Transplant/implant device and method for its production

• US 8,137,689 B1
• Filed: 11/13/2000
• Issued: 03/20/2012
• Est. Priority Date: 11/11/1999
• Status: Active Grant

• Current Assignee: Zimmer GmbH (Zimmer Biomet Holdings, Inc.)
• Original Assignee: Zimmer GmbH (Zimmer Biomet Holdings, Inc.)
• Inventors: Mainil-Varlet, Pierre, Müller, Werner, Grogan, Shawn P., Schaffner, Thomas
• Primary Examiner(s): Nguyen, Quang
• Application Number:
  US10/129,915
• Time in Patent Office: 4,145 Days
• Field of Search: 424/423, 424/424, 424/425, 424/426, 523/113, 523/114
• US Class Current: 424/425
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 35/32 Bones; Osteocytes; Osteoblasts; Tendons; Tenocytes; Teeth; Odontoblasts; Cartilage; Chondrocytes; Synovial membrane
• CPC Class Codes: A61K 38/185 Nerve growth factor [NGF]; Brain derived neurotrophic factor [BDNF]; Ciliary neurotrophic factor [CNTF]; Glial derived neurotrophic factor [GDNF]; Neurotrophins, e.g. NT-3
• CPC Class Codes: A61K 38/1875 Bone morphogenic factor; Osteogenins; Osteogenic factor; Bone-inducing factor
• CPC Class Codes: A61K 38/20 Interleukins [IL]
• CPC Class Codes: A61K 38/28 Insulins
• CPC Class Codes: A61K 38/29 Parathyroid hormone, i.e. parathormone; Parathyroid hormone-related peptides
• CPC Class Codes: A61K 38/31 Somatostatins
• CPC Class Codes: A61K 38/36 Blood coagulation or fibrinolysis factors
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61L 2300/64 Animal cells
• CPC Class Codes: A61L 2430/06 for cartilage reconstruction, e.g. meniscus
• 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 27/3645 Connective tissue
• 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 27/3843 Connective tissue
• CPC Class Codes: A61L 27/3886 comprising two or more cell types
• CPC Class Codes: A61L 27/3895 using specific culture conditions, e.g. stimulating differentiation of stem cells, pulsatile flow conditions
• CPC Class Codes: A61L 27/54 : Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61P 17/02 : for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 19/02 : for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 21/04 : for myasthenia gravis
• CPC Class Codes: A61P 25/00 : Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/16 : Anti-Parkinson drugs
• CPC Class Codes: A61P 25/28 : for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 29/00 : Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/10 : for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 5/02 : of the hypothalamic hormones, e.g. TRH, GnRH, CRH, GRH, somatostatin
• CPC Class Codes: A61P 5/18 : of the parathyroid hormones
• CPC Class Codes: A61P 5/48 : of the pancreatic hormones
• CPC Class Codes: A61P 7/04 : Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
• CPC Class Codes: C12N 5/0655 : Chondrocytes; Cartilage

Abstract

A transplant/implant device for delivering at least one predetermined biologically active compound to a human or animal host system or for another biological function in the host system is produced by genetically engineering vital chondrocytes or mixing chondrocytes with another type of native or genetically engineered cells or mixing chondrocytes with artificial particles having a size comparable to the size of cells or combining at least two of the named steps of engineering or mixing and by subjecting the chondrocytes or the mixture comprising the chondrocytes to three dimensional culture conditions for in vitro production of cartilaginous tissue whereby the cells and/or the artificial particles are immobilized in the cartilaginous tissue. The chondrocytes produce and maintain the cartilaginous tissue and the chondrocytes themselves or cells of another cell type immobilized in the cartilaginous tissue are able to produce and secrete the at least one predetermined compound.

Claims

1. An implant for in vivo production of at least one predetermined biologically active compound, said implant comprising chondrocytes producing and maintaining an extracellular matrix and artificial particles producing the at least one predetermined compound, wherein at least some of the artificial particles are disposed within the extracellular matrix and other than the artificial particles, the implant is generated in vitro without the use of a three dimensional artificial matrix.

2. The implant according to claim 1, wherein the chondrocytes comprise autologous chondrocytes originating from a human or animal into which the implant is to be implanted.

3. The implant according to claim 1, wherein the chondrocytes are heterologous or homologous chondrocytes.

4. The implant according to claim 1, further comprising genetically engineered cells.

5. The implant according to claim 4, wherein the genetically engineered cells are chondrocytes.

6. The implant according to claim 1, wherein the compound is selected from the group consisting of inhibitors of inflammation, hormones, growth factors, coagulation factors, neurotransmitters, neurotrophic factors, and activators or inhibitors of angiogenesis.

7. The implant according to claim 1, wherein the particles are of a size comparable to the size of the cells.

8. The implant of claim 1, wherein the extracellular matrix comprises type II collagen and proteoglycans.

9. The implant of claim 1, wherein the chondrocytes originate from cartilaginous tissue.

10. The implant of claim 1, wherein the chondrocytes are prepared by in vitro differentiation of stem cells or pre-chondrocytes.

11. The implant of claim 1, wherein at least some of the artificial particles disposed within the extracellular matrix are immobilized within the extracellular matrix.

12. The implant of claim 6, wherein the compound is a hormone selected from the group consisting of insulin, parathyroid hormone, and somatotropin.

13. The implant of claim 12, wherein the hormone is insulin.

14. The implant of claim 6, wherein the compound is a growth factor.

15. The implant of claim 14, wherein the growth factor is a bone morphogenic protein.