Articular cartilage repair

• US 10,022,231 B2
• Filed: 10/07/2016
• Issued: 07/17/2018
• Est. Priority Date: 07/22/2016
• Status: Active Grant

• Current Assignee: Cytex Therapeutics, Inc.
• Original Assignee: Cytex Therapeutics, Inc.
• Inventors: Estes, Bradley T., Guilak, Farshid, Moutos, Franklin Thomas
• Primary Examiner(s): Snow, Bruce E
• Assistant Examiner(s): HOBAN, MELISSA A
• Application Number:
  US15/288,312
• Publication Number:
  US 20180021138A1
• Time in Patent Office: 648 Days
• 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 2002/30062 (bio)absorbable, biodegradable, bioerodable, (bio)resorbable, resorptive
• CPC Class Codes: A61F 2002/30448 using adhesives
• CPC Class Codes: A61F 2002/30757 made of a sheet covering the natural articular surface, e.g. cap
• CPC Class Codes: A61F 2002/30766 Scaffolds for cartilage ingrowth and regeneration
• CPC Class Codes: A61F 2002/3092 having an open-celled or open-pored structure
• CPC Class Codes: A61F 2002/30985 using three dimensional printing [3DP]
• CPC Class Codes: A61L 2300/258 Genetic materials, DNA, RNA, genes, vectors, e.g. plasmids
• CPC Class Codes: A61L 2300/414 Growth factors
• 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 27/18 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 27/30 Inorganic materials
• CPC Class Codes: A61L 27/38 containing added animal cells organs or tissue containing native cells A61L27/36
• CPC Class Codes: A61L 27/3852 Cartilage, e.g. meniscus
• 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 19/08 for bone diseases, e.g. rachitism, Paget's disease

Abstract

An implant is configured for repair and regeneration of cartilage lesions. The implant includes a three-dimensional woven textile scaffold and a three-dimensional rigid, porous substrate. The scaffold is bonded to the substrate such that the substrate supports the scaffold. The substrate is configured to be inserted into bone tissue including cartilage lesions such that the substrate and the scaffold replace the bone tissue including the cartilage lesions. The substrate and scaffold are further configured such that after the substrate and the scaffold have replaced the bone tissue including the cartilage lesions, the substrate and scaffold promote growth and integration of new bone tissue into the implant.

Claims

1. A cartilage repair implant for repair and regeneration of a cartilage lesion, the implant comprising:

a three-dimensional scaffold comprising at least three layers of woven fibers; and

a three-dimensional porous substrate fixedly coupled to the scaffold and configured to press fit and integrate into bone, wherein,

the three-dimensional porous substrate comprises a first three-dimensionally printed layer and a second three-dimensionally printed layer arranged on top of the first three-dimensionally printed layer,

the first three-dimensionally printed layer includes a first plurality of extruded struts oriented in a first strut direction,

the second three-dimensionally printed layer includes a second plurality of extruded struts oriented in a second strut direction, and

the second strut direction is angled approximately 30 degrees to approximately 120 degrees relative to the first strut direction.

2. The cartilage repair implant of claim 1, wherein:

the at least three layers of woven fibers includes;

in-plane warp fibers oriented in a first direction;

weft fibers oriented in a second direction orthogonal to the first direction; and

binding fibers oriented in a third direction orthogonal to the first and second directions, and

the weft fibers and the binding fibers are arranged between the in-plane warp fibers.

3. The cartilage repair implant of claim 1, wherein the three-dimensional scaffold is a three-dimensional warp interlock fabric.

4. The cartilage repair implant of claim 1, wherein:

the at least three layers of woven fibers includes;

a warp layer comprising in-plane warp fibers oriented in a first direction;

a weft layer comprising weft fibers oriented in a second direction orthogonal to the first direction; and

a binding layer comprising binding fibers oriented in a third direction orthogonal to the first and second directions, and

the three-dimensional scaffold includes five warp layers and six weft layers interconnected by fibers oriented in the third direction.

5. The cartilage repair implant of claim 1, wherein:

the at least three layers of woven fibers includes;

a warp layer comprising in-plane warp fibers oriented in a first direction;

a weft layer comprising weft fibers oriented in a second direction orthogonal to the first direction; and

a binding layer comprising binding fibers oriented in a third direction orthogonal to the first and second directions, and

the three-dimensional scaffold includes twenty-four yarns per centimeter in each of the warp layers, fifteen to twenty yarns per centimeter in each of the weft layers and twenty-four yarns per centimeter oriented in the third direction.

6. The cartilage repair implant of claim 1, wherein at least one of the three-dimensional scaffold and the three-dimensional substrate has a void volume of at least 50%.

7. The cartilage repair implant of claim 1, wherein a compressive modulus of the three-dimensional scaffold is between approximately 200 kPa and approximately 5 MPa.

8. The cartilage repair implant of claim 1, wherein each of said first and second plurality of extruded struts has a diameter of approximately 150 μ

m to approximately 500 μ

m.

9. The cartilage repair implant of claim 1, wherein:

at least a portion of at least one of the three-dimensional scaffold and the three-dimensional porous substrate is coated with at least one biological agent, and

the at least one biological agent is selected from the group consisting of collagen, hyaluronic acid, alginate, agarose, chitosan, gelatin, laminin, fibronectin, fibrin, proteoglycan, cartilage oligomeric matrix protein, hyaluronic acid, collagen type I, collagen type II, peptide sequences, self-assembling peptides, anti-inflammatory drugs, bone morphogenetic proteins and other cytokines, cytokines inhibitors, cartilage-derived matrix, demineralized bone matrix and/or other decellularized extracellular matrix-derived tissues.

10. The cartilage repair implant of claim 1, wherein:

at least a portion of the woven fibers are coated with at least one inorganic matrix, and

the at least one inorganic matrix is selected from the group consisting of hydroxyapatite, calcium phosphate, calcium carbonate, alumina, zirconia, yttria-stabilized zirconia, silicon nitride-based materials, bioactive glass, and/or glass ceramics.

11. The cartilage repair implant of claim 1, wherein:

at least a portion of the three-dimensional scaffold is at least partially filled with a biomaterial gel, and

the biomaterial gel is selected from the group consisting of collagen, hyaluronic acid, alginate, agarose, chitosan, gelatin, laminin, fibronectin, interpenetrating networks containing fully biologic materials, fully synthetic, or mixtures thereof and/or fibrin or combinations thereof.

12. The cartilage repair implant of claim 1, wherein at least a portion of the woven fibers are coated with virus, plasmids, or DNA adapted to transfect or transduce cells within the implant for cartilage and/or bone induction.

13. The cartilage repair implant of claim 1, further comprising:

at least one cell embedded within at least one of the three-dimensional scaffold and the three-dimensional porous substrate, wherein;

the at least one cell is selected from the group consisting of primary cells, undifferentiated progenitor cells, stem cells, induced pluripotent stem cells and combinations thereof,

the undifferentiated progenitor cells or stem cells are selected from the group consisting of stem or progenitor cells derived from adipose tissue, bone marrow, synovium, muscle, bone, cord blood, periosteum, and combinations thereof, and

the primary cells are selected from the group consisting of chondrocytes, osteoblasts, fibroblasts, fibrochondrocytes, and combinations thereof.

14. The cartilage repair implant of claim 1, wherein:

each of the woven fibers and the three-dimensional porous substrate are formed of a biocompatible material, and

the biocompatible material is selected from the group consisting of an absorbable material, a non-absorbable material, and combinations thereof, wherein;

the non-absorbable material is selected from the group consisting of a polytetrafluoroethylene (PTFE), an expanded PTFE (ePTFE), a polyamide, a nylon, a polysulfone, a cellulosic, an acrylic, polyvinyl alcohol, carbon, ceramic, a metal, an acrylic, a polycarbonate, a polyester, a polyether, a poly(ether ketone), a poly(ether ether ketone), a poly(ethylene terephthalate), a poly(methyl(meth)acrylate), a polyolefin, a polysulfone, a polyurethane, and

the absorbable material is selected from the group consisting of a polyglycolic acid (PGA), a polylactic acid (PLA), a polyglycolide-lactide, a polycaprolactone, a polydioxanone, a polyoxalate, a polyanhydride, a poly(phosphoester), catgut suture, collagen, silk, alginate, agarose, chitin, chitosan, hydroxyapatite, bioabsorbable calcium phosphate, hyaluronic acid, elastin, a polyorthoester, a poly(amino acid), a pluronic/F-12, a poly(ethylene oxide)/poly(ethylene glycol) (PEO/PEG), collagen, gelatin, fibrin, hyaluronic acid, a proteoglycan, elastin, and combinations thereof.

15. The cartilage repair implant of claim 1, wherein:

a plurality of interstices are formed within the three-dimensional scaffold, and

each of the interstices defines a pore size of approximately 50 μ

m to approximately 1,000 μ

m.

16. The cartilage repair implant of claim 15, wherein each of the interstices defines a pore size of approximately 100 μ

m to approximately 500 μ

m.

17. The cartilage repair implant of claim 1, wherein the three-dimensional scaffold is formed by a plurality of elements, each element of the plurality of elements having a diameter of approximately 25 μ

m to approximately 300 μ

m.

18. The cartilage repair implant of claim 17, wherein each element of the plurality of elements has a diameter of approximately 50 μ

m to approximately 200 μ

m.

19. The cartilage repair implant of claim 17, wherein each of said first and second plurality of extruded struts of the three-dimensional porous substrate has a diameter of approximately 50 μ

m to approximately 200 μ

m.

20. The cartilage repair implant of claim 1, wherein each of said first and second plurality of extruded struts of the three-dimensional porous substrate has a diameter of approximately 25 μ

m to approximately 300 μ

m.