Tissue-derived tissuegenic implants, and methods of fabricating and using same

• US 8,883,210 B1
• Filed: 05/16/2011
• Issued: 11/11/2014
• Est. Priority Date: 05/14/2010
• Status: Active Grant

• Current Assignee: Musculoskeletal Transplant Foundation
• Original Assignee: Musculoskeletal Transplant Foundation
• Inventors: Truncale, Katherine Gomes, Gertzman, Arthur A., Huang, Yen-Chen, Semler, Eric, Chnari, Evangelia, Dasgupta, Anouska, Yannariello-Brown, Judith, Riley, Terri
• Primary Examiner(s): BERTOGLIO, VALARIE E
• Application Number:
  US13/108,856
• Time in Patent Office: 1,275 Days
• Field of Search: None
• US Class Current: 424/484
• 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 38/1825 Fibroblast growth factor [FGF]
• CPC Class Codes: A61K 38/1841 Transforming growth factor [TGF]
• CPC Class Codes: A61K 38/19 Cytokines; Lymphokines; Interferons
• CPC Class Codes: C12N 2501/155 Bone morphogenic proteins [BMP]; Osteogenins; Osteogenic factor; Bone inducing factor
• CPC Class Codes: C12N 2533/90 Substrates of biological origin, e.g. extracellular matrix, decellularised tissue
• CPC Class Codes: C12N 5/0605 Cells from extra-embryonic tissues, e.g. placenta, amnion, yolk sac, Wharton's jelly
• CPC Class Codes: C12N 5/0653 Adipocytes; Adipose tissue
• CPC Class Codes: C12N 5/0654 Osteocytes, Osteoblasts, Odontocytes; Bones, Teeth
• CPC Class Codes: C12N 5/0667 Adipose-derived stem cells [ADSC]; Adipose stromal stem cells
• CPC Class Codes: C12N 5/0668 Mesenchymal stem cells from other natural sources

Abstract

The disclosure provides implants containing a plurality of particles containing at least one population of viable tissuegenic cells adherent to and resident in the growth-conductive matrix or at least viable population of tissuegenic cells caused to be in contact with the growth-conductive matrix; methods to fabricate implants; methods of fabricating the implants; and use of the implants in tissue repair.

Claims

1. A tissue-derived implant for implantation in a recipient allogeneic to a donor of the implant, the implant as a whole comprising:

(a) at least one tissue-derived growth conductive matrix of the donor from which measurable immunologically reactive hematopoietic cells have been removed; and

(b) at least one viable population of nonexpanded tissuegenic cells endogenous to the growth conductive matrix of the donor that remains adherent to and resident in an endogenous milieu of the growth conductive matrix;

with the proviso that, before implantation, the implant is not reconstituted with cells exogenous to the tissue-derived growth conductive matrix of the donor.

2. The implant according to claim 1, wherein the implant further comprises at least one growth-inductive component.

3. The implant according to claim 2, wherein the growth-inductive component is tissue-derived.

4. The implant according to claim 3, wherein the tissue-derived growth-inductive component comprises demineralized cortical bone.

5. The implant according to claim 3, wherein the tissue-derived growth-inductive component is derived from extracellular matrix.

6. The implant according to claim 3, wherein the tissue-derived growth-inductive component comprises a growth medium derived from expanded tissuegenic cells.

7. The implant according to claim 3, wherein the tissuegenic cells adherent to and resident in the endogenous milieu of the growth conductive matrix secrete the at least one tissue-derived growth-inductive component.

8. The implant according to claim 3, wherein the at least one tissue-derived growth-inductive component comprises at least one cytokine.

9. The implant according to claim 3, wherein the at least one tissue-derived growth-inductive component comprises at least one growth factor.

10. The implant according to claim 9, wherein the least one growth factor is selected from the group consisting of fibroblast growth factor-2 (FGF-2), fibroblast growth factor-5 (FGF-5), insulin-like growth factor 1 (IGF-1), neural epidermal growth-factor-like 1 (Nel-like 1, NELL1), transforming growth factor beta (TGF-β

), a bone morphogenic protein, bone morphogenic protein-2 (BMP-2), bone morphogenic protein-7 (BMP-7), platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), and a combination thereof.