Whole blood-derived coagulum device for treating bone defects

1. A whole blood-derived coagulum device (WBCD) for treating a bone defect in an individual comprising:

(a) whole blood,

(b) an osteogenic protein,

(c) exogenously provided calcium chloride, and

(d) optionally, an exogenously provided fibrin-thrombin mixture,

wherein the exogenously provided calcium chloride is present in an amount that is effective to provide a homogeneous, cohesive, syringeable, injectable, and malleable coagulum gel that is capable of maintaining presence in a bone defect site for a period of time sufficient to promote growth of new bone to fill the defect or to rebridge bone ends of the defect.

2. The WBCD according to claim 1 , wherein the whole blood is autologous whole blood drawn from the individual or whole blood that has been crossmatched with the individual.

3. The WBCD according to claim 1 , wherein the osteogenic protein is an osteogenic BMP.

4. The WBCD according to claim 3 , wherein the osteogenic BMP is selected from the group consisting of BMP-2, BMP-4, BMP-6, BMP-7, heterodimers thereof, and combinations thereof.

5. The WBCD according to claim 1 , wherein the exogenously provided calcium chloride provides calcium ions at a concentration in the range of 1 mM to 2.5 mM, inclusive.

6. The WBCD according to any one of claims 1 - 4 , wherein the exogenously provided calcium chloride is present in the range of 5 mM to 15 mM, inclusive.

7. The WBCD according to claim 1 , wherein the exogenously provided fibrin-thrombin mixture is present.

8. The WBCD according to claim 7 , wherein the exogenously provided fibrin-thrombin mixture provides fibrin in the range of 5 mg/mL to 10 mg/mL, inclusive.

9. The WBCD according to claim 7 , wherein the exogenously provided fibrin-thrombin mixture provides thrombin in the range of 0.5 mg/mL to 5 mg/mL, inclusive.

10. The WBCD according to claim 7 , wherein the exogenously provided fibrin-thrombin mixture is combined with the exogenously provided calcium chloride and the osteogenic protein to form a first mixture; followed by incubating the first mixture for at least 15 minutes; and thereafter the whole blood is added to the first mixture to form a second mixture, and the second mixture is incubated for about 20 minutes.

11. A method of treating a bone defect in an individual in need of treatment thereof comprising:

1. preparing an osteogenic whole blood-derived coagulum device (WBCD) by the steps comprising:

(a) combining:

(i) whole blood,

(ii) an osteogenic protein,

(iii) exogenously provided calcium chloride, and

(iv) optionally, a fibrin-thrombin mixture,

(b) incubating the ingredients combined in step (a) until a mechanically stable coagulum is formed,

wherein the exogenously provided calcium chloride is present at a concentration that is effective to provide a homogeneous, cohesive, syringeable, injectable, and malleable coagulum gel, and

2. administering the WBCD of step 1 to the bone defect in the individual.

12. The method according to claim 11 , wherein the whole blood is autologous whole blood drawn from the individual or whole blood that has been crossmatched with the individual.

13. The method according to claim 11 , wherein the osteogenic protein is an osteogenic BMP.

14. The method according to claim 13 , wherein the osteogenic BMP is selected from the group consisting of BMP-2, BMP-4, BMP-6, BMP-7, heterodimers thereof, and combinations thereof.

15. The method according to claim 11 , wherein the exogenously provided calcium chloride provides calcium ions at a concentration in the range of 1 mM to 2.5 mM, inclusive.

16. The method according to any one of claims 11 - 14 , wherein the exogenously provided calcium chloride is present in the range of 5 mM to 15 mM, inclusive.

17. The method according to claim 11 , wherein the exogenously provided fibrin-thrombin mixture is present.

18. The method according to claim 17 , wherein the exogenously provided fibrin-thrombin mixture provides fibrin in the range of 5 mg/mL to 10 mg/mL, inclusive.

19. The method according to claim 17 , wherein the exogenously provided fibrin-thrombin mixture provides thrombin in the range of 0.5 mg/mL to 5 mg/mL, inclusive.

20. The method according to claim 17 , wherein step (a) is carried out by preparing a first mixture by combining the exogenously provided fibrin-thrombin mixture, the exogenously provided calcium ion, and the osteogenic protein; followed by incubating the first mixture for at least 15 minutes; and thereafter adding the whole blood to the first mixture to form a second mixture, and incubating the second mixture for about 20 minutes.

21. The method according to claim 11 , wherein the WBCD is administered by implantation into the bone defect.

22. The method according to claim 11 , wherein the WBCD is administered by injection into the bone defect.

23. The method according to claim 11 , wherein the bone defect is a fracture.

24. The method according to claim 11 , wherein the individual has a metabolic bone disease.

25. The method according to claim 24 , wherein the metabolic bone disease is selected from the group consisting of osteoporosis, osteopenia, and Paget's Disease.

26. A kit for preparing a whole blood-derived coagulum device (WBCD) for treating a bone defect comprising:

1. a vial containing a lyophilized osteogenic BMP,

2. a buffer for reconstituting the lyophilized BMP powder,

3. a syringe and a needle for reconstituting the lyophilized BMP in the buffer,

4. a vacutainer for collecting a patient's blood,

5. a sterile solution of 1 M CaCl 2 ,

6. a fibrin-thrombin mixture,

7. a plastic, siliconized container for mixing whole blood with the reconstituted BMP,

8. a spatula or a syringe for applying WBCD to bone ends during open surgery, and

9. instructions for using the foregoing materials in the preparation of a WBCD in accordance with claim 1 using autologous or crossmatched blood.