Solid forms for tissue repair

• US 8,808,725 B2
• Filed: 11/19/2009
• Issued: 08/19/2014
• Est. Priority Date: 11/20/2008
• Status: Active Grant

• Current Assignee: CartiHeal (2009) Ltd. (Smith & Nephew PLC)
• Original Assignee: CartiHeal (2009) Ltd. (Smith & Nephew PLC)
• Inventors: Altschuler, Nir, Vago, Razi
• Primary Examiner(s): Krass, Frederick
• Assistant Examiner(s): LIU, TRACY
• Application Number:
  US13/130,272
• Publication Number:
  US 20110256228A1
• Time in Patent Office: 1,734 Days
• Field of Search: 424/423, 424/400, 424/93.7
• US Class Current: 424/423
• CPC Class Codes: A61F 2/28 Bones joints A61F2/30
• CPC Class Codes: A61F 2/30 Joints
• CPC Class Codes: A61F 2/30756 Cartilage endoprostheses A61F2/3603 takes precedence
• CPC Class Codes: A61F 2/4618 of cartilage
• CPC Class Codes: A61F 2002/30205 conical
• CPC Class Codes: A61F 2002/30224 cylindrical
• CPC Class Codes: A61F 2002/30299 umbrella-shaped or mushroom-shaped
• CPC Class Codes: A61F 2002/30795 Blind bores, e.g. of circular cross-section
• CPC Class Codes: A61F 2002/30878 with non-sharp protrusions, for instance contacting the bone for anchoring, e.g. keels, pegs, pins, posts, shanks, stems, struts
• CPC Class Codes: A61F 2002/30891 Plurality of protrusions
• CPC Class Codes: A61F 2002/4627 with linear motion along or rotating motion about the instrument axis or the implantation direction, e.g. telescopic, along a guiding rod, screwing inside the instrument
• CPC Class Codes: A61F 2230/0067 conical
• CPC Class Codes: A61F 2230/0069 cylindrical
• CPC Class Codes: A61F 2230/0093 Umbrella-shaped, e.g. mushroom-shaped
• CPC Class Codes: A61F 2310/00341 Coral, e.g. aragonite, porite
• CPC Class Codes: A61K 33/10 Carbonates; Bicarbonates
• 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 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61L 2300/10 containing or releasing inorganic materials
• CPC Class Codes: A61L 2300/406 : Antibiotics
• CPC Class Codes: A61L 2300/414 : Growth factors
• CPC Class Codes: A61L 2300/426 : Immunomodulating agents, i.e. cytokines, interleukins, interferons
• CPC Class Codes: A61L 2300/606 : Coatings
• CPC Class Codes: A61L 2300/64 : Animal cells
• CPC Class Codes: A61L 2430/02 : for reconstruction of bones; weight-bearing implants
• CPC Class Codes: A61L 2430/06 : for cartilage reconstruction, e.g. meniscus
• CPC Class Codes: A61L 27/025 : Other specific inorganic materials not covered by A61L27/04 - A61L27/12
• CPC Class Codes: A61L 27/34 : Macromolecular materials
• CPC Class Codes: A61L 27/3604 : characterised by the human or animal origin of the biological material, e.g. hair, fascia, fish scales, silk, shellac, pericardium, pleura, renal tissue, amniotic membrane, parenchymal tissue, fetal tissue, muscle tissue, fat tissue, enamel
• CPC Class Codes: A61L 27/365 : Bones
• CPC Class Codes: A61L 27/3654 : Cartilage, e.g. meniscus
• 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 27/3821 : Bone-forming cells, e.g. osteoblasts, osteocytes, osteoprogenitor cells
• CPC Class Codes: A61L 27/3834 : Cells able to produce different cell types, e.g. hematopoietic stem cells, mesenchymal stem cells, marrow stromal cells, embryonic stem cells
• CPC Class Codes: A61L 27/3847 : Bones
• CPC Class Codes: A61L 27/3852 : Cartilage, e.g. meniscus
• CPC Class Codes: A61L 27/427 : of other specific inorganic materials not covered by A61L27/422 or A61L27/425
• CPC Class Codes: A61L 27/446 : with other specific inorganic fillers other than those covered by A61L27/443 or A61L27/46
• 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: A61P 19/00 : Drugs for skeletal disorders
• CPC Class Codes: A61P 19/02 : for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 19/04 : for non-specific disorders of the connective tissue
• CPC Class Codes: A61P 19/08 : for bone diseases, e.g. rachitism, Paget's disease
• CPC Class Codes: C08L 5/08 : Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof

Abstract

This invention provides coral-based scaffolds for cartilage repair, and instruments for insertion and utilization of same within a site of cartilage repair.

Claims

1. A scaffold for repair of cartilage or an osteochondral defect, said scaffold comprising coral having at least a first portion of an exposed surface, which first portion is raised with respect to at least a second portion of said exposed surface in said coral, wherein said at least a first portion of said coral is proximal to a hollow or hollows along a longitudinal axis of said first portion and wherein said at least a second portion abuts said hollow or hollows and wherein said first portion comprises at least a region, which specifically positions and confines said coral within a site of cartilage repair.

2. The scaffold of claim 1, wherein said coral comprises a polymer coating.

3. The scaffold of claim 2, wherein said polymer coating is permeable.

4. The scaffold of claim 2, wherein said polymer coating is discontinuous and optionally in the form of aggregates or particles.

5. The scaffold of claim 2, wherein said polymer comprises a natural polymer comprising collagen, elastin, silk, hyaluronic acid, chitosan, and any combinations thereof.

6. The scaffold of claim 5, wherein said collagen or hyaluronic acid is cross-linked.

7. The scaffold of claim 1, wherein said scaffold comprises a cytokine, a bone morphogenetic protein (BMP), a chelator, a cell population, a therapeutic compound, or an antibiotic, or any combination thereof.

8. The scaffold of claim 7, wherein said coral is seeded with a cell population and wherein said cell population comprises mesenchymal stem cells or osteoblasts or chondrocytes or other cells involved in cartilage repair or a combination thereof.

9. The scaffold of claim 7, wherein said therapeutic compound comprises an anti-inflammatory compound, an anti-infective compound, a growth factor, a pro-angiogenic factors or a combination thereof.

10. The scaffold of claim 1, wherein the scaffold comprises a shape comprising a cone, a tack, a screw, a cylinder, a rectangular bar, a plate, a disc, a pyramid, a granule, a ball or a cube.

11. The scaffold of claim 1, wherein at least a portion of said scaffold penetrates through a bone, resulting in said portion inserting within a bone marrow proximal to a site of cartilage or osteochondral repair.

12. A method of inducing or enhancing cartilage repair, said method comprising implanting in a subject, a scaffold of claim 1 within a site of cartilage repair in said subject, wherein a region of said scaffold penetrates through a bone, resulting in said region inserting within a bone marrow, proximal to said site of cartilage repair in said subject.

13. The method of claim 12, wherein said subject is afflicted with a cartilage defect or disorder wherein said cartilage defect or disorder comprises a full or partial thickness articular cartilage defect, osteoarthritis, osteochondritis, avascular necrosis, a joint defect or a defect resulting from trauma, sports, diseases or repetitive stress.

14. A method of treating an osteochondral defect in a subject, said method comprising implanting in a subject, a scaffold of claim 1 within a site of osteochondral defect in said subject, wherein a region of said scaffold penetrates through a bone, resulting in said region inserting within a bone marrow, proximal to said site of osteochondral defect in said subject.

25. The scaffold of claim 1, wherein said scaffold lacks a polymer coating.

26. The scaffold of claim 1, wherein the hollow or hollows increase the exposed surface area of the scaffold.

15. A scaffold for tissue repair, said scaffold comprising a polymer form enveloping coral particles, wherein said scaffold is rigid and has at least a first portion of an exposed surface, which first portion is raised with respect to at least a second portion of said exposed surface in said coral, wherein said at least a first portion of said coral is proximal to a hollow or hollows along a longitudinal axis of said first portion and wherein said at least a second portion abuts said hollow or hollows and wherein said first portion comprises at least a region, which specifically positions and confines said coral within a site of cartilage repair.

16. The scaffold of claim 15, wherein said polymer comprises a natural polymer comprising collagen, elastin, silk, hyaluronic acid, chitosan, and any combinations thereof.

17. The scaffold of claim 15, wherein said polymer form is flexible.

18. The scaffold of claim 15, wherein said polymer enhances cartilage or bone formation or repair.

19. The scaffold of claim 15, wherein said coral particles are micronized to 1-10 μ

m or 5-20 μ

m or 10-50 μ

m in size.

20. The scaffold of claim 15, wherein said polymer is permeable.

21. The scaffold of claim 15, wherein said scaffold comprises an anti-inflammatory compound, an anti-infective compound, a growth factor, a pro-angiogenic factor or a combination thereof.

22. The scaffold of claim 15, comprising a pasting agent.

23. The scaffold of claim 22, wherein said pasting agent comprises a native or cross linked hyaluronan (HA), collagen or fibrinogen.

24. The scaffold of claim 15, wherein said scaffold comprises a cytokine, a bone morphogenetic protein (BMP), a chelator, a cell population, a therapeutic compound, or an antibiotic, or any combination thereof.