct 1995 EP
0677297 Oct 1995 EP
0739631 Oct 1996 EP
0784985 Jul 1997 EP
1127581 Aug 2001 EP
1181908 Feb 2002 EP
1208850 May 2002 EP
1234552 Aug 2002 EP
1234555 Aug 2002 EP
1264607 Dec 2002 EP
1384452 Jan 2004 EP
1452191 Sep 2004 EP
1537883 Jun 2005 EP
1561481 Aug 2005 EP
1625832 Feb 2006 EP
1719463 Nov 2006 EP
1719531 Nov 2006 EP
1719532 Nov 2006 EP
1923457 May 2008 EP
2657352 Jul 1991 FR
2102811 Feb 1983 GB
622744 Feb 1994 JP
9001342 Feb 1990 WO
9011354 Oct 1990 WO
9101140 Feb 1991 WO
9109126 Jun 1991 WO
9304169 Mar 1993 WO
9316739 Sep 1993 WO
9320218 Oct 1993 WO
9403584 Feb 1994 WO
9429442 Dec 1994 WO
9525748 Sep 1995 WO
9533502 Dec 1995 WO
9601313 Jan 1996 WO
9603159 Feb 1996 WO
9615818 May 1996 WO
9624310 Aug 1996 WO
9640892 Dec 1996 WO
9707668 Mar 1997 WO
9707669 Mar 1997 WO
9729715 Aug 1997 WO
9740163 Oct 1997 WO
9814222 Apr 1998 WO
9841246 Sep 1998 WO
9843686 Oct 1998 WO
9844874 Oct 1998 WO
9909914 Mar 1999 WO
9911298 Mar 1999 WO
9915209 Apr 1999 WO
9921497 May 1999 WO
9922747 May 1999 WO
9948541 Sep 1999 WO
9952572 Oct 1999 WO
9956797 Nov 1999 WO
00040177 Jul 2000 WO
0044808 Aug 2000 WO
00047114 Aug 2000 WO
0047214 Aug 2000 WO
0102030 Jan 2001 WO
0107595 Feb 2001 WO
0138357 May 2001 WO
0139788 Jun 2001 WO
0143667 Jun 2001 WO
0146418 Jun 2001 WO
02018546 Mar 2002 WO
0222779 Mar 2002 WO
0236732 May 2002 WO
0241877 May 2002 WO
02058484 Aug 2002 WO
02064180 Aug 2002 WO
02077199 Oct 2002 WO
02095019 Nov 2002 WO
03007805 Jan 2003 WO
03007873 Jan 2003 WO
03007879 Jan 2003 WO
03012053 Feb 2003 WO
03035851 May 2003 WO
03040113 May 2003 WO
03049626 Jun 2003 WO
03079885 Oct 2003 WO
03087160 Oct 2003 WO
03094835 Nov 2003 WO
2004016276 Feb 2004 WO
2004060404 Jul 2004 WO
2004067704 Aug 2004 WO
2004069298 Aug 2004 WO
2004075940 Sep 2004 WO
2004096983 Nov 2004 WO
2004103224 Dec 2004 WO
2005023321 Mar 2005 WO
2005023906 Mar 2005 WO
2005058207 Jun 2005 WO
2005110278 Nov 2005 WO
2006001046 Jan 2006 WO
2006038287 Apr 2006 WO
2006042311 Apr 2006 WO
2006050213 May 2006 WO
2006113586 Oct 2006 WO
2007024238 Mar 2007 WO
2007035778 Mar 2007 WO
2007057175 May 2007 WO
2008013763 Jan 2008 WO
2008021127 Feb 2008 WO
2008038287 Apr 2008 WO
2008081463 Jul 2008 WO
2008106254 Sep 2008 WO
2009076164 Jun 2009 WO
2009111069 Sep 2009 WO
2010083051 Jul 2010 WO
2013043072 Mar 2013 WO
Non-Patent Literature Citations (404)
Entry
European Search Opinion and Extended European Search Report in Application No. 15865074.7, dated Jun. 22, 2018.
OsteoSponge product information, Bacterin International Inc, May 2005.
Skolnick, J. et al., “From genes to protein structure and function: novel application of computational approaches in the genomic era” Trends BioTechnol., 2000, 18(1):34-39.
Doerks, T. et al., “Protein annotation: detectivework for protein prediction” Trends Genet., 1998, 14(6): 248-250.
Cook, J.L. et al., “Biocompatibility of three-dimensional chondrocyte grafts in large tibial defects of rabbits”, Am J. Vet. Res., 2003, 64(1):12-20.
International Search Report and Written Opinion of the International Searching Authority dated Mar. 14, 2016 for International Application No. PCT/US2015/063161 (17 Pages).
Office Action dated Apr. 19, 2007 in connection with U.S. Appl. No. 11/151,270.
Office Action dated Aug. 19, 2009 In connection with U.S. Appl. No. 12/147,042.
Office Action dated Dec. 18, 2007 In connection with U.S. Appl. No. 11/081,103.
Office Action dated Feb. 20, 2007 tn connection with U.S. Appl. No. 10/960,960.
Office Action dated Feb. 6, 2007 in connection with U.S. Appl. No. 10/438,883.
Office Action dated Feb. 7, 2008 in connection with U.S. Appl. No. 10/815,778.
Office Action dated Jan. 14, 2010 in connection with U.S. Appl. No. 11/081,103.
Office Action dated Jul. 2, 2009 in connection with U.S. Appl. No. 10/815,778.
Office Action dated Jul. 22, 2009 in connection with U.S. Appl. No. 12/010,984.
Office Action dated Jul. 9, 2008 in connection with U.S. Appl. No. 11/151,270.
Office Action dated Jun. 3, 2009 in connection with U.S. Appl. No. 11/081,103.
Office Action dated Jun. 8, 2009 in connection with U.S. Appl. No. 11/481,955.
Office Action dated May 18, 2009 in connection with U.S. Appl. No. 11/657,042.
Office Action dated May 3, 2005 in connection with U.S. Appl. No. 10/438,883.
Office Action dated Nov. 12, 2008 in connection with U.S. Appl. No. 10/438,883.
Office Action dated Nov. 5, 2004 in connection with U.S. Appl. No. 10/438,883.
Office Action dated Oct. 5, 2005 in connection with U.S. Appl. No. 10/424,765.
Corpet, 1988, Multiple sequence alignment with hierarchical clustering, Nucleic Acids Res, 16(22):10881-90.
Coughlin et al., 1988, Acidic and Basic Fibroblast Growth Factors Stimulate Tyrosine Kinase Activity in Vivo, Journal of Biological Chemistry, 263(2):986-993.
Coulson et al., 1999, Collagen and a thermally reversible poloxamer deliver demineralized bone matrix (DBM) and biologically active proteins to sites of bone regeneration in: Portland Sons Symposium, Jeffrey O Hollinger: Proceedings from Portland Bone Symposium, Oregon Health Sciences University, US, 619-637.
Crameri et al., 1997, Molecular evolution of an arsenate detoxification pathway by DNA shuffling. Nature Biotech, 15:436-438.
Cuenco et, al., 2001, Cooperation of BCR-ABL and AML1/MDSU/EVI1 in blocking myeloid differentiation and rapid induction of an acute myelogenous leukemia, Oncogene, 20:8238-8248.
Dahlberg et, al., 1991, Demineralized Allogeneic Bone Matrix for Cartilage Repair, Journal of Orthopaedic Research, 9:11-19.
Danilenko et al., 1999, Recombinant rat fibroblast growth factor-16: structure and biological activity, Arch. Biochem. Blophys, 361:34-46.
De Jagereta et al., 2003, Simultaneous detection of 15 human cytokines in a singie sample of stimulated peripheral blood mononuclear cells, Clin & Diagn Lab Immunol, 10:133-139.
DeKoter et. al., 1998, EMBO 17:4456-4468.
Delezoide et. al., 1998, Spatio-temporal expression of FGFR 1, 2 and 3 genes during human embryo-fetal ossification, Mech Dev 77(1):19-30.
Dell'Accio et. al., 2001, Molecular markers predictive of the capacity of expanded human articular chondrocytes to form stable cartilage in vivo, Arthritis Rheum, 44(7):1608-19.
Dellow, et. al., 2001, Cardiovasc Res 50:3-6.
Deng et. al., 1996, Fibroblast Growth Factor Receptor 3 Is a Negative Regulator of Bone Growth, Cell 84:911-921.
Denissen et. al., 1994, Bone Miner, 25:123-134.
Denissen, et. al., 2009, J Periodontol, 71:279-86.
Diduch et. al., 2002, Joint Repair: Treatment Options far Articular Cartilage Injury Orthopedic Technology Review, 4:24-27.
Dinser et. al., 2001, Comparison of long-term transgene expression after non-viral and adenoviral gene transfer into primary articuiar chondrocytes, Histochem Cell Biol, 116(1):69-77.
Dionne et. al., 1990, Cloning and expression of two distinct high-affinity receptors cross-reacting with acidic and basic fibroblast growth factors, The EMBO Joumal, 9(9):2685-2692.
Dreyfus et. al., 1995, Expression of the Evi-1 gene in myelodysplastic syndromes, Leukemia, 9:203-205.
Dvorakova et. al., 2001, Changes In The Expression Of FGFR3 In Patients With Chronic Myeloid Leukaemia Receiving Transplants Of Allogeneic Peripheral Blood Stem Cells, British Journal of Haematology, 113:832-835.
Eliopoulos et. al., 2002, Human cytidine deaminase as an ex vivo drug selectable marker in gene-modified primary bone marrow stromal cells, Gene Ther, 9:452-462.
Elroy-Stein et. al., 1989, Cap-independent translation of mRNA conferred by encephalomyocarditis virus 5' sequence improves the performance of the vaccinia virus/bacterophage T7 hybrid expression system, Proc. Natl. Acad. Sci., 86:6126-6130.
EP App No. 2004/0781499, Third party observation, mailed Jul. 30, 2014.
Eriksson et. al., 1991, Three-Dimensional structure of human basic fibroblast growth factor Proceedings of the National Academy of Science of USA, National Academy of Science, Washington, DC, US, 88:3441-3445.
Eriebacher et. al., 1995, Toward a Molecular Understanding of Skeletal Development, Cell, 80:371-378.
European Search Report and Opinion for EP1119081.17 dated Feb. 14, 2012, 10 pages.
Evans et. al., 2004, Osteoarthritis gene therapy Gene Ther, 11(4):379-89.
Extended European Search Report for European Patent Application No. 06814983.0, dated Apr. 19, 2012, 7 pages.
Ezzat et. al., 2002, Targeted Expression of a Human Pituitary Tumor-Derived Isoform of FGF Receptor-4 Recapitulates Pituitary Tumorigenesis, The Journal of Clinical Investigation, 109:69-78.
F Lincoln Avery, Anterior Cruciate Ligament (ACL) Graft Options, hitp://wwworthoassociatescom/ACL_graftshtm, Internet Article, The Sports Medicine Center, 1-15, Downloaded Jan. 9, 2007.
Feham et. al., 1998, Diversity Does Make a Difference: Fibroblast Growth Factor-Heparin Interactions, Current Opinion in Structural Biology, 8:578-586.
Feller et. al., 1984, Liposome encapsulation of retrovirus allows efficient superinfection of resistant cell lines, J Virol, 49(1):269-272.
Zhang et. al., 2004, Hyaline cartilage engineered by chondrocytes in pellet culture, histological., immunohistochemical and ultrastructural analysis in comparison with cartilage explants, J. Anat., 205(3):229-37.
Zhu et. al., 1995, GLU-96 of Basic Fibroblast Growth Factor Is Essential for High Affinity Receptor Binding Journal of Biological Chemistry, American, Society of Biochemical Biologists, Birmingham US, 270(37):21869-21874.
Zhu et. al., 1997, Analysis of high-affinity binding determinants in the receptor binding epitope of basic fibroblast growth factor, Protein Engineering, 10:417-421.
Messner et. al., 1996, The Long-term Prognosis for Severe Damage to Weight-bearing Cartilage in the Knee: A 14-year Clinical and Radiographic Follow-up in 28 Young Athletes, Acta Orthopaedica Scandinavica, 67(2):165-168.
Mitani et. al., 1994, Generation of the AML1-EVI-1 fusion gene in the t(3;21)(q26;q22) causes blastic crisis in chronic myelocytic leukemia, EMBO J., 13(3):504-510.
Miyamoto et al., 1993, Molecular Cloning of Novel Cytokine cDNA Encoding the Ninth Member of the Fibroblast Growth Factor Family, Which Has a Unique Secretion Property, Molecular and Cellular Biology, 13:4251-4259.
Miyazaki, 2002, Random DNA fragmentation with endonuclease V: application to DNA shuffling, Nucleic Acids Research, 30(24):E139.
Mohammadi et. al., 2005, Structural Basis for Fibroblast Growth Factor Receptor Activation, Cytokine & Growth Factor Rev., 16:107-137.
Morishita et. al., 1992, Activation of the EVI1 gene expression in human acute myelogenous leukemias by translocations spanning 300-400 kilobases on chromosome 3q26, Proc. Natl. Acad. Sci. USA, 89:3937-3941.
Morishita et. al., 1992, Expression of the Evi-1 zinc finger gene in 32Dc13 myeloid cells blocks granulocytic differentiation in response to granulocyte colony-stimulating factor, Mol Cell Biol., 12:183-189.
Mucenski et. al., 1988, Identification of a Common Ecotropic Viral Integration Site, Evi-1, iii the DNA of AKXD Murine Myeloid Tumors, Molecular and Cellular Biology, 8:301-308.
Nakatake et. al., 2001, Identification of a Novel Fibroblast Growth Factor, FGF-22, Preferentially Expressed in the Inner Root Sheath of the Hair Follicle, Biochimica et. Biophysics Acta, 1517:460-463.
Naruo et. al., 1993, Novel Secretory Heparin-binding Factors from Human Glioma Cells (Glia-activating Factors) Involved in Glial Cell Growth, The Journal of Biological Chemistry, 268(4):2857-2884.
Needleman et. al., 1970, A General Method Applicable to the Search for Similarities in the Amino Acid Sequence of Two Proteins, J. Mol. Biol., 48:443-453.
Nehrer et. al., 1998, Chondrocyte-seeded Collagen Matrices Implanted in a Chondral Defect in a Canine Model, Biomaterials, 19:2313-2328.
Nettles et. al., 2004, in Situ Crosslinkable Hyaluranan for Articular Cartilage Repair, 50th Annual Meeting of the Orthopaedic Research Society, Paper No. 0202.
Nettles et. al., 2004, Photocrosslinkable Hyaluronan as a Scaffold for Articular Cartilage Repair, Annals of Biomedical Engineering, 32(3):391-397.
Neville-Webbe et al., 2002, The anti-tumour activity of bisphosphonates, Cancer Treatement Reviews 28(6):305-319.
Newman, 1998. Articular Cartilage Repair, American Journal of Sports Medicine, 26(2):309-324.
Ngo et. al., 1994, Computational complexity, protein structure prediction, and the Levirithal Paradox, In: The Protein Folding Problem and Tertiary Structure Prediction K Merz Jr and S Le Grand, Editors:433-506.
Nishimura et. al., 2000, Identification of a Novel FGF, FGF-21, Preferentially Expressed in the Liver, Biochimica et. Biophysica Acta, 1492:203-206.
Nixon et. al., 1999, Enhanced Repair of Extensive Articular Defects by Insulin-like Growth Factor-I-Laden Fibrin Composites, Journal of Orthopaedic Research, 17(4):475-487.
Non-final Office Action for U.S. Appl. No. 12/043,001, dated May 11, 2011.
Non-final Offce Action with regard to U.S. Appl. No. 12/381,072, dated Jan. 20, 2011.
O'Gorman et. al., 1991, Recombinase-mediated gene activation and site-specific integration in mammalian cells, Science, 251:1351-1355.
Obradovic et. al., 2001, Integration of Engineered Cartilage, Journal of Orthopaedic Research, 19:1089-1097.
