Method for composite cell-based implants

• US 6,662,805 B2
• Filed: 08/06/2001
• Issued: 12/16/2003
• Est. Priority Date: 03/24/1999
• Status: Expired due to Fees

• Current Assignee: Chondros, Inc.
• Original Assignee: Chondros, Inc., Johns Hopkins University
• Inventors: Bloom, Leonard, Domb, Abraham J., Fink, David J., Frondoza, Carmelita G., Hungerford, David S., Shikani, Alan H.
• Primary Examiner(s): McDermott, Corrine
• Assistant Examiner(s): BARRETT, THOMAS C
• Application Number:
  US09/922,909
• Publication Number:
  US 20010051834A1
• Time in Patent Office: 862 Days
• Field of Search: 623/23-2-, 128/898
• US Class Current: 128/898
• CPC Class Codes: A61F 2/08 Muscles; Tendons; Ligaments sutures A61B17/04
• CPC Class Codes: A61K 35/12 Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells vaccines or medicinal preparations containing antigens or antibodies A61K39/00
• CPC Class Codes: A61K 47/36 Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
• CPC Class Codes: A61K 9/0024 Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L
• CPC Class Codes: A61K 9/1652 Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin homeopathic globules A61K9/1623
• CPC Class Codes: A61K 9/5036 Polysaccharides, e.g. gums, alginate; Cyclodextrin
• CPC Class Codes: A61L 2400/06 Flowable or injectable implant compositions
• CPC Class Codes: A61L 27/3633 Extracellular matrix [ECM]
• CPC Class Codes: A61L 27/3641 characterised by the site of application in the body materials for artificial blood vessels A61L27/507; materials for use in artificial skin A61L27/60
• CPC Class Codes: A61L 27/3804 characterised by specific cells or progenitors thereof, e.g. fibroblasts, connective tissue cells, kidney cells
• CPC Class Codes: A61L 27/3813 Epithelial cells, e.g. keratinocytes, urothelial cells
• CPC Class Codes: A61L 27/3817 Cartilage-forming cells, e.g. pre-chondrocytes
• CPC Class Codes: A61L 27/3839 characterised by the site of application in the body materials for artificial blood vessels A61L27/507; materials for use in artificial skin A61L27/60
• CPC Class Codes: A61L 27/3852 Cartilage, e.g. meniscus
• CPC Class Codes: C08B 15/005 Crosslinking of cellulose derivatives
• CPC Class Codes: C08B 33/00 Preparation of derivatives of amylose
• CPC Class Codes: C08B 37/00 Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof cellulose D21; microbiological processes C12P
• CPC Class Codes: C08B 37/0021 Dextran, i.e. (alpha-1,4)-D-glucan; Derivatives thereof, e.g. Sephadex, i.e. crosslinked dextran
• CPC Class Codes: C08B 37/006 Heteroglycans, i.e. polysaccharides having more than one sugar residue in the main chain in either alternating or less regular sequence; Gellans; Succinoglycans; Arabinogalactans; Tragacanth or gum tragacanth or traganth from Astragalus; Gum Karaya from Sterculia urens; Gum Ghatti from Anogeissus latifolia; Derivatives thereof
• CPC Class Codes: C08H 1/00 Macromolecular products derived from proteins food proteins A23; glue, gelatine C09H
• CPC Class Codes: C08J 2305/08 : Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof
• CPC Class Codes: C08J 3/12 : Powdering or granulating
• CPC Class Codes: C12N 2500/02 : Atmosphere, e.g. low oxygen conditions
• CPC Class Codes: C12N 2531/00 : Microcarriers
• CPC Class Codes: C12N 2533/70 : Polysaccharides
• CPC Class Codes: C12N 2533/72 : Chitin, chitosan
• CPC Class Codes: C12N 5/0075 : using microcarriers
• CPC Class Codes: C12N 5/0654 : Osteocytes, Osteoblasts, Odontocytes; Bones, Teeth
• CPC Class Codes: C12N 5/0655 : Chondrocytes; Cartilage

Abstract

This invention is a method for the implantation of a combination of cells or cell-microcarrier aggregates wherein one component comprises a solid implantable construct and a second component comprises an injectable formulation. For example, in one embodiment, the solid implant may be first implanted to fill the majority of the cavity receiving the implant, and then cells or cell-microcarrier aggregates in an injectable format, with or without the addition of gelling materials to promote rapid gelling in situ, may be injected into spaces surrounding the solid implant in order to secure the solid implant in the site and/or to promote rapid adherence and/or integration of the solid implant to surrounding tissues. Also contemplated in this embodiment is that the cellular composition of the injectable component may differ from that of the solid component. For example, the solid implant may result from the culturing of chondrocytes on microcarriers or scaffolds, thereby resulting in an implant having cartilage-like properties, whereas the injectable cells or aggregates may result from the culturing of stem cells, resulting thereby in cells capable of producing cells of a chondrogenic, fibroblastic, myoblastic or osteoblastic phenotype. In this example, cells in the injectable aggregates may promote the fixation to or rapid integration of the solid cartilage implant into surrounding cartilage, connective tissue, muscle or bone, respectively.

Claims

1. A method for replacing a tissue or body part by filling a cavity or lesion of the tissue comprising (1) preparing a solid cell-containing implant from cells;

(2) preparing an injectable cell-containing formulation of cell-microcarrier aggregates;

(3) coating the surface of said cavity or lesion of the tissue with the injectable cell-containing formulation; and

(4) implanting the solid cell-containing implant into said cavity or lesion of the tissue such that the cavity or lesion of the tissue is in contact with the injectable cell-containing formulation.

2. The method of claim 1 wherein the cells are chondrocytes.

3. The method of claim 1 wherein the cells are selected from chondrocytes;

osteoblasts;

fibroblasts derived from skin, tendon, ligament, meniscus, disk or any other connective tissue;

stem cells derived from bone marrow stroma, muscle, skin or other stem cell-containing tissue;

embryonic stem cells;

or combinations of these cells that may be seeded onto the microcarrier.

4. The method of claim 1 wherein the cells used to prepared the solid implant differ from the cells used to prepare the injectable cell-containing formulation.

5. The method of claim 1 wherein the solid cell-containing implant is prepared by culturing cells on a solid scaffold.

6. The method of claim 1 wherein the solid cell-containing implant is prepared by culturing cells on microcarrier particles.

7. The method of claim 1 wherein the injectable cell-containing formulation is prepared by culturing cells on microcarrier particles.

8. The method of claim 1 wherein the injectable cell-containing formulation comprises a suspension of cells in a medium suitable for injection.

9. The method of replacing a tissue or body part or filling a void in a patient'"'"'s head or neck area comprising the steps of obtaining a non-diseased, cell sample from the respective patient'"'"'s head and neck area, rapidly growing additional cells obtained from said cell sample in a bioreactor to produce a suspension of cell-microcarrier aggregates, and further culturing some of the cell-microcarrier aggregates within a predetermined mold which is the mirror image of the patient'"'"'s tissue, body part or void, such that a molded tissue, body part or void is produced, and surgically implanting the molded tissue, body part or void in combination with an injectable suspension of cell-microcarrier aggregates as a replacement in the patient'"'"'s head and neck area, such that the implant regenerates therein and fuses with the adjacent tissues in the head and neck area of the respective patient.