PF4-depleted platelet rich plasma preparations and methods for hard and soft tissue repair

1. A method of repairing and regenerating a hard or soft tissue in a mammal, the method comprising:

(a) preparing a platelet-rich plasma preparation comprising activated platelets, wherein the platelet-rich plasma preparation is further characterized as having the following properties:

(i) it contains a reduced level of platelet factor 4 (PF4) relative to untreated controls,

(ii) content and activity of growth factors in the platelet-rich plasma preparation are preserved, and

(iii) it is free of other blood cells; and

(b) administering to the mammal a therapeutic amount of the platelet-rich plasma preparation,

wherein the therapeutic amount of the platelet-rich plasma preparation is effective to repair and regenerate the hard and soft tissue in the mammal.

2. The method of claim 1 , wherein the platelet-rich plasma preparation is prepared from whole blood.

3. The method of claim 2 , wherein the whole blood is autologous whole blood drawn from the mammal.

4. The method of claim 1 , wherein the platelet-rich plasma preparation is administered to the mammal with at least one graft.

5. The method according to claim 4 , wherein the graft is selected from the group consisting of: a bone graft, a skin graft, a cartilage graft, a ligament graft, a tendon graft, a peripheral nerve graft, and a combination thereof.

6. The method according to claim 4 , further comprising administering at least one cell type selected from the group consisting of a tissue specific cell, a stem cell, an autologous cell, and an allogeneic cell prior to administering the platelet rich plasma preparation to the mammal.

7. The method according to claim 1 , preparing step (a) further comprising:

(1) activating platelets of the platelet-rich plasma preparation, thereby producing an activated platelet-rich plasma preparation;

(2) adding to the activated platelet-rich plasma preparation a solid or semi-solid phase matrix conjugated with heparin, such that the solid or semi-solid phase matrix conjugated with heparin binds to at least some Platelet Factor 4 (PF4) in the activated platelet-rich plasma preparation; and

(3) removing from the activated platelet-rich plasma preparation the solid or semi-solid phase matrix conjugated with heparin to which the Platelet factor 4 (PF4) is bound, thereby reducing the level of platelet factor 4 (PF4) relative to untreated controls.

8. The method of claim 7 , wherein the solid or semi-solid phase heparin-conjugating matrix contains heparin-conjugated agarose beads, heparin-conjugated silica beads, heparin-conjugated Sepharose beads, heparin-Sephadex beads, heparin-conjugated alginate beads, heparin-conjugated, acrylic beads, or a combination thereof.

9. The method of claim 8 , wherein the solid or semi-solid phase heparin-conjugating matrix is in the form of packed beads, column, a 3D mesh, hollow fibers, or a gel.

10. The method of claim 7 , wherein binding of the solid or semi-solid phase matrix conjugated with heparin to at least some Platelet Factor 4 (PF4) in the platelet-rich plasma preparation is carried out by at least one method selected from the group consisting of: mass loading, batch loading, sequential loading, continuous loading, and a combination thereof.

11. The method of claim 7 , wherein the platelet-rich plasma preparation is prepared from whole blood.

12. The method of claim 7 , wherein the solid phase matrix conjugated with heparin is heparin-conjugated agarose.

13. The method of claim 7 , wherein platelets of the platelet-rich plasma preparation are activated by adding a platelet-activation reagent to the platelet-rich plasma preparation.

14. The method of claim 13 , wherein the platelet-activation reagent is selected from the group consisting of thrombin, collagen, thromboxane A2, ADP, and a combination thereof.

15. The method of claim 7 , wherein platelets of the platelet-rich plasma preparation are activated spontaneously upon storage.

16. The method of claim 1 , wherein the other blood cells are red blood cells.

17. A method of reducing inflammation, anti-angiogenesis and anti-osteogenesis in a soft and hard tissue of a mammal, the method comprising:

administering to the mammal a therapeutic amount of a platelet-rich plasma preparation comprising activated platelets,

wherein the platelet-rich plasma preparation is further characterized as having the following properties:

(i) it contains a reduced level of Platelet Factor 4 (PF4) relative to untreated controls,

(ii) content and activity of growth factors in the platelet-rich plasma preparation are preserved, and

(iii) it is free of other blood cells; and

wherein the therapeutic amount of the platelet-rich plasma preparation is effective to reduce inflammation, anti-angiogenesis and anti-osteogenesis in the mammal.

18. The method of claim 17 , wherein the platelet-rich plasma preparation is prepared from whole blood.

19. The method of claim 17 , wherein the Platelet Factor 4 (PF4)-reduced platelet rich plasma preparation is administered to the mammal with at least one graft.

20. The method according to claim 19 , wherein the graft is selected from the group consisting of: a bone graft, a skin graft, a cartilage graft, a ligament graft, a tendon graft, a peripheral nerve graft, and a combination thereof.

21. The method according to claim 19 , further comprising administering at least one cell type selected from the group consisting of a tissue specific cell, a stem cell, an autologous cell, and an allogeneic cell prior to administering the platelet rich plasma preparation to the mammal.

22. The method of claim 18 , wherein the whole blood is autologous whole blood drawn from the mammal.

23. The method of claim 17 , wherein the platelet-rich plasma preparation is administered to a wound site of the mammal.

24. The method of claim 23 , wherein the platelet rich plasma preparation is administered together with a wound dressing.