Ochi et. al., 2001, Current Concepts in Tissue Engineering Technique for Repair of Cartilage Defect, Artificial Organs, 25(3):172-179.
Office Action for Canadian Patent Application No. 2,623,106, dated Jul. 10, 2012, 3 pages.
Office Action for Canadian Patent Application No. 2,623,106, dated Oct. 6, 2011, 4 pages.
Oh et. al., 2003, Signaling Mechanisms Leading to the Regulation of Differentiation and Apoptosis of Articular Chondrocytes by Insulin-like Growth Factor-1, Journal of Biological Chemistry, 278(38):36563-36571.
Okada-Ban et. al., 2000, Molecules in focus, Fibroblast Growth Factor-2, The International Journal of Biochemistry & Cell Biology, 32:263-267.
Olsen et. al., 2003, Fibroblast Growth Factor (FGF) Homologous Factors Share Structural but not Functional Homology with FGFs, J. Biol. Chem., 278(38):34226-34236.
Olsen et. al., 2004, Insights into the Molecular Basis for Fibroblast Growth Factor Receptor Autoinhibition and Ligand- Binding Promiscuity, Proc. Nati. Acad. Sci., 101:935-940.
Ornitz et. al., 1992, Ligand Specificity and Heparin Dependence of Fibroblast Growth Factor Receptors 1 and 3, The Journal of Biological Chemistry, 267(23):16305-16311.
Ornitz et. al., 1996, Receptor Specificity of the Fibroblast Growth Factor Family*, The Journal of Biological Chemistry, 271(25):15292-15297.
Ornitz et. al., 2001, Protein Family Review, Fibroblast Growth Factors Genome Biology, 2(3):30051-300512.
Ornitz, 2000, FGFs, heparan sulfate and FGFRs: complex interactions essential for development, Bioessays, 22(2):108-112.
Patent Examination Report No. 1 for Australian Patent Application No. 2006292224, dated Oct. 4, 2011, 3 pages.
Patent Examination Report No. 2 for Australian Patent Application No. 2006292224, dated Jul. 3, 2013, 4 pages.
Pearson et. al., 1988, Improved tools for biological sequence comparison, Proc. Natl. Acad. Sci. USA, 85(8):2444-2448.
Pei et. al., 2002, Bioreactors Mediate the Effectiveness of Tissue Engineering Scaffolds, The FASEB Journal., 16:1691-1694.
Pei et. al., 2002, Growth Factors for Sequential Cellular De- and Re-differentiation in Tissue Engineering, Biochemical and Biophysical Research Communications, 294:149-154.
Pellegrini et. al., 2000, Crystal Structure of Fibroblast Growth Factor Receptor Ectodomain Bound to Ligand and Heparin, Nature, 407:1029-1034.
Pereboeva et. al., 2003, Approaches to Utilize Mesenchymal Progenitor Cells as Cellular Vehicles, Stem Cells, 21:389-404.
Peretti et. al., 1998, Bonding of Cartilage Matrices with Cultured Chondrocytes: An Experiential Model, Journal of Orthopedic Research, 16(1):89-95.
Peretti et. al., 1999, Biomechanical Analysis of a Chondrocyte-Based Repair Model of Articular Cartilage, Tissue Engineering, 5(4):317-326.
Peretti et. al., 20130, Cell-based Tissue-Engineered Allogeneic Implant for Cartilage Repair, Tissue Engineering, 6(5):567-576.
Peretti et. al., 2001, A Biomedical Analysis of an Engineered Cell-Scaffold Implant for Cartilage Repair, Annals of Plastic Surgery, 46(5):533-537.
Peretti et. al., 2003, Cell-Based Bonding of Articular Cartilage: An Extended Study, Journal of Biomedical Materials Research, 64A:517-524.
Peretti et. al., 2007, In Vitro Bonding of Pre-seeded Chondrocyte, Sport Sciences for Health 2(1):29-33.
Peterson et. al., 2000, Two- to 9-year Outcome After Autologous Chondrocyte Transplantation of the Knee, Clinical Orthopaedics and Related Research, 374:212-234.
Peterson et. al., 2002, Autologous Chondrocyte Transplantation: Biomechanics and Long-term Durability, American Journal of Sports Medicine, 30(1):2-12.
Phillips, 2001, The challenge of gene therapy and DNA delivery, Journal of Pharmacy and Pharmacology, 53:1169/1174.
Piliai et. al., 2001, Polymers In Drug Delivery, Current Opinion Chemical Biology, 5:447-451.
Plotnikov et. al., 1999, Structural Basis for FGF Receptor Dimerization and Activation, Cell, 98:641-650.
Plotnikov et. al., 2000, Crystal Structures of Two FGF-FGFR Complexes Reveal the Deteminants of Ligand-Receptor Specificity, Cell 101:413-424.
Pollik et. al., 1995; J Oral Maxillofac Surg, 53(8):915-22.
Pouyani et. al., 1994, Functionalized Derivatives of Hyaluronic Acid Oligosaccharides: Drug Carriers and Novel Biomaterials, Bioconjugate Chem., 5:339-347.
Presta et. al., 1993, Subcellular Localization and Biological Activity of Mr 18,000 Basic Fibroblast Growth Factor: Site-Directed Mutagenesis of a Putative Nuclear Translocation Sequence, Growth Factors, 9:269-278.
Prestwich et. al., 1998, Controlled chemical modification of hyaluronic acid: synthesis, applications, and biodegradation of hydrazide derivatives, Journal of Controlled Release, 53:93-103.
Rabie et. al., 1996, Ultrastructural identification ofcells involved in the healing of intramembranous and endochondral bones, Int J Oral Maxillofac Surg, 25(5):383-388.
Raisz, 1999, Physiology and Pathophysiology of Bone Remodeling, Clinical Chemistry, 45(8):1353-1358.
Richardson et. al., 1999, Repair of human articular cartilage after implantation of autologous chondrocytes, Journal of Bone and Joint Surgery [Br], 81-B:1064-1068.
Riggs et. al., 1987, Luciferase reporter gene cassettes for plant gene xpression studies, Nucleic Acid Res 15(19):8115.
Sahni et. al., 1999, FGF signalin inhibits chondrocyte proliferation and regulates bone development through the STAT-1 pathway Genes Dev., 13(11):1361-1386.
Santos-Ocampo et. al., 1996, Expression and Biological Activity of Mouse Fibroblast Growth Factor-9:, The Journal of Biological Chemistry, 271:1726-1731.
Schaefer et. al., 2002, Tissue Engineered Composites for the Repair of Large Osteochondral Defects, Arthritis & Rheumatism, 46(9):2524-2534.
Schlessinger et. al., 2000, Crystal Structure of a Ternary FGF-FGFR-Heparin Complex Reveals a Dual Role for Heparin in FGFR Binding and Dimerization, Molecular Cell, 6:743-750.
Schmal et. al., 2007, bFGF influences human articular chondrocyte differentiation, Cytotherapy, 9(2):184-193.
Schwartz et. al., 1991, A dominant positive and negative selectable gene for use mammalian cells, Proc. Natl. Acad. Sci. USA, 88(23):10416-20.
Schwarz et. al., 2000, Quantitative small-animal surrogate to evaluate drug efficacy in preventing wear debris-induced osteolysis, J Orthop Res, 18:849-55.
Schwindt et. al., 2009, Effects of FGF-2 and EGF removal on the differentiation of mouse neural precursor cells, An Acad Bras Cienc, 81(3):443-452.
Search Report Application No. PCT/IL2004/000088 dated Aug. 18, 2004.
Search Report conducted by the Australian Patent Office dated Mar. 14, 2008 regarding Singapore Patent Application No. 200607828-1.
Search Report conducted by the Danish Patent Office dated Jul. 15, 2005 regarding Singapore Patent Application No. 200406581-9.
Search Report for PCT/IL2007/001199, dated Sep. 16, 2008.
Search Report for PCT/US2008/073762 dated Dec. 22, 2008.
Search Report, PCT/IL07/01199, dated Sep. 16, 2008.
Seddon et. al., 1995, Engineering of Fibroblast Growth Factor Alteration of Receptor Binding Specificity, Biochemistry, 34:741-736.
Shaklee et. al., 1984, Hydrazinolysis of heparin and other glycosaminoglycans, Biochem. J., 217:187-197.
Sheo et. al., 2006, Effects of intramyocardial administration of slow-release basic fibroblast growth factor on angiogenesis and ventricular remodeling in a rat infarct model, Circ J, 70(4):471-477.
Shibata et. al., 2001, GM-CSF Regulates Alveolar Macrophage Differentiation and Innate Immunity in the Lung through PU.1, Immunity, 15(4):557-567.
Shu et. al, 2003, Attachment and spreading fibroblasts on an RGD peptide-modified injectable hyaluronan hydrogel, Wiley periodicals.
Shu et. al., 2004, Attachment and spreading of fibroblasts on an RGD peptide-modified injectable hyaluronan hydrogel, J Biomed, Mater Res 68A:365-375.
Sims et. al., 1998, Tissue Engineered Neocartilage Using Plasma Derived Polymer Substrates and Chondrocytes, Plastic & Recon Surg 101(6):1580-1585.
Skolnick et. al., 2000, From genes to protein structure and function: novel applications of computationai approaches in the genomic era, Trends BioTechnol, 18(1):34-39.
Sleeman et. al., 2001, Identification of a new fibrobiast growth factor receptor, FGFR5, Gene, 271(2): 171-182.
Smith et, al., 1996, In vitro stimulation of articular chondrocyte mRNA and extracellular matrix synthesis by hydrostatic pressure, Journal of Orthopaedic Research, John Wiley & Sons, Inc, 14(1):53-60.
Smith et. al., 1997, The challenges of genome sequence annotation or 'The devilis in the details, Nature Biotechnology, 15(12):1222-1223.
Soltes et al., 2003, Molecular characterization of two host-guest associating hyaluronan derivatives, Biomedical Chromatography, 17;376-384.
Song et. al., 2002, Construction of DNA-Shuffled and Incrementally Truncated Libraries by a Mutagenic and Unidirectional Reassembly Method: Changing from a Substrate Specificity of Phospholipase to That of Lipase, Appl. Environ. Microbiol., 68(12):6146-6151.
Spangenberg et. al., 2002, Histomorphometric Analysis of a Cell-Based Model of Cartilage Repair, Tissue Engineering, 8(5):839-46.
Springer et. al, 1994, Identification and Concerted Function of Two Receptor:Binding Surfaces on Basic Fibroblast Growth Factor Required for Mitogenesis, The Journal of Biological Chemistry, 269(43):26879-26884.
Stauber et. al., 2000, Structural interactions of fibroblast growth factor receptor with its ligands, PNAS, 97(1):49-54.
Stemmer et. al., 1994, DNA shuffling by random fragmentation and reassembly; in vitro recombination for molecular evolution, Proc. Natl. Acad. Sci, USA, 91(22):10747-10751.
Stone et. al., 2006, Articular Cartilage Paste Grafting to Full-Thickness Articular Cartilage Knee Joint Lesions: A 2- 12-Year Follow-up, Arthroscopy: The Journal of Arthroscopic and Related Surgery, 22(3):291-299.
Stone et. al., One-Step American Technique of Articular Cartilage Paste Grafting to Traumatic and Arthritic Defects in the Knee Joint (2-7 Years Follow-Up), downloaded from http:webarchive.Org/web/20041205005845/http://www.stoneclinic.com/onestepthm:published Dec. 5, 2004.
Sun et. al., 2001, Quantitative imaging of gene induction in living animals, Gene Therapy, 8:1572-1579.
Supplementary European Search Report for EP 03720833, with date of completed search as Apr. 11, 2008.
Supplementary European Search Report for EP 04706268, with date of completed search as Jan. 12, 2011.
Supplementary European Search Report for EP 05728956.3, with date of completed search as May 2, 2011.
Supplementary European Search Report for EP 07827173, with date of completed search as Oct. 30, 2009.
Supplementary European Search Report for EP02753826 dated Jul. 17, 2009, 2 pages.
Supplementary European Search Report for EP08768602 dated Oct. 22, 2012, 6 pages.
Supplementary European Search Report for EP087983003.3 dated Oct. 18, 2012, 6 pages.
Taylor et. el., 2002, In vitro osteoclast resorption of bone substitute biomaterials used for implant site augmentation: a pilot study, Int J Oral Maxillofac Implants, 17(3):321-30.
Thomson et. al., 1995, Fabrication of Biodegradable Polymer Scaffolds to Engineer Trabecular Bones, J Biomater Sci Polymer Edn, 7(1) :23-38.
Thuerauf et. al., 1997, Differential Effects of Protein Kinase C, Ras, and Raf-1 Kinase on the Induction of the Cardiac B-type Natriuretic Peptide Gene through a Critical Promoter-proximal M-CAT Element, J Biol Chem., 272:7464-7472.
Tokuriki et. al., 2009, Stability effects of mutations and protein evolvability, Current Opinion in Structural Biology, 19:596-604.
Tozer et. al., 2005, Tendon and ligament: Development, repair and disease, Birth Defects Research Part C, 75(3):226-236.
Tsumaki et. al., 1999, Role of CDMP-1 in Skeletal Morphogenesis: Promotion Mesenchymal Cell Recruitment and Chondrocyte Differentiation, J Cell Biol., 144(1):161-173.
Ui-Tei et, al., 2004, Guidelines forthe selection highly effective siRNA sequences for mammlian and chick RNA interference, NAR 32(3):936-48.
U.S. Appl. No. 10/982,514, filed Nov. 5, 2004.
U.S. Appl. No. 10/982,514, Advisory Action dated Jun. 26, 2008.
U.S. Appl. No. 10/982,514, Advisory Action dated Oct. 23, 2008.
U.S. Appl. No. 10/982,514, Advisory Action dated Sep. 22, 2008.
U.S. Appl. No. 10/982,514, Final Office Action dated Feb. 1, 2008.
U.S. Appl. No. 10/982,514, Non-Final Office Action dated Jul. 17, 2007.
U.S. Appl. No. 10/982,514, Notice of Allowance dated Jan. 5, 2009.
U.S. Appl. No. 10/982,514, Requirement for Restriction/Election dated Apr. 4, 2007.
U.S. Appl. No. 12/416,435, Non-Final Office Action dated Mar. 22, 2011.
U.S. Appl. No. 12/416,435, Notice of Allowance dated Oct. 17, 2011.
U.S. Appl. No. 12/416,435, Restriction Requirement dated Dec. 10, 2010.
U.S. Appl. No. 13/347,823, Non-Final Office Action dated Nov. 21, 2012.
U.S. Appl. No. 13/347,823, Notice of Allowance dated Apr. 30, 2013.
U.S. Appl. No. 13/347,823, Restriction Requirement dated Jul. 23, 2012.
Vajo et. al., 2000, The Molecular and Genet.ic Basis of Fibroblast Growth Factor Receptor 3 Disorders: The Achondroplasia Family of Skeletal Dysplasias Muenke Craniosynostosis, and Crouzon Syndrome with Acanthosis Nigricans, Endocrine Rev 21(1):23-39.
Venkatesan et. al., 2004, Stimulation of proteoglycan synthesis by glucunosyltransferas-1 gene delivery: a strategy to promote cartilage repair, PNAS, 11(52):18087-92.
Verbruggen et. al., 1985, Repair Function in Organ Cultured Human Cartilage. Replacement of Enzymatically Removed Proteoglycans During Long term Organ Culture, The Journal of Rheumatology, 12(4).665-674.
Vidal et. al., 2005, Making sense of antisense, European Journal of Cancer, 41:2812-2818.
Vunjak-Novakovic et. al., 1999, Bioreactor Cultivation Conditions Modulate the Composition and Mechanical Properties of Tissue-Engineered Cartilage; Journal of Orthopaedic Research, 17:130-138.
Wade et. al., 1992, Codon usage tabulated from the GenBank genetic sequence data, Nucleic Acids Research, 20 (Supplernent):2111-2118.
Walsh et. al., 2003, Multiple tissue-specific promoters control expression of the murine tartrate-resistant acid phosphatase gene, Gene, 307:111-123.
