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 sheet comprising a blood plasma-derived plastic, wherein the blood plasma-derived plastic comprises at least partially dried clotted blood plasma, wherein the at least partially dried clotted blood plasma comprises whole plasma, including a plasma clot and serum.
2. The sheet of claim 1 , wherein the blood plasma-derived plastic further comprises one or more of a plasticizer, stabilizer, drug or other therapeutic, filler, porogen, crosslinker, polymeric material, tracer, labeled compound, and metal ion.
3. The sheet of claim 2 , wherein the blood plasma-derived plastic further comprises a plasticizer, and the plasticizer is selected from the group consisting of water, glycerol, and mixtures thereof.
4. The sheet of claim 3 , wherein the plasticizer is glycerol.
5. The sheet of claim 2 , wherein the blood plasma-derived plastic further comprises a crