Encapsulated AGF cells

• US 20050008629A1
• Filed: 05/07/2003
• Published: 01/13/2005
• Est. Priority Date: 05/08/2002
• Status: Abandoned Application

• Current Assignee: Biomet Biologics LLC (Zimmer Biomet Holdings, Inc.)
• Original Assignee: Interpore Orthopaedics Inc. (Zimmer Biomet Holdings, Inc.)
• Inventors: Arm, Douglas M.
• Application Number:
  US10/434,442
• Publication Number:
  US 20050008629A1
• Time in Patent Office: Days
• US Class Current: 424/93.710
• CPC Class Codes: A01N 1/0231 Chemically defined matrices, e.g. alginate gels, for immobilising, holding or storing cells, tissue or organs for preservation purposes; Chemically altering or fixing cells, tissue or organs, e.g. by cross-linking, for preservation purposes
• CPC Class Codes: B82Y 30/00 Nanotechnology for materials or surface science, e.g. nanocomposites

Abstract

This invention provides a composition of encapsulated blood constituents. The invention provides methods to make and use the encapsulated blood constituents, e.g., to stimulate and support tissue regeneration with autologous growth factors.

Claims

1. Encapsulated blood constituents comprising:

a matrix comprising water permeable pores; and

,

one or more blood constituents encapsulated by the matrix;

wherein the blood constituents are separated or concentrated blood constituents.

2. The encapsulated blood constituents of claim 1, wherein the matrix forms a membrane structure.

3. The encapsulated blood constituents of claim 2, wherein the matrix comprises material selected from the group consisting of:

an alginate, a self assembled monolayer, cross-linked blood proteins, gelatin, polyvinyl alcohol, ethylcellulose, styrene maleic anhydride, self-assembled surface active layers, and cellulose acetatephthalate.

4. The encapsulated blood constituents of claim 1, wherein the matrix comprises a three dimensional open pore matrix.

5. The encapsulated blood constituents of claim 4, wherein the open pore matrix comprises material selected from the group consisting of:

an alginate, cross-linked blood proteins, gelatin, polyvinyl alcohol, ethylcellulose, styrene maleic anhydride, self-assembled surface active layers, and cellulose acetatephthalate.

6. The encapsulated blood constituents of claim 1, wherein the matrix comprises one or more materials that substantially fail to initiate aggregation of platelets or clot formation in plasma.

7. The encapsulated blood constituents of claim 1, wherein the matrix comprises one or more biodegradable materials.

8. The encapsulated blood constituents of claim 1, wherein the pores have a molecular weight cut off of not more than about 500 kDa.

9. The encapsulated blood constituents of claim 8, wherein the pores have a molecular weight cut off of not more than about 100 kDa.

10. The encapsulated blood constituents of claim 9, wherein the pores have a molecular weight cut off of not more than about 3 kDa.

11. The encapsulated blood constituents of claim 1, wherein the blood constituents comprise one or more blood plasma proteins.

12. The encapsulated blood constituents of claim 1, wherein the blood constituents comprise platelets.

13. The encapsulated blood constituents of claim 1, wherein the blood constituents comprise white blood cells.

14. The encapsulated blood constituents of claim 1, wherein the blood constituents comprise buffy-coat.

15. The encapsulated blood constituents of claim 14, wherein the buffy-coat comprises 10⁶ or more platelets per ml, 1.5×

or more WBCs per ml, or 5 mg/ml or more of fibrinogen.

16. The encapsulated blood constituents of claim 1, wherein the blood constituents comprise blood cells which release one or more growth factors or cytokines.

17. The encapsulated blood constituents of claim 16, wherein the growth factors are selected from the group consisting of:

EGF, IGF, PDGF, TGF, VEGF and FGF.

18. The encapsulated blood constituents of claim 16, wherein the cytokines are selected from the group consisting of an interleukin, an interferon, a CSF, a compliment fragment, and a coagulation cascade fragment.

19. The encapsulated blood constituents of claim 1, further comprising supplemental constituents selected from the group consisting of:

a bioactive agent, a nutrient, a stability enhancing agent, an anticoagulant, and a drug.

20. A method of regenerating tissue, the method comprising:

separating or concentrating one or more blood constituents;

encapsulating the blood constituents in a matrix; and

,

embedding the encapsulated blood constituents at a tissue regeneration site;

thereby promoting regeneration of tissue at the site.

21. The method of claim 20, wherein the separating or concentrating of the blood constituents comprises processing whole blood or blood components with an automated instrument.