Wang et. al., 1999, Overexpression of protein kinase C-? in the epidermis of transgenic mice results in striking alterations in phorbol ester-induced inflammation and COX-2, MIP-2 and TNF-alpha expression but not tumor promotion, Journal of Cell Science, 112:3497-3506.
Wells et. al., 1990, Additivity of Mutational Effects in Proteins Biochemistry, 29(37):8509.
Wilson et. al., 1977, Biological Properties of Polio Virus Encapsulated in Lipio Vesicles, Proc Natl Acad Sci, 74(8):3471-3475.
Winkler, 2013, Oligonucleotide conjugates for therapeutic applications, Ther Deliv., 4:791-809.
Wise et. al., 2002, American Surgeon, 68(6):553-end.
Wong et. al., 1995, Analysis of Putative Haparin-binding Domains of Fibroblast Growth Factor-1: Using Site-Directed Mutagenesis and Peptide Analogues, The Journal of Biological Chemistry, 270(43):25805-25811.
Woods at. al., 2005, Effectiveness of three extraction techniques in the development decellularized bone-anterior cruciate ligament-bone graft, Biomaterials, 26:7339-7349.
Written Opinion for PCT/IL2007/0011199, dated Sep. 16, 2008.
Written Opinion of the International Searching Authority Application No. PCT/IL2004/000088, dated Aug. 18, 2004.
Wu et. al., 2009, Multiple Synostoses Syndrome is Due to a Missense Mutation in Exon 2 of FGF9 Gene, The American Journal of Human Genetics, 85:53-63.
Yamashita et. al., 2000, Identification of a Novel Fibroblast Growth Factor, FGF-23, Preferentially Expressed in The Ventrolateral Thalamic Nucleus of the Brain, Biochemical and Biophysical Research Communications, 277:494-498.
Yang et. al., 1998, Improved fluorescence and dual color detection with enhanced blue and green variants of the green fluorescent protein, Journal of Biological Chemistry, 273:8212-6.
Yang et. al., 2000, Rac2 stimulates Akt activation affecting BAD/Bcl-XL expression while mediating survival and actin function in primary mast cells, Immunity, 12(5):557-568.
Yayon et, al., 1991, Cell Surface, Heparin-Like Molecules Are RequiredForBinding of Basic Fibroblast Growth Factor to Its High Affinity Receptor, Cell, 64:841-848.
Yayon et, al., 1993, Isolation of peptides that inhibit binding of basic fibroblast growthfactor to its receptor from a random phage-epitope library, Proc. Natl. Acad. Sci. USA, 90:10643-10647.
Yee et. al., 2000, Analysis of Fibroblast Growth Factor Receptor 3 S249C Mutation in Cervical Carcinoma, Journal of the National Cancer Institute, 92(22):1848-1849.
Young's Modulus, Entry on http://enwikipecliaorg accessed Oct, 27, 2005, 3 pages.
Zhang et. al., 1991, Three-dimensional structure of human basic fibroblast growth factor, a structural homology of interleukin 1 Beta, Proc. Natl. Acad. Sci. USA, 88(8):3446-3450.
Zhang et. al., 1997, Directed evolution of a fucosidase from a galactosidase by DNA shuffling anti screening, Proc. Natl. Acad. Sci. USA, 94:4504-4509.
Farndale et. al., 1982, A Direct Spectrophatometric Microassay for Sulfated Glycosaminoglycans in Carthage Cultures, Connective Tissue Research, 9(4):247-248.
Feczko et. al., 2003, Experimental Results of Donor Site Filling for Autologous Osteochondral Mosaicplasty, Arthroscopy: The Journal of Arthroscopic and Related Surgery, 19(7):755-761.
Final Office Action for U.S. Appl. No. 11/081,103, dated Aug. 11, 2010.
Fingl et. al., 1975, The Pharmacological Basis of Therapeutics, Ch 1:1.
Foldynova-Traritirkove et. al., 2012, Sixteen years and counting: the current understanding of fibroblast growth factor receptor 3 (FGFR3) signaling in skeletal dysplasias, Human Mutation, 33:29-41.
Fujibayashi et. al., 2001, J Long Term Eff Med implants:11:93-103.
Fujisato et. al., 1996, Effect of basic fibroblast growth factor on cartilage regeneration in chondrocyte-seeded collagen sponge scaffold, Biomaterials, 17:155-162.
Furth, et. al., 1994, Temporal control of genexpression in transgenic mice by a tetracycline-responsive promoter, Proc Natl Acad Sci USA, 91:9302-9306.
Gao et. al., 2002, Repair of Osteochondral Defect with Tissue-Engineered Two-Phase Composite Material Injectable Calcium Phosphate and Hyaluronan Sponge, Tissue Engineering Part A 8(5):827-837.
Gargiulo et. al., 2002, Phenotypic modulation of human articular chondrocytes by bistratene A, Eur Cell Mater, 3:9-18.
Garofalo et. al., 1999, Skeletal Dysplasia and Defective Chondrocyte Differentiation by targeted Overexpression of Fibroblast Growth Factor 9 in Transgenic Mice, Journal of Bone and Mineral Research, 14(11):1909-1915.
George et. al., 2006, Differentiation of Mesenchymal Stem Cells Into Osteoblasts on Honeycomb Collagen Scaffoids, Artificial Organs, 25(3):180-186.
George et. al., 2008, Biodegradable honeycomb collagen scaffold for dermal tissue engineering, J Biomed Mater Res 87A:1103-1111.
Gertzman et. al., 2001, A pilot study evaluating sodium hyaluronate as a carrier for freeze-dried demineralized bone powder, Cell and Tissue Banking, 2:87-94.
Gilbert et. at., 2006, Decellularization of Tissues and Organs, Biomaterials, 27(19):3675-3683.
Givol et. al., 1992, Complexity of FGF receptors: genetic basis for structural diversity and functional specificity, FASEB J., 6:3362-3369.
Glowacki et. al., 2001, Engineered Cartilage, Bone, Joints and Menisci-Potential for Temporomandibular Joint Reconstruction, Cells Tissues Organs, 189(3):302-308.
Goldberg et. al., 2005, Intra-articular hyaluronans: the treatment knee pain in osteoarthritis, Osteoarthritis Cartilage, 13(3):216-224.
Gooch et.al., 2001, IGF-I and Mechanical Environment Interact to Modulate Engineered Cartilage Development, Biochemical and Biophysical Research Communications, 286:909-915.
Gruber et, al., 2002, Platelets stimulate proliferation of bone cells: involvement of platelet.derived growth factor, microparticles and membranes, Clin Oral Implants Res., 13(5):529-535.
Guilak et. al., 2001, Functional tissue engineering: the role of biomechanics in articular cartilage repair. Clin Orthop Relat Res., (391 Suppl):S295-305.
Haisch et. al., 2000, Preparation of a pure autologous biodegradable fibrin matrix for tissue engineering, Cellular Engineering, Medical & Biological Engineering & Computing, 38:686-689.
Hayes et. al., 2002, Combining computational and experimental screening for rapid optimization ofprotein properties, Proc Nati Aced Sci U S A, 99:15926-31.
Hecht et. al., Structure of fibroblast growth factor 9 shows a symmetric dimer with unique receptor- and heparin-binding inerfaces, Acta Crysallogr D Biol Crystallogr, 57:378-384.
Herrera-Estrella et. al., 1983, Chimeric genes as dominant selectable markers in plant cells, EMBO J., 2(6):987-995.
Hidaka et. al., 2003, Acceleration of cartilage repair by genetically modified chondrocytes overexpressing bone morphogenetic protein-7, J Orthop Res, 21(4):573-83.
Hille et. al., 1990, Bleomycin resistance: a new dominant selectable marker for plant cell transformation, Plant Molecular Biology, 7:171-176.
Hoffman, 2002, Hydrogels for Biomedical Applications, Advanced Drug Delivery Reviews, 54(1):3-12.
Hromas et. al., 1993, Hematopoietic lineage-and stage-restricted expression the ETS oncogene family member PU.1, Blood 82:2998-3004.
http://www.stoneclinic.com/articularcartilagepastegrafting (Copyright 2009).
http://www.technobusiness-solutions.com/article-lyophilization1.html (published Feb. 12, 2002).
