Porous delivery scaffold and method

• US 7,201,917 B2
• Filed: 07/15/2002
• Issued: 04/10/2007
• Est. Priority Date: 07/16/2001
• Status: Expired due to Term

• Current Assignee: DePuy Synthes Products LLC (Johnson & Johnson)
• Original Assignee: Depuy Products Incorporated (Johnson & Johnson)
• Inventors: Schwartz, Herbert E., Malaviya, Prasanna, Plouhar, Pamela L., Orban, Janine M.
• Primary Examiner(s): Tate; Christopher
• Assistant Examiner(s): Srivastava; Kailash C.
• Application Number:
  US10/195,633
• Publication Number:
  US 20030049299A1
• Time in Patent Office: 1,730 Days
• Field of Search: 424/424, 424/423, 435/244, 435/245, 435/378, 435/398, 435/408, 435/325, 426/384
• US Class Current: 424/423
• CPC Class Codes: A61B 17/064 Surgical staples, i.e. penetrating the tissue
• CPC Class Codes: A61B 17/0642 for bones, e.g. for osteosynthesis or connecting tendon to bone
• CPC Class Codes: A61B 2017/0646 for insertion into cartillege, e.g. meniscus
• CPC Class Codes: A61F 2/0063 Implantable repair or support meshes, e.g. hernia meshes
• CPC Class Codes: A61F 2/0811 Fixation devices for tendons or ligaments
• CPC Class Codes: A61F 2/30749 Fixation appliances for connecting prostheses to the body
• CPC Class Codes: A61F 2/3872 Meniscus for implantation between the natural bone surfaces
• CPC Class Codes: A61F 2002/30294 Conical or frustoconical body made by spirally rolling up a sheet or a strip around itself
• CPC Class Codes: A61F 2002/30751 for attaching cartilage scaffolds to underlying bone
• CPC Class Codes: A61F 2002/30766 Scaffolds for cartilage ingrowth and regeneration
• CPC Class Codes: A61F 2230/0091 helically-coiled or spirally-coiled, i.e. having a 2-D spiral cross-section
• CPC Class Codes: A61L 2300/252 Polypeptides, proteins, e.g. glycoproteins, lipoproteins, cytokines
• CPC Class Codes: A61L 2300/412 Tissue-regenerating or healing or proliferative agents
• CPC Class Codes: A61L 2300/602 Type of release, e.g. controlled, sustained, slow
• CPC Class Codes: A61L 2300/64 Animal cells
• CPC Class Codes: A61L 2430/06 for cartilage reconstruction, e.g. meniscus
• CPC Class Codes: A61L 27/18 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• 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 27/3633 Extracellular matrix [ECM]
• CPC Class Codes: A61L 27/3687 characterised by the use of chemical agents in the treatment, e.g. specific enzymes, detergents, capping agents, crosslinkers, anticalcification agents
• CPC Class Codes: A61L 27/3691 : characterised by physical conditions of the treatment, e.g. applying a compressive force to the composition, pressure cycles, ultrasonic/sonication or microwave treatment, lyophilisation
• CPC Class Codes: A61L 27/3843 : Connective tissue
• 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: A61L 31/005 : Ingredients of undetermined constitution or reaction products thereof
• CPC Class Codes: C08L 67/04 : Polyesters derived from hydroxycarboxylic acids, e.g. lactones C08L67/06 takes precedence

Abstract

A method of making an implantable scaffold for repairing damaged or diseased tissue includes the step of suspending pieces of an extracellular matrix material in a liquid. The extracellular matrix material and the liquid are formed into a mass. The liquid is subsequently driven off so as to form interstices in the mass. The scaffold may further comprise biological agents that promote tissue repair and healing. Porous implantable scaffolds fabricated by such a method are also disclosed.

Claims

1. A method of making an implantable scaffold for repairing or regenerating body tissue, the method comprising the steps of:

comminuting naturally occurring extracellular matrix material in the presence of a liquid to form a slurry comprising intertwined, ribbon-like, cohesive pieces of the naturally occurring extracellular matrix material suspended in the liquid;

freeze-drying the intertwined, ribbon-like, cohesive pieces of naturally occurring extracellular matrix material and the liquid to form a porous structure; and

incorporating at least one biological agent into the freeze-dried extracellular matrix material.

2. The method of claim 1, further comprising the step of freezing the extracellular matrix material and the liquid to form ice crystals from the liquid, the freezing step being performed prior to the freeze drying step.

3. The method of claim 2, wherein the freeze drying step further comprises subliming the ice crystals directly to vapor in the presence of a vacuum.

4. The method of claim 1, wherein the freeze-drying step comprises subliming the liquid so as to form a porous body.

5. The method of claim 1, wherein the extracellular matrix material comprises material selected from the group consisting of:

small intestine sub-mucosa, bladder sub-mucosa, stomach sub-mucosa, alimentary sub-mucosa, respiratory sub-mucosa, genital sub-mucosa, and liver basement membrane.

6. The method of claim 1, further comprising the step of flash-freezing the extracellular matrix material and the liquid prior to the freeze-drying step.

7. The method of claim 1, further comprising the step of compacting the pieces of naturally occurring extracellular matrix material prior to the freeze drying step.

8. The method of claim 1, further comprising the step of centrifuging the pieces of naturally occurring extracellular matrix material prior to the freeze drying step.

9. The method of claim 1, further comprising the step of freezing the naturally occurring extracellular matrix material and the liquid at a controlled rate of temperature drop.

10. The method of claim 9, wherein the freezing step comprises varying the rate of temperature drop so as to vary the pore size of the scaffold.

11. The method of claim 1, wherein the incorporating step comprises:

incubating the freeze dried extracellular matrix material with a solution comprising at least one biological agent; and

cross-linking the freeze-dried extracellular matrix material.

12. The method of claim 11, wherein cross-linking the freeze-dried extracellular matrix material comprises cross-linking the freeze-dried extracellular matrix material by use of a water-soluble carbodiimide.

13. The method of claim 11, wherein cross-linking the freeze-dried extracellular matrix material comprises cross-linking the freeze-dried extracellular matrix material by use of transglutaminase.

14. The method of claim 1, wherein the incorporating step comprises covalently attaching the biological agent to the extracellular matrix material.

15. The method of claim 1, wherein the biological agent is selected from the group consisting of a bioactive agent, a biologically derived agent, and a cell.