Systems for cartilage repair

• US 9,393,195 B2
• Filed: 05/21/2013
• Issued: 07/19/2016
• Est. Priority Date: 03/22/2002
• Status: Expired due to Term

• Current Assignee: Histogenics Corporation (Ocugen, Inc.), Takagi Industrial Company Limited
• Original Assignee: Histogenics Corporation (Ocugen, Inc.)
• Inventors: Mizuno, Shuichi, Kusanagi, Akihiko, Tarrant, Laurence J. B., Tokuno, Toshimasa, Smith, Robert Lane
• Primary Examiner(s): Ware, Debbie K
• Assistant Examiner(s): Srivastava, Kailash C
• Application Number:
  US13/899,024
• Publication Number:
  US 20130273121A1
• Time in Patent Office: 1,155 Days
• Field of Search: 424/93.7, 424/423, 424/400, 435/395, 435/177, 435/366, 435/404, 435/180, 514/17, 514/7.6
• US Class Current: 1/1
• CPC Class Codes: A61F 2/28 Bones joints A61F2/30
• CPC Class Codes: A61F 2310/00365 Proteins; Polypeptides; Degradation products thereof
• 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 35/32 Bones; Osteocytes; Osteoblasts; Tendons; Tenocytes; Teeth; Odontoblasts; Cartilage; Chondrocytes; Synovial membrane
• 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: A61L 2300/64 Animal cells
• CPC Class Codes: A61L 2430/06 for cartilage reconstruction, e.g. meniscus
• CPC Class Codes: A61L 27/24 Collagen
• CPC Class Codes: A61L 27/3633 Extracellular matrix [ECM]
• CPC Class Codes: A61L 27/38 containing added animal cells organs or tissue containing native cells A61L27/36
• CPC Class Codes: A61L 27/3817 Cartilage-forming cells, e.g. pre-chondrocytes
• CPC Class Codes: A61L 27/3843 Connective tissue
• CPC Class Codes: A61L 27/3852 Cartilage, e.g. meniscus
• 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: A61L 27/56 Porous materials, e.g. foams or sponges
• CPC Class Codes: C12N 2521/00 Culture process characterised by the use of hydrostatic pressure, flow or shear forces
• CPC Class Codes: C12N 2533/54 Collagen; Gelatin
• CPC Class Codes: C12N 5/0655 Chondrocytes; Cartilage

Abstract

Neo-cartilage constructs suitable for implantation into a joint cartilage lesion in situ and a method for repair and restoration of function of injured, traumatized, aged or diseased cartilage. The construct comprises at least chondrocytes incorporated into a support matrix processed according to the algorithm comprising variable hydrostatic or atmospheric pressure or non-pressure conditions, variable rate of perfusion, variable medium composition, variable temperature, variable cell density and variable time to which the chondrocytes are subjected.

Claims

1. A method for preparing a neo-cartilage construct, said method comprising the steps of:

providing a lyophilized acellular matrix comprising a plurality of pores;

seeding said acellular matrix with a plurality of chondrocytes; and

culturing said seeded matrix under conditions that comprise;

applying cyclic hydrostatic pressure from about 0.5 MPa to about 3 MPa above atmospheric pressure, at a frequency of about 0.1 Hz to about 2.0 Hz, for about 6 days to about 14 days followed with a resting period at atmospheric pressure for about 7 days to about 28 days; and

said neo-cartilage construct is obtained.

2. The method of claim 1, wherein the acellular matrix further comprises at least one bioactive agent selected from the group consisting of a growth factor, a cytokine, a peptide, and a combination thereof.

3. The method of claim 1, further comprising the step of implanting said seeded matrix into a cartilage lesion of a subject.

4. The method of claim 3, wherein said chondrocytes are autologous or heterologous.

5. The method of claim 3, wherein a tissue sealant is used to implant the seeded matrix into the cartilage lesion in said subject.

6. The method of claim 5, wherein said tissue sealant is deposited into the cartilage lesion before the seeded matrix is implanted therein.

7. The method of claim 5, wherein said tissue sealant is deposited over the seeded matrix after implantation into the cartilage lesion in said subject.

8. The method of claim 5, wherein said tissue sealant is selected from the group consisting of gelatin, a copolymer of polyethylene glycol and poly-lactide or poly-glycolide, periodate-oxidized gelatin, 4-armed pentaerythritol thiol and a polyethylene glycol diacrylate, 4-armed tetra-succinimidyl ester or tetra-thiol derivatized PEG, photo-polymerizable polyethylene glycol-co-poly(α

-hydroxy acid)diacrylate macromer, 4-armed polyethylene glycol derivatized with succinimidyl ester and thiol further cross-linked with methylated collagen, derivatized polyethylene glycol (PEG), polyethylene glycol (PEG) cross-linked with alkylated collagen, tetra-hydrosuccinimidyl or tetra-thiol derivatized PEG, PEG cross-linked with methylated collagen, and a combination thereof.