Hunziker, 1992, Articular Cartilage Structure in Humans and Experimental Animals, Articular Cartilage and Osteoarthritis, Raven Press, ed:183-199.
Hunziker, 1999, Articular cartilage repair: are the intrinsic biological constraints undermining this process insuperable?, Osteoarthritis and Cartilage 7(1):15-28.
Hunziker, 2001, Articular Cartilage Repair: Basic Science and Clinical Progress A Review of the Current Status and Prospects, Osteoarthritis and Cartilage, 10(6):432-463.
Ikeda et. al., 2000, Ex vivo gene delivery using an adenovirus vector in treatment for cartilage defects, J Rheumatol, 27(4):990-6.
lmamura et. al., 1990, Recovery of Mitogenic Activity of a Growth Factor Mutant with a Nuclear Translocation Sequence, Science, 249:1567-1570.
International Cartilage Repair Society, Cartilage Injury Evaluation Package, www.cartilage.org, 2000.
International Preliminary Examination Report for PCT/US02/09001 dated Oct. 30, 2004, (7 pages).
International Preliminary Report on Patentability Application No. PCT/IL2004/000088, dated Aug. 5, 2005.
International Preliminary Report on Patentability for International Patent Application No. PCT/US2004/010956, dated Nov. 18, 2005.
International Preliminary Report on Patentability for International Patent Application No. PCT/US2004/010957, dated Nov. 18, 2005.
International Preliminary Report on Patentability for International Patent Application No. PCT/US2005/008798 dated Nov. 1, 2006.
International Preliminary Report on Patentability for InternationalPatent Application No. PCT/US2005/030610, dated Feb. 26, 2008.
International Preliminary Report on Patentability for International Patent Application No. PCT/US2005/036878, dated Apr. 17, 2007.
International Preliminary Report on Patentability for International Patent Application No. PCT/US2008/051796, dated Jul. 28, 2009.
International Preliminary Report on Patentability for PCT/IL2001/00962, dated Oct. 18, 2006.
International Preliminary Report on Patentability for PCT/IL2007/001199 dated Mar. 21, 2009.
International Preliminary Report on Patentability for PCT/US2008/073762 dated Feb. 24, 2010, (6 pages).
International Preliminary Report on Patentability for PCT/US2009/001459, dated May 12, 2010.
International Search Report and Written Opinion for international Patent Application No. PCT/US2004/010956, dated Oct. 28, 2005.
Apr. 4, 2007 Requirement for Restriction/Election U.S. Appl. No. 10/982,514 (U.S. Pat. No. 7,563,769).
Jul. 17, 2007 Non-Finai Rejection U.S. Appl. No. 10/982,514 (U.S. Pat. No. 7,563,769).
Sep. 22, 2008 Advisory Action U.S. Appl. No. 10/982,514 (U.S. Pat. No. 7,563,769).
Advisory Action dated Oct. 23, 2008 for U.S. Appl. No. 10/982,514.
Advisory Action, dated Jun. 26, 2008, for U.S. Appl. No. 10/982,514.
Advisory Action, dated Sep. 22, 2008, for U.S. Appl. No. 10/982,514.
Final Office Action, dated Feb. 1, 2008, for U.S. Appl. No. 10/982,514.
Non-Final Office Action, dated Dec. 15, 2006, for U.S. Appl. No. 10/895,961.
Non-Final Office Action, dated Jul. 17, 2007, for U.S. Appl. No. 10/982,514.
Non-Final Office Action, dated Jun. 20, 2005, for U.S. Appl. No. 10/761,615.
A non-final Office Action dated Jan. 20, 2011 in connection with U.S. Appl. No. 12/381,072.
A non-final Office Action dated Mar. 1, 2011 in connection with U.S. Appl. No. 12/924,132.
Abbate et. al., 2001, Biotechniques 3 1:336-40.
Abraham et. al., 1996, Human Basic Fibroblast Growth Factor: Nucleotide Sequence and Genomic Organization, EMBO Journal., 5(10):2523-2528.
Agrawal et. al., 1991, Pharmacokinetics, Biodistribution, and Stabilityof Oligodeoxynucleotide Phosphorothioates in Mice, PNAS, 88:7595-7599.
Altschul et. al., 1990, Basic Local Alignment Search Tool, J Mol Biol 215:403-410.
Andres et. al., 2008, A Pro-Inflammatory Signature Mediates FGF2-nduced Angiogenesis, Journal of Cellular and Molecular Medicine, 13(8B):2083-2108.
U.S. Appl. No. 11/190,387, Advisory Action, dated Dec. 16, 2008 (16 pages).
U.S. Appl. No. 11/190,387, Advisory Action, dated Feb. 11, 2009 (7 pages).
U.S. Appl. No. 11/190,387, Advisory Action, dated Jan. 14, 2008 (3 pages).
U.S. Appl. No. 11/190,387, Advisory Action, dated Oct. 31. 2008 (15 pages).
U.S. Appl. No. 11/190,387, Final Rejection, dated Aug. 26, 2008 (12 pages).
U.S. Appl. No. 11/190,387, Final Rejection, dated Aug. 6, 2007 (18 pages).
U.S. Appl. No. 11/190,387, Non-Finai Rejection, dated Mar. 27, 2007 (21 pages).
U.S. Appl. No. 11/190,387, Non-Finai Rejection, dated Mar. 27, 2008 (11 pages).
U.S. Appl. No. 11/190,387, Requirement for Restriction/Eiection, dated Sep. 7, 2006 (7 pages).
U.S. Appl. No. 12/731,356, Non-Finai Rejection, dated Mar. 29, 2011 (14 pages).
U.S. Appl. No. 12/731,356, Requirement for Restriction/Eiection, dated Dec. 23, 2010 (6 pages).
Arai et. al., 2000, Gene delivery to human chondrocytes by an adeno associated virus vector J Rheumatol 27(4):979-82.
Arai et. al., 2004, Effect of adenovirus-mediated overexpression of bovine ADAMTS-4 and human ADAMTS-5 in primary bovine articuiar chondrocyte pellet culture system Osteoarthritis Cartilage, 8:599-613.
Arakawa et. al., 1993, Production and Characterization of an Analog of Acidic Fibroblast Growth Factor With Enhanced Stability and Biological Activity, Protein Engineering, 6(5):541-546.
Aston et ai., 1986, Repair of Articuiar Surfaces by Allografts of Articular and Growth-Plate Cartilage, Journal of Bone and Joint Surgery, 68-B(1):29-35.
Attwood, 2000, The Babel of bioinfonmatics, Science, 290:471-473.
Aviezer et. al., 1994, Differential Structural Requirements of Heparin and Heparan Sulfate Proteoglycans That Promote Binding of Basic Fibroblast Growth Factor To Its Receptor, The Journal of Biological Chemistry, 269(1):114-121.
Aviles et. al., 2003, Testing clinical therapeutic angiogenesis using basic fibrobiast growth factor (FGF-2), British Journal of Pharmacology, 140:637-646.
Bailly et. al., 2000, Uncoupling of Cell Proliferation and Differentiation Activities of Basic Fibroblast Growth Factor, FASEB Journal., 14:333-344.
Baird, 1994, Fibroblast growth factors: activities and significance of non-neurotrophin neurotrophic growth factors, Current Opinions in Neurobioiogy, 4:78-86.
Bange et. al., 2002, Cancer Progression and Tumor Cell Motility are Associated with the FGFR4 Arg 388 Allele, Cancer Research, 62:840-846.
Baragi et. al., 1995, Transplantation of transduced chondrocytes protects articular cartilage from interleukin 1-induced extracellular matrix degradation, J. Ciin. Invest. 96(5):2454-60.
Barralet et. al., 2000, Dissolution of dense carbonate apatite subcutaneously implanted in Wistar rats, J Biomed Mater Res, 49(2):176-82.
Bartholomew et. al., 1997, The Evi-1 proto-oncogene encodes a transcriptional repressor activity associated with transformation, Oncogene, 14:569-577.
Behr et. al., 2010, Fgf-9 is required for angiogenesis and osteogenesis in long bone repair, PNAS, 107(26):11853-11858.
