Methods and apparatus for manufacturing plasma based plastics and bioplastics produced therefrom
Blood-derived plastic articles prepared from compositions including blood and, in some embodiments, at least one crosslinking agent and/or at least one biological response modifier, that can be useful for biological applications such as wound repair and tissue grafts; methods of making and using the same; methods for assessing the concentration of a biological response modifier in an article; and systems for preparing blood-derived plastic articles are provided.
1. A blood-derived plastic article comprising at least partially dried clotted blood plasma, and at least one biological response modifier, wherein the at least partially dried clotted blood plasma comprises whole plasma, including a plasma clot and serum.
2. The blood-derived plastic article according to claim 1 , wherein the whole plasma is obtained from an autologous donor.
3. The blood-derived plastic article according to claim 1 , wherein the whole plasma is obtained from allogeneic donors.
4. The blood-derived plastic article according to claim 1 , wherein the at least partially dried clotted blood plasma is essentially fully dried.
5. The blood-derived plastic article according to claim 1 , wherein the average particle size of the at least partially dried clotted blood plasma is less than about 500 μm.
6. The blood-derived plastic article according to claim 5 , wherein the average particle size of the at least partially dried clotted blood plasma is less than about 150 μm.
7. The blood-derived plastic article according to claim 6 , wherein the average particle size of the at least partially dried clotted blood plasma is less than about 38 μm.
8. The blood-derived plastic article according to claim 1 , wherein the biological response modifier is a bioactive protein selected from the group consisting of hormones, growth factors, cytokines, extracellular matrix molecules and mixtures thereof.
9. The blood-derived plastic article according to claim 8 , wherein the bioactive protein comprises at least one growth factor selected from the group consisting of platelet derived growth factors (PDGF), acidic and basic fibroblast growth factors, transformation growth factor beta (TGF-beta), insulin like growth factors (IGF), epidermal growth factors (EGF), platelet-derived angiogenesis factors (PDAF), platelet-derived endothelial growth factors (PDEGF), tumor necrosis factor-alpha (TNF-α), tumor necrosis factor-beta (TNF-β), vascular endothelial growth factors (VEGF), epithelial cell growth factors (ECGF), granulocyte-colony stimulating factors (G-CSF), granulocyte-macrophage colony stimulating factors (GM-CSF), nerve growth factors (NGF), neurotrophins, erythropoietin (EPO), thrombopoietin (TPO), myostatin (GDF-8), growth differentiation factor-9 (GDF9), hepatocyte growth factors (HGF), platelet factors, and mixtures thereof.
10. The blood-derived plastic article according to claim 8 , wherein the bioactive protein comprises at least one extracellular matrix molecule selected from the group consisting of osteocalcin, osteonectin, fibrinogen, vitronectin, fibronectin, thrombospondin 1 (TSP-1), bone sialoprotein (BSP), proteoglycans and mixtures thereof.
11. The blood-derived plastic article according to claim 1 , wherein the at least one biological response modifier is present in the blood-derived plastic article in an amount of about 1 picogram per gram of the composition to about 20 milligrams per gram of the composition.
12. The blood-derived plastic article according to claim 1 , wherein the blood-derived plastic article further comprises at least one plasticizer.
13. The blood-derived plastic article according to claim 12 , wherein the at least one plasticizer is selected from water and glycerol.
14. The blood-derived plastic article according to claim 13 , wherein the at least one plasticizer is glycerol.
15. The blood-derived plastic article according to claim 12 , wherein the at least one plasticizer is present in an amount of about 0.1 to about 80 percent by weight of the blood-derived plastic article.
16. The blood-derived plastic article according to claim 1 , wherein the blood-derived plastic article further comprises at least one crosslinking agent.
17. The blood-derived plastic article according to claim 16 , wherein the at least one crosslinking agent is genipin.
18. The blood-derived plastic article according to claim 16 , wherein the at least one crosslinking agent is present in an amount of about 0.01 to about 20 percent by weight of the blood-derived plastic article.
19. The blood-derived plastic article according to claim 1 , wherein the blood-derived plastic article further comprises at least one drug.
20. The blood-derived plastic article according to claim 19 , wherein the drug is selected from the group consisting of: analgesics; anti-infective agents; antineoplastics; biologicals; blood modifiers; cardioprotective agents; cardiovascular agents; cholinesterase inhibitors; hormones; immunomodulators; immunosuppressives; ophthalmic preparations; respiratory agents; anti-inflammatory agents; skin and mucous membrane agents; anti-cancer agents; and mixtures thereof.
21. The blood-derived plastic article according to claim 1 , wherein the blood-derived plastic article further comprises at least one stabilizer.
22. The blood-derived plastic article according to claim 21 , wherein the stabilizer is selected from the group consisting of glycogen, sorbitol, mannitol, trehalose, maltitol, xylitol, isomaltitol, erythritol, amylose, amylopectin, inositol hexasulfate, sulfated beta-cyclodextran, betaine, and mixtures thereof.
23. The blood-derived plastic article according to claim 1 , wherein the blood-derived plastic article further comprises at least one filler.
24. The blood-derived plastic article according to claim 1 , wherein the blood-derived plastic article further comprises at least one particulate selected from the group consisting of hydroxyapatite, tricalcium phosphate, calcium phosphate, calcium sulfate and mixtures thereof.
25. The blood-derived plastic article according to claim 1 , wherein the blood-derived plastic article further comprises at least one porogen.
26. The blood-derived plastic article according to claim 25 , wherein the at least one porogen is soluble in an aqueous phase.
27. The blood-derived plastic article according to claim 26 , wherein the at least one porogen is sodium chloride.
28. The blood-derived plastic article according to claim 25 , wherein the at least one porogen is a sublimation porogen.
29. The blood-derived plastic article according to claim 28 , wherein the sublimation porogen is selected from the group consisting of ammonium acetate, ammonium chloride, ammonium sulfate, ammonium bicarbonate, ammonium carbonate, pyridinium trifluoroacetate and mixtures thereof.
30. The blood-derived plastic article according to claim 1 , wherein the blood-derived plastic article is at least partially coated with one or more of the at least one biological response modifier.
31. The blood-derived plastic article according to claim 1 , wherein the blood-derived plastic article is in the form of a film.
32. The blood-derived plastic article according to claim 1 , wherein the blood-derived plastic article is in the form of a powder or granules.
33. The blood-derived plastic article according to claim 1 , wherein the blood-derived plastic article comprises a laminated structure.
34. The blood-derived plastic article according to claim 33 , wherein the laminated structure is in the form of a stack of sheets, a tubular roll, or combination thereof.
35. The blood-derived plastic article according to claim 1 , wherein the blood-derived plastic article is in the form of a bone substitute, cartilage substitute, tendon substitute, ligament substitute, skin substitute, cornea substitute, stent, fixation plate, screw, suture, or staple.
36. The blood-derived plastic article of claim 1 , wherein the blood-derived plastic article is prepared by a process comprising heating the at least partially dried clotted blood plasma and the at least one biological response modifier to a temperature less than about 80° C.
37. The blood-derived plastic article of claim 1 , wherein the blood-derived plastic article is prepared by a process comprising molding the at least partially dried clotted blood plasma and the at least one biological response modifier at a temperature between about 25° C. and about 80° C.
38. The blood-derived plastic article of claim 1 , wherein the blood-derived plastic article is prepared by a process comprising plasticizing the at least partially dried clotted blood plasma and the at least one biological response modifier at a temperature between about 55 to about 65° C.
39. The blood-derived plastic article of claim 1 , wherein at least one of the at least one biological response modifier is heat-sensitive.
40. The blood-derived plastic article of claim 1 , wherein the at least one biological response modifier is heat-sensitive.
41. The blood-derived plastic article of claim 1 , wherein the blood-derived plastic article is elastic.
42. The blood-derived plastic article of claim 1 , wherein the blood-derived plastic article is rubbery.
43. The blood-derived plastic article of claim 1 , wherein the blood-derived plastic article is hard.
44. The blood-derived plastic article of claim 1 , wherein the platelet concentration of the whole plasma in the blood-derived plastic article is increased compared to a baseline platelet concentration of whole plasma.
45. A blood-derived plastic article comprising clotted blood plasma and at least one biological response modifier, wherein the clotted blood plasma comprises whole plasma, including a plasma clot and serum, and wherein the blood-derived plastic article is in the form of a film.
46. The blood-derived plastic article of claim 45 , wherein the platelet concentration of the whole plasma in the blood-derived plastic article is increased compared to a baseline platelet concentration of whole plasma.
47. A blood-derived plastic article comprising clotted blood plasma and at least one biological response modifier, wherein the clotted blood plasma comprises whole plasma, including a plasma clot and serum, and wherein the blood-derived plastic article is in the form of a powder or granules.
48. The blood-derived plastic article of claim 47 , wherein the platelet concentration of the whole plasma in the blood-derived plastic article is increased compared to a baseline platelet concentration of whole plasma.
49. A blood-derived plastic article comprising clotted blood plasma, and at least one biological response modifier, wherein the clotted blood plasma comprises whole plasma, including a plasma clot and serum, and wherein the blood-derived plastic article is in the form of a laminated structure.
50. The blood-derived plastic article according to claim 49 , wherein the laminated structure is in the form of a stack of sheets, a tubular roll, or combination thereof.
51. The blood-derived plastic article of claim 49 , wherein the platelet concentration of the whole plasma in the blood-derived plastic article is increased compared to a baseline platelet concentration of whole plasma.
52. A blood-derived plastic article comprising clotted blood plasma, and at least one biological response modifier, wherein the clotted blood plasma comprises whole plasma, including a plasma clot and serum, and wherein the blood-derived plastic article is in the form of a bone substitute, cartilage substitute, tendon substitute, ligament substitute, skin substitute, cornea substitute, stent, fixation plate, screw, suture, or staple.
53. The blood-derived plastic article of claim 52 , wherein the platelet concentration of the whole plasma in the blood-derived plastic article is increased compared to a baseline platelet concentration of whole plasma.