Three dimensional cell protector/pore architecture formation for bone and tissue constructs

• US 7,713,542 B2
• Filed: 05/18/2005
• Issued: 05/11/2010
• Est. Priority Date: 01/14/2005
• Status: Expired due to Fees

• Current Assignee: ADA Foundation
• Original Assignee: ADA Foundation
• Inventors: Weir, Michael D., Xu, Huakun
• Primary Examiner(s): Ford; Allison M
• Application Number:
  US11/132,028
• Publication Number:
  US 20060159717A1
• Time in Patent Office: 1,819 Days
• Field of Search: None
• US Class Current: 424/426
• CPC Class Codes: A61K 38/1825 Fibroblast growth factor [FGF]
• CPC Class Codes: A61K 38/1841 Transforming growth factor [TGF]
• CPC Class Codes: A61K 38/1858 Platelet-derived growth factor [PDGF]
• CPC Class Codes: A61K 38/1875 Bone morphogenic factor; Osteogenins; Osteogenic factor; Bone-inducing factor
• CPC Class Codes: A61L 2400/06 Flowable or injectable implant compositions
• CPC Class Codes: A61L 2430/02 for reconstruction of bones; weight-bearing implants
• CPC Class Codes: A61L 27/20 Polysaccharides
• CPC Class Codes: A61L 27/38 containing added animal cells organs or tissue containing native cells A61L27/36
• CPC Class Codes: A61L 27/425 of phosphorus containing material, e.g. apatite
• CPC Class Codes: A61L 27/46 with phosphorus-containing inorganic fillers
• CPC Class Codes: A61L 27/58 Materials at least partially resorbable by the body
• 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 5/04 Alginic acid; Derivatives thereof
• CPC Class Codes: C08L 5/08 Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof
• CPC Class Codes: C08L 67/04 Polyesters derived from hydroxycarboxylic acids, e.g. lactones C08L67/06 takes precedence
• CPC Class Codes: C08L 89/06 derived from leather or skin , e.g. gelatin

Abstract

Living cellular material is encapsulated or placed in a protective material (cell protector) which is biocompatible, biodegradable and has a three-dimensional form. The three dimensional form is incorporated into a matrix that maybe implanted in vivo, ultimately degrade and thereby by replaced by living cell generated material.

Claims

1. A moldable implant material for implantation of living cells, comprising:

(a) at least one living cell;

(b) a cell protector material, characterized in that the cell protector material is biocompatible with said at least one living cell, biodegradable in situ subsequent to implantation,-in the form of rods or tubes having a diameter in the range of about 0.001 mm to 10 mm and a length in the range of about 10 mm to 1 mm, and the rods or tubes interconnect to form a three-dimensional, interconnected structure; and

(c) a matrix material, characterized in that the matrix material is, at least in part, biocompatible in vivo, hardenable in situ subsequent to implantation, and comprises a calcium and phosphorous compound selected from the group consisting of tetracalcium phosphate (Ca₄[PO₄]₂O, TTCP) based self-hardening calcium phosphate cements, alpha-tricalcium phosphate (alpha-TCP, α

-Ca₃[PO₄]₂) based self-hardening calcium phosphate cements, beta-tricalcium phosphate (beta-TCP, β

-Ca₃[PO₄]₂) based self-hardening calcium phosphate cements, dicalcium phosphate anhydrous (DCPA, CaHPO₄) based self-hardening calcium phosphate cements, dicalcium phosphate dihydrate (DCPD, CaHPO₄·

2H₂O) based self-hardening calcium phosphate materials, amorphous calcium phosphate-based self-hardening, calcium phosphate materials, and combinations thereof;

wherein the cell protector material substantially encapsulates the at least one living cell; and

wherein the cell protector material, comprising the at least one living cell, is contained, at least in part, within the matrix material.

2. The moldable implant material of claim 1, wherein the matrix material is, at least in part, biodegradable.

3. The moldable implant material of claim 2, wherein the cell protector material has a faster biodegradation rate in situ than the matrix material.

4. The moldable implant material of claim 1, wherein the at least one living cell is selected from the group consisting of osteoblasts, osteoclasts, bone cells, mesenchyinal stem cells, fibroblasts, chondrocytes, odontoblasts, endothelial cells, progenitor cells, stem cells, and combinations thereof.

5. The moldable implant material of claim 1 wherein the at least one living cell is selected from the group consisting of bone cells and progenitors of bone cells.

6. The moldable implant material of claim 1, wherein the cell protector material comprises a material selected from the group consisting of biodegradable or resorbable ceramics, organic materials, inorganic materials, and combinations thereof.

7. The moldable implant material of claim 6, wherein the cell protector material comprises an organic Material.

8. The moldable implant material of claim 1 wherein the cell protector material comprises about 5% to about 95% by volume of the implant material.

9. The moldable implant material of claim 1 wherein the cell protector material comprises about 20% to about 80% by volume of the implant material

10. The moldable implant material of claim 1 wherein the cell protector material comprises about 30% to about 70% by volume of the implant material

11. The moldable implant material of claim 1, wherein the matrix material comprises two species of calcium and phosphorous compounds selected from the group consisting of tetracalcium phosphate (Ca₄[PO₄]₂O, TTCP) based self hardening calcium phosphate cements, alpha-tricalcium phosphate (alpha-TCP, α

-Ca₃[PO₄]₂) based self hardening calcium phosphate cements, beta-tricalcium phosphate (beta-TCP, β

-Ca₃[PO₄]₂) based self hardening calcium phosphate cements, dicalcium phosphate anhydrous (DCPA, CaHPO₄) based self hardening calcium phosphate cements, dicalcium phosphate dihydrate (DCPD, CaHPO₄ ·

2H₂O) based self hardening calcium phosphate materials, amorphous calcium phosphate-based self-hardening, calcium phosphate materials, and combinations thereof.

12. The moldable implant material of claim 1, wherein the matrix material is comprised of a carrier material which is hardenable in situ subsequent to implantation.

13. The moldable implant material of claim 1 wherein the matrix material is, at least in part, not biodegradable.

14. The moldable implant material of claim 1, further comprising (d) a cell nutrient material.

15. The moldable implant material of claim 1, wherein t he implant material is in the form of a plastic paste.