Bellosta et. al., 2001, Identification of Receptor and Heparin Binding Sites in Fibrobiast Growth Factor 4 by Structure-Based Mutagenesis, Molecular and Cellular Biology 21(17):5946-5957.
Ben-Bassat et. al., 2000, in Biomateriais Engineering and Devices: Human Applications v2:155-169.
Berclaz et. al., 2002, regulates alveolar macrophage Fe?R-mediated phagocytosis and the IL-18/IFN?-mediated molecular connection between innate and adaptive immunity in the lung, Blood, 100:4193-4200.
Beynnon et. al., 2005, Treatment of Anterior Cruciate Ligament Injuries Part 2, The American Journal of Sports Medicine, 33(11):1751-1767.
Beynnon, et. al., 2005, Treatment of Anterior Cruciate Ligament Injuries Part 1, The American Journal of Sports Medicine, 33(10):1579-1602.
International Search Report and Written Opinion for International Patent Application No. PCT/US2004/010957, dated Nov. 1, 2004.
International Search Report and Written Opinion for International Patent Application No. PCT/US2005/008798, dated Jun. 19, 2006.
International Search Report and Written Opinion for International Patent Application No. PCT/US2005/030610, dated Apr. 7, 2006.
International Search Report and Written Opinion for International Patent Application No. PCT/US2005/036878, dated Sep. 21, 2006.
International Search Report and Written Opinion for International Patent Application No. PCT/US2008/085522, dated Jul. 6, 2009.
International Search Report and Written Opinion for International Patent Application No. PCT/US2008/001459, dated Jul. 6, 2009.
International Search Report and Written Opinion for PCT/US2008/007610 dated Oct. 8, 2008.
International Search Report and Written Opinion for PCT/US2010/000108 dated Aug. 24, 2010.
International Search Report for PCT/IL02/00589 dated Mar. 26, 2003.
International Search Report for PCT/US02/09001 dated Mar. 27, 2003, (2 pages).
Itoh et. al., 2001, A Honeycomb Collagen Carrier for Cell Culture as a Tissue Engineering Scaffold, Artificial Organs, 25(3):213-217.
Itokazu et. al., 1997, The Sustained Release of Antibiotic from Freeze-Dried Fibrin Antibiotic Compound and Efficacies in a Rat Model of Osteomyelitis, Infection, 25(6):359-363.
Iwamoto et. al., 1991, Reduction in Basic Fibroblast Growth Factor Receptor is Coupled with Terminal Differentiation of Chondrocytes, J Biol Chem 266(1):461-467.
Jackson et. al., 2001, Cartilage Substitute: Overview of Basic Science & Treatment Options, Journal of American Academy of Orthopaedic Surgeons, 9:37-52.
Jacobi et. al., 2011, MACI—a new era?, Arthoscopy, Rehabilitation, Therapy & Technology, http://www.smartjournal.com/content/3/1/10.
James et. al., 2000, Genetic manipulation of the rabbit heart via transgenesis, Circulation, 101:1715-1721.
Johnson et. al., 1993, Structural and Frunctional Diversity in the FGF Receptor Multigene Family, Advances in Cancer Research, 60:1-41.
Karlin et. al., 1990, Methods for assessing the statistical significance of molecular sequence features by using general scoring schemes, Proc. Natl. Acad. Sci. USA, 87:2264-2268.
Karlin et. al., 1993, Applications and statistics for multiple high-scoring segments in molecular sequences, Proc. Natl. Acad. Sci. USA, 90:5873-5877.
Kastrup et. al., 1997, X-rat Structure of the 154-Amino-Acid Form of Recombinant Human Basic Fibroblast Growth Factor Comparison with the Truncated 146-Amino-Acid Form, Acta Crystallographica, Section D53:160-168.
Kato et. al., 1990, Fibroblast Growth Factor is an Inhibitor of Chondrocyte Terminal Differentiation, Journal of Biological Chemistry, 265(10):5903-5909.
Keegan et. al., 1991, Isolation of an additional member of the fibroblast growth factor receptor family, FGFR-3, Proc. Natl. Acad. Sci. USA, 88:1095-1099.
Kiewitz et. al., 2009, Transcriptional regulation of S100A1 and exparession during mouse heart development, Biochim Biophys Acts, 1498:207-19.
Kim et. al., 2002, Alternative type I and I? turn conformations in the ?8/?9 ?-hairpin of human acidic fibroblast growth factor, Protein Science, 11(3):459-66.
Kirikoshi, 2000, Molecular Cloning and Characterization of Human FGF-20 on Chromosome 8p21.3-p22, Biochemical and Biophysical Research Communications, 274(2):337-343.
Kirker et. al., 2002, Glycosaminoglycan Hydrogel Films as Biointeractive Dressings for Wound Healing, Biomaterials, 23:3661-3671.
Kondo et. al., 2005, Effects of Administration of Exogenous Growth Factors on Biomechanical Properties of the Elongation-Type Anterior cruciate Ligament Infury With Partial Laceration, The American Journal of Sports Medicine, 33:188-196.
Kunkel, 1985, Rapid and efficient site-specific mutagenesis without phenotypic selection, Proc. Natl. Acad. Sci. USA, 82:488-492.
Kuroda et. al., 1999, Anabolic Effect of Amino terminally Truncated Fibroblast Growth Factor 4 (FGF4) on Bone, Bone, 25(4):431-437.
Kurokawa et. al., 2000, The Evi-1 oncoprotein inhibits c-Jun N-terminal kinase and prevents stress-induced cell death, EMBO J., 19:2958-2968.
Kuroyanagi et. al., 2001, Tissue-Engineered Product: Allogeneic Cultured Dermal Subsitute Composed of Spongy Collagen with Fibroblasts, Artificial Organs, 25(3):180-186.
Lakso et. al., 1992, Targeted oncogene activation by site-specific reombination in transgenic mice, Proc. Natl. Acad. Sci. USA, 89:6232-6236.
LaPointe et. al., 1996, Tissue-specific expression of the human brain natriuretic peptide gene in cardiac myocytes, Hypertension, 27:715-722.
Lev et. al., 1992, Dimerization and Activation of the Kit Receptor by Monovalent and Bivalent Binding of the Stem Cell Factor, The Journal of Biological Chemistry, 267, 15970-15977.
Li et. al., 2004, Synthesis and biological evaluation of a cross-linked hyaluronan-mitomycin C hydrogel, Biomacromolecules, 5(3):895-902.
Loeser et. al., 2005, Basic Fibroblast Growth Factor Inhibits the Anabolic Activity of Insulin-like Growth Factor 1 and Osteogenic Protein 1 in Adult Human Articular Chondrocytes, Arthritis & Rheumatism, 52(12):3910-3917.
Lorget et. al., 2012, Evaluation of the Therapeutic Potential of a CNP Analog in a Fgfr3 Mouse Model Recapituating Achondroplasis, Am J Hum Genet., 91(6):1108-1114.
Lu et. al., 2006, Minced Cartilage without Cell Culture Serves as an Effective Intraoperative Cell Source for Carilage Repair, Journal of Orthopaedic Research, 24:1261-1270.
Luo et. al., 1999, Synthesis and selective cytotoxicity of a hyaluronic acid-antitumor bioconjugate, Bioconjugate Chemicals, 10(5):755-763.
Madry et. al., 2003, Sustained transgene expression in cartilage defects in vivo after transplantation of articular chondrocytes modified by lipid-mediated gene transfer in a gel suspension delivery system, J Gene Med, 5(6):502-9.
Madry et. al., 2000, Efficient lipid-medicated gene transfer to articular chondrocytes, Gene Ther 7(4):286-91.
Madry et. al., 2002, Gene Transfer of a Human Insulin-like Growth Factor I cDNA Enhances Tissue Engineering of Cartilage, Human Gene Therapy, 13:1621-1630.
Madry et. al., 2003, Recombinant adeno-associated virus vectors efficiently and persistently transduce chondrocytes in normal and osteoarthritic human articular cartilage, Hum Gene Ther, 14(4):393-402.
Marian et. al., 1999, A transgenic rabbit model for human hypertrophic cardiomyopathy, J Clin Invest., 104:1683-1692.
Matsuda et. al., 1995, In Vivo Chrondrogenesis in Collagen Sponge Sandwiched by Perichondrium, J Biomater Sci Polymer Ed, 7(3):221-229.
Mazue et. al., 1991, Preclinical and Clinical Studies with Recombinant Human Basic Fibroblast Growth Factor, Annals New York Academy of Sciences:329-340.
Mbawuike et. al., 1989, a murine alveolar macrophage cell line: morphological, cytochemical, and functional characteristics, J Leukoc Biol., 46:119-127.
McKercher et. al., 1996, Targeted disruption of the PU.1 gene results in multiple hematopoietic abnormalities, EMBO J., 15:5647-5658.
McLeskey et. al., 1994, MDA-MB-134 Breast Carcinoma Cells Overexpress Fibroblast Growth Factor (FGF) Receptors and Are Growth-Inhibited by FGF Ligands, Cancer Research 54(2):523-530.
Messner et. al., 1996, Cartilage Repair: A Critical Review, Acta Orthopaedica Scandinavica, 67(5):523-529.
Bikfalvi et al., 1997, Biological Roles of Fibroblast Growth Factor-2, Endocrine Reviews, 18(1):26-45.
Blessing et. al., 1993, Transgenic mice as a model to study the role of TGF-beta-related molecules in hair follicles, Genes Dev, 7:204-215.
Bolander, 1992, Regulation of fracture repair by growth factors, Proc Soc Exp Biol Med., 200(2):165-170.
Bork et. al., 1996, Go hunting in sequence databases but watch out for the traps, Trends in Genetics 12(10):425-427.
Bork, 2000, Powers and pitfaiis in sequence analysis: The 70% hurdle. Genome Res 10(4):398-400.
Borok et. al., 2000, Differential regulation of rat aquaporin-5 promoter/enhancer activities in lung and salivary epithelial cells, J Biol Chem, 275:26507-14.
Bradford, 1976, A Rapid and Sensitive Method for the Quantitation of Micro-gram Quantities of Protein Utilizing the Principle of Protein-Dye Binding, Analytical Biochemistry, 72(1-2):248-254.
Bradley, 1987, Production and analysis of chimaeric mice. In Teratocarcinomas and Embryonic Stem Cells—A Practica Approach:113-152.
Breinan et. el., 1997, Effect of Cultured Autologous Chondrocytes on Repair of Chondral Defects in a Canine Model, Journal of Bone and Joint Surgery [Am], 79-A(10):1439-1451.
Breinan et al., 2001, Autologous Chondrocyte Implantation in a Canine Model: Change in Composition of Reparative Tissue with Time, Journal of Orthopaedic Research. 19:482-492.
Brenner, 1999, Errors in genome annotation, Trends in Genetics 15(4):132-133.
Brittberg et. al., 1994, Treatment of Deep Cartilage Defects in the Knee with Autologous Chondrocyte Transplantation, New England Journal of Medicine, 331(14):889-895.
Brittberg et. al., 1996, Rabbit Articular Cartilage Defects Treated with Autologous Cultured Chondrocytes, Clinical Orthopaedics and Related Research, 326:270-283.
Brittberg et. al., 2001, Autologous Chondrocytes Used for Articular Cartilage Repair: An Update, Clinical Orthopaedics and Related Research. 391 Suppl: S337-S348.
Brown et. al., 2005, Hyaluronic acid: a unique topical vehicle for the localized delivery of drugs to the skin, JEADV, 19(3):308-318.
Buckwalter et. al., 1998, Articular Cartiiage; Degeneration and Osteoarthritis, Repair, Regeneration, and Transplantation, AAOS Instructional Course Lectures, 47:487-504.
Bugbee, 2000, Fresh Osteochondral Allografting, Operative Techniques in Sports Medicine, 8(2):158-162.
Bujard, 1999, Controlling genes with tetracyclines, J Gene Med, 1:372-374.
Bulpitt et. al., 1999, New strategy for chemical modification of hyaluronic acid: Preparation of functionalized derivatives and their use in the formation of novel biocompatible hydrogels, J Biomed Mater Res, 47:152-169.
Burdette et. al., 1996, Cloning and expression of the gene encoding the Thermoanaerobacter ethanaiicus 39E secondary-alcohol dehydrogenase and biochemical characterization of the enzyme, Biochem J, 316:115-122.
Burger et. al., 2002, Fibroblast growth factor receptor-1 is expressed by endotheliai progenitor cells, Blood, 100(10):3527-35.
Bursac, 2002, Collagen Network Contributions to Structure-Function Relationships in Cartilaginous Tissues in Compression (Dissertation), Boston University College of Engineering.
Bystricky et. al., 2001, Nonbiodegradabie hyaluronan derivative prepared by reaction with a water-soluble carbodiimide Chem Paper, 1:49-52.
Cappellen et. al., 1999, Frequent Activating Mutations Of FGFR3 In Human Bladder And Cervix Carcinomas, Nature Genetics, 23:18-20.
Carr, 1988, Fibrin formed in plasma is composed of fibers more massive than those formed from purified fibrinogen, Thromb Haemost., 59(3):535-539.
Chalfie et. al., 1994, Green fluorescent protein as a marker for gene expression, Science 263:802-805.
Charron et. al., 1999, Cooperative Interaction between GATA-4 and GATA-6 Regulates Myocardial Gens Expression, Molecular & Cellular Biology 19(6):4355-4365.
Chellaiah et. al., 1994, Fibroblast Growth Factor Receptor (FGFR) 3. The Journal of Biological Chemistry 269(15):11620-11627.
Chen et. al., 1999, Repair of Articular Cartilage Defects: Part I Basic Science of Cartilage Healing, The American Journal of Orthopedics:31-33.
Chole et. al., 2001, JARO 2:65-71.
Chusho et. al., 2001, Dwarfism and Early Death in Mice Lacking C-Type Natriuretic Peptide, PNAS, 98(7):4016-4021.
Coffin et. al., 1997, Retroviruses Cold Spring Harber Laboratory Press:758-763.
Coiombier et. al., 1999, Cells Tissues Organs 164:131-140.
Communication pursuant to Article 94(3) EPC for European Patent Application No. 06814983.0, dated Sep. 23, 2013, 6 pages.
Cook et. al., 2003, Biocompatibiiity of three-dimensional chondrocyte grafts in large tibial defects of rabbits, Am J Vet. Res 64(1):12-20.
A Communication dated Oct. 9, 2007 in connection with U.S. Appl. No. 10/438,883.
A final Office Action dated Dec. 28, 2009 in connection with U.S. Appl. No. 11/657,042.
A final Office Action dated Jan. 7, 2010 in connection with U.S. Appl. No. 11/481,955.
A final Office Action dated Mar. 15, 2010 in connection with U.S. Appl. No. 10/815,778.
A final Office Action dated Nov. 13, 2008 in connection with U.S. Appl. No. 10/815,778.
A final Office Action dated Oct. 18, 2005 in connection with U.S. Appl. No. 10/438,883.
A final Office Action dated Sep. 19, 2008 in connection with U.S. Appl. No. 11/081,105.
A final Office Action dated Sep. 28, 2007 in connection with U.S. Appl. No. 10/960,960.
Advisory Action dated Dec. 27, 2007 in connection with U.S. Appl. No. 11/151,270.
Final Office Action dated Mar. 22, 2010 in connection with U.S. Appl. No. 12/010,984.
Final Office Action dated Oct. 9, 2007 In connection with U.S. Appl. No. 11/151,270.
Non-Finai Office Action dated Apr. 12, 2010 in connection with U.S. Appl. No. 12/191,490.
Non-Final Office Action dated Apr. 15, 2010 in connection with U.S. Appl. No. 11/657,042.
Non-Final Office Action dated Apr. 15, 2010 in connection with U.S. Appl. No. 12/079,629.
Non-Final Office Action dated Apr. 26, 2010 in connection with U.S. Appl. No. 12/147,042.
Related Publications (1)
Number Date Country
20190010439 A1 Jan 2019 US
Divisions (1)
Number Date Country
Parent 14558080 Dec 2014 US
Child 16131234 US