Methods and compositions for repair of cartilage using an in vivo bioreactor

• US 8,298,560 B2
• Filed: 05/07/2010
• Issued: 10/30/2012
• Est. Priority Date: 02/07/2006
• Status: Active Grant

• Current Assignee: Spinalcyte LLC
• Original Assignee: Spinalcyte LLC
• Inventors: Sevrain, Lionel C., Verdier-Sevrain, Sylvie Y.
• Primary Examiner(s): DAVIS, RUTH A
• Application Number:
  US12/775,753
• Publication Number:
  US 20100285090A1
• Time in Patent Office: 907 Days
• Field of Search: 424/422
• US Class Current: 424/422
• CPC Class Codes: A61F 2/30756 Cartilage endoprostheses A61F2/3603 takes precedence
• CPC Class Codes: A61F 2/3099 for temporo-mandibular [TM, TMJ] joints endoprostheses for mandibular reconstruction A61F2/2803
• CPC Class Codes: A61F 2/32 for the hip
• CPC Class Codes: A61F 2/38 for elbows or knees
• CPC Class Codes: A61F 2/3804 for elbows
• CPC Class Codes: A61F 2/40 for shoulders
• CPC Class Codes: A61F 2/441 made of inflatable pockets or chambers filled with fluid, e.g. with hydrogel
• CPC Class Codes: A61F 2002/2817 Bone stimulation by chemical reactions or by osteogenic or biological products for enhancing ossification, e.g. by bone morphogenetic or morphogenic proteins [BMP] or by transforming growth factors [TGF]
• CPC Class Codes: A61F 2002/286 Bone stimulation by mechanical vibrations for enhancing ossification
• CPC Class Codes: A61F 2002/30062 (bio)absorbable, biodegradable, bioerodable, (bio)resorbable, resorptive
• CPC Class Codes: A61F 2002/30586 having two or more inflatable pockets or chambers
• CPC Class Codes: A61F 2002/30677 Means for introducing or releasing pharmaceutical products, e.g. antibiotics, into the body
• CPC Class Codes: A61F 2002/30762 Means for culturing cartilage
• CPC Class Codes: A61F 2002/30764 Cartilage harvest sites
• CPC Class Codes: A61F 2002/30766 Scaffolds for cartilage ingrowth and regeneration
• CPC Class Codes: A61F 2002/444 for replacing the nucleus pulposus
• CPC Class Codes: A61F 2002/4445 Means for culturing intervertebral disc tissue
• CPC Class Codes: A61F 2002/445 Intervertebral disc tissue harvest sites
• CPC Class Codes: A61F 2002/4635 using minimally invasive surgery
• CPC Class Codes: A61F 2210/0004 bioabsorbable
• 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 35/33 : Fibroblasts
• CPC Class Codes: A61K 38/18 : Growth factors; Growth regulators
• CPC Class Codes: A61K 45/06 : Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61L 2430/06 : for cartilage reconstruction, e.g. meniscus
• CPC Class Codes: A61L 27/3817 : Cartilage-forming cells, e.g. pre-chondrocytes
• 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: A61P 19/00 : Drugs for skeletal disorders
• CPC Class Codes: A61P 19/04 : for non-specific disorders of the connective tissue
• CPC Class Codes: A61P 31/04 : Antibacterial agents
• CPC Class Codes: A61P 31/10 : Antimycotics
• CPC Class Codes: A61P 31/12 : Antivirals
• CPC Class Codes: A61P 41/00 : Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C12N 2500/02 : Atmosphere, e.g. low oxygen conditions
• CPC Class Codes: C12N 2500/38 : Vitamins
• CPC Class Codes: C12N 2501/155 : Bone morphogenic proteins [BMP]; Osteogenins; Osteogenic factor; Bone inducing factor
• CPC Class Codes: C12N 2506/1307 : from adult fibroblasts
• CPC Class Codes: C12N 2521/00 : Culture process characterised by the use of hydrostatic pressure, flow or shear forces
• CPC Class Codes: C12N 2533/74 : Alginate
• CPC Class Codes: C12N 5/0655 : Chondrocytes; Cartilage

Abstract

Methods and compositions for the biological repair of cartilage using a hybrid construct combining both an inert structure and living core are described. The inert structure is intended to act not only as a delivery system to feed and grow a living core component, but also as an inducer of cell differentiation. The inert structure comprises concentric internal and external and inflatable/expandable balloon-like bio-polymers. The living core comprises the cell-matrix construct comprised of HDFs, for example, seeded in a scaffold. The method comprises surgically removing a damaged cartilage from a patient and inserting the hybrid construct into the cavity generated after the foregoing surgical intervention. The balloons of the inert structure are successively inflated within the target area, such as a joint, for example. Also disclosed herein are methods for growing and differentiating human fibroblasts into chondrocyte-like cells via mechanical strain.

Claims

1. An implantable device, comprising:

a cells/scaffold composition encapsulated inside a membrane, said membrane having an inside and an outside; and

a structure for exchanging at least part of fluid that is inside the membrane,

wherein the membrane has the following characteristics;

semi-permeable;

biocompatible;

biodegradable; and

resorbable.

2. The device of claim 1, wherein the scaffold is comprised of a synthetic polymer, a natural hydrogel, or a synthetic hydrogel.

3. The device of claim 2, wherein the synthetic polymer is polyglycolic acid, polylactic acid, polylactic-co-glycolic acid, poly-ε

-caprolactone, or poly(glycerol-Sebacate) (PGS).

4. The device of claim 2, wherein the synthetic polymer is a polyphosphazene, a polyanhydride, or a poly(orthoester).

5. The device of claim 2, wherein the natural hydrogel comprises collagen, hyaluronic acid, alginate, agarose, chitosan, fibrin, gelatin, or a copolymer thereof.

6. The device of claim 2, wherein the synthetic hydrogel comprises poly(ethylene oxide), poly(vinyl alcohol), poly(acrylic acid), poly(propylene fumarate-co-ethylene glycol), or a copolymer thereof.

7. The device of claim 1, wherein the cells are chondrocyte cells or chondrocyte-like cells.

8. The device of claim 7, wherein the chondrocyte cells or chondrocyte-like cells secrete a molecule selected from the group consisting of aggrecan, type II collagen, Sox-9 protein, cartilage link protein, and perlecan.

9. The device of claim 1, wherein the cells were differentiated from fibroblast cells and/or stem cells.

10. The device of claim 9, wherein the fibroblast cells are dermal fibroblasts, tendon fibroblasts, ligament fibroblasts, synovial fibroblasts, foreskin fibroblasts, or a mixture thereof.

11. The device of claim 1, wherein the membrane is comprised of a biodegradable, biocompatible, and resorbable polymer.

12. The device of claim 1, wherein the membrane is comprised of a polyacrylate, a polyvinylidene, a polyvinyl chloride copolymer, a polyurethane, a polystyrene, a polyamide, a cellulose acetate, a cellulose nitrate, a polysulfone, a polyphosphazene, a polyacrylonitrile, a poly(acrylonitrile/covinyl chloride) or a derivative, copolymer or mixture thereof.

13. The device of claim 1, wherein the membrane is generated by polyelectrolyte complexation.

14. The device of claim 1, wherein the membrane is comprised of polyglycolic acid (PGA), polylactic acid (PLA), polylactic-co-glycolic acid (PLGA), poly-ε

-caprolactone (PCL), polyurethane (PU), polydioxanone (PDO), a polyethylene, poly (glycerol sebacate) (PGS), or a derivative, copolymer, or mixture thereof.