Bone repair product and methods of use thereof

Patent metadata

Field	Value
Publication number	US-10729809-B2
Application number	US-201514849509-A
Country	US
Kind code	B2
Filing date	Sep 9, 2015
Priority date	Sep 19, 2014
Publication date	Aug 4, 2020
Grant date	Aug 4, 2020

Abstract

Provided herein is a bone repair composition that is composed of periosteum containing an angiogenic growth factor(s), cancellous bone chips containing viable osteogenic cells, and, optionally, demineralized bone matrix (DBM) chips. Also provided herein are articles of manufacture and methods of use thereof to treat bone defects.

First claim

What is claimed:

1. A bone repair composition, comprising:
a) cancellous bone chips, wherein the cancellous bone chips are 4 mm or smaller in size, and wherein the cancellous bone chips comprise viable osteogenic cells;
b) processed devitalized periosteum, wherein the periosteum is from long bone, wherein the periosteum has been minced into pieces in the presence of a physiologic solution, and wherein the periosteum does not comprise immunogenic components and comprises one or more biologically active angiogenic growth factor(s); and
c) demineralized bone matrix (DBM) particles, wherein the DBM particles do not exceed 45% by weight of the cancellous bone chips;
wherein the periosteum pieces are sticky and allow the bone chips and the DBM particles to adhere to each other to thereby form the bone repair composition that is malleable and packable, and that contains viable osteogenic cells and one or more biologically active angiogenic growth factor(s).

2. The composition of claim 1 , wherein the cancellous bone chips are selected from among long bone, ilium, talus and calcaneus bone chips.

3. The composition of claim 1 , wherein the cancellous bone chips are from about 125 μm to 4 mm or from about 125 μm to 3 mm in size.

4. The composition of claim 1 , wherein the cancellous bone chips are from about 600 μm to 2 mm in size.

5. The composition of claim 1 , wherein the long bone is femur, tibia, fibula or humerus.

6. The bone repair composition of claim 1 , wherein the physiologic solution comprises a salt composition and osmotic pressure of blood plasma.

7. The bone repair composition of claim 1 , wherein the physiologic solution comprises phosphate buffered saline or physiologic saline.

8. The composition of claim 1 , wherein the DBM is demineralized cortical bone or demineralized cancellous bone.

9. The composition of claim 1 , wherein the DBM particles are 4 mm in size or smaller.

10. The composition of claim 1 , wherein the DBM particles are from about 100 um to 600 um in size.

11. The composition of claim 1 , wherein the osteogenic cells comprise cells selected from among mesenchymal stem cells, osteoprogenitor cells, osteoblasts and osteocytes.

12. The composition of claim 1 , wherein the osteogenic cells comprise mesenchymal stem cells that are CD105+ and/or CD166+.

13. The composition of claim 1 , wherein the osteogenic cells comprise osteoprogenitor cells that are tissue non-specific alkaline phosphatase positive.

14. The composition of claim 1 , wherein cell viability in the composition is greater than or equal to 1%.

15. The composition of claim 1 , wherein the angiogenic growth factor(s) comprise one or more of vascular endothelial growth factor (VEGF), platelet derived growth factor (PDGF), basic fibroblast growth factor (bFGF) and insulin-like growth factor-I (IGF-I).

16. The composition of claim 1 that is essentially free of blood cells.

17. The composition of claim 1 that is cryopreserved.

18. A package or container, comprising the composition of claim 1 .

19. A bone repair composition that is prepared by a method comprising:
a) processing periosteum to produce devitalized periosteum pieces, wherein the periosteum is from long bone, wherein the periosteum is minced into pieces in the presence of a physiologic solution, and wherein the periosteum retains one or more biologically active angiogenic growth factor(s);
b) processing cancellous bone to produce cancellous bone chips, wherein the cancellous bone chips are 4 mm or smaller in size, and wherein the cancellous bone chips comprise viable osteogenic cells;
c) providing demineralized bone matrix (DBM) particles, wherein the DBM particles do not exceed 45% by weight of the cancellous bone chips; and
d) combining the periosteum pieces, the cancellous bone chips, and the DBM particles,
wherein the periosteum pieces are sticky and allow the bone chips and the DBM particles to adhere to each other to thereby form the bone repair composition that is malleable and packable, and that is not immunogenic and contains viable osteogenic cells and one or more biologically active angiogenic growth factor(s).

20. The bone repair composition of claim 19 , wherein the physiologic solution comprises a salt composition and osmotic pressure of blood plasma.

21. The bone repair composition of claim 19 , wherein the physiologic solution comprises phosphate buffered saline or physiologic saline.

22. The bone repair composition of claim 19 that is cryopreserved.

23. A method of repairing a bone defect, comprising administering to the site of the defect a composition of claim 1 .

24. The method of claim 23 , wherein the repair is associated with a procedure selected from among hip replacement operations, knee replacement operations, foot and ankle surgeries, spinal fusion procedures, repair of periodontal defects, treatment of osteoporotic fractures, repair of bone tumor defects, repair of cranial maxilla facial defects, and repair of bone fractures.

25. The method of claim 23 , wherein the bone defect is selected from among a simple fracture, compound fracture, non-union fracture, osteosarcoma fracture, avascular osteonecrosis, spinal fusion, and bone regeneration in orthopedic implants.

Assignees

• Osiris Therapeutics Inc

Inventors

• Uveges Thomas E
• Kuang Jin-Qiang
• Danilkovitch Alla
• Sinclair S Michael
• Geraghty Sandra D

Classifications

• A61L27/40

  Composite materials, i.e. containing one material dispersed in a matrix of the same or different material · CPC title

• A61L27/3683

  subjected to a specific treatment prior to implantation, e.g. decellularising, demineralising, grinding, cellular disruption/non-collagenous protein removal, anti-calcification, crosslinking, supercritical fluid extraction, enzyme treatment · CPC title

• A61P19/08

  for bone diseases, e.g. rachitism, Paget's disease · CPC title

• A61L27/365

  Bones · CPC title

• A61K38/1866

  Vascular endothelial growth factor [VEGF] · CPC title