22. The method of claim 20, wherein the blood constituents comprise one or more blood plasma proteins.

23. The method of claim 20, wherein the blood constituents comprise platelets.

24. The method of claim 20, wherein the blood constituents comprise white blood cells.

25. The method of claim 20, wherein the blood constituents comprise buffy-coat.

26. The method of claim 25, wherein the buffy-coat comprises 10⁶ or more platelets per ml, 1.5×

10⁴ or more WBCs per ml, or 5 mg/ml or more of fibrinogen.

27. The method of claim 20, wherein the blood constituents and the tissue at the site of regeneration are autologous.

28. The method of claim 20, wherein the encapsulated blood constituents further comprise supplemental constituents selected from the group consisting of:

a bioactive agent, a nutrient, a stability enhancing agent, an anticoagulant, and a drug.

29. The method of claim 20, wherein the matrix forms a membrane structure.

30. The method of claim 20, wherein the matrix comprises material selected from the group consisting of alginate, cross-linked blood proteins, gelatin, polyvinyl alcohol, ethylcellulose, styrene maleic anhydride, self-assembled surface active layers, and cellulose acetatephthalate.

31. The method of claim 20, wherein the blood constituents and the tissue at the site of tissue regeneration are autologous.

32. The method of claim 20, wherein encapsulating the blood constituents comprises forming a continuous layer of polymeric material about aqueous droplets of the blood constituents.

33. The method of claim 20, further comprising releasing growth factors or cytokines from the encapsulated blood constituents at the tissue regeneration site.

34. The method of claim 33, wherein the growth factors are selected from the group consisting of:

EGF, IGF, PDGF, TGF, VEGF, and FGF.

35. The method of claim 33, wherein the cytokines are selected from the group consisting of:

an interleukin, an interferon, a CSF, a compliment fragment, and a coagulation cascade fragment.

36. The method of claim 20, further comprising blending the encapsulated blood constituents with a bone growth matrix or a cartilage growth matrix before embedding the encapsulated blood constituents at the site of tissue regeneration.

37. The method of claim 36, wherein the growth matrix is selected from the group consisting of:

porous ceramic, coralline hydroxyapatite, collagen, mineralized collagen, hyaluronic acid and derivatives, calcium carbonate, tri-calcium phosphate, an open pore biocompatible foam, hydroxyapatite ceramic, magnesium sulfate, polyester, autogenous bone, allograft bone, and allograft cartilage.

38. A method of providing autologous blood constituents, cytokines, or growth factors to a patient, the method comprising:

separating or concentrating blood constituents from the patient;

encapsulating the blood constituents in a matrix; and

,

transfusing the encapsulated blood constituents into the patient,

thereby providing the patient with autologous constituents or factors.

39. The method of claim 38, wherein the growth factors are selected from the group consisting of:

EGF, IGF, PDGF, TGF, VEGF, and FGF.

41. The method of claim 38, wherein the patient is a mammal.

42. The method of claim 38, wherein the separating or concentrating of the blood constituents comprises processing whole blood or blood components with an automated instrument.

43. The method of claim 38, wherein the blood constituents comprise one or more blood plasma proteins.

44. The method of claim 38, wherein the blood constituents comprise platelets.

45. The method of claim 38, wherein the blood constituents comprise white blood cells.

46. The method of claim 38, wherein the blood constituents comprise buffy-coat.

47. The method of claim 46, wherein the buffy-coat comprises 10⁶ or more platelets per ml, 1.5×

10⁴ or more WBCs per ml, or 5 mg/ml or more of fibrinogen.

48. The method of claim 38, wherein the encapsulated blood constituents further comprise supplemental constituents selected from the group consisting of:

a bioactive agent, a nutrient, a stability enhancing agent, an anticoagulant, and a drug.

49. The method of claim 38, wherein the matrix comprises material selected from the group consisting of alginate, cross-linked blood proteins, gelatin, polyvinyl alcohol, ethylcellulose, styrene maleic anhydride, self-assembled surface active layers, and cellulose acetatephthalate.

50. The method of claim 49, wherein the blood proteins are from the patient.

51. The method of claim 38, wherein encapsulating the blood constituents comprises forming a continuous layer of polymeric material about aqueous droplets of the blood constituents.

52. The method of claim 38, further comprising storing the encapsulated blood constituents.

53. The method of claim 38, wherein transfusing comprises injecting the encapsulated blood constituents into a peripheral blood vessel or a body compartment of the patient.

54. The method of claim 38, further comprising dissociating the matrix after transfusing the encapsulated blood constituents into the patient.

40. The method of claim, wherein the cytokines are selected from the group consisting of an interleukin, an interferon, a CSF, a compliment fragment, and a coagulation cascade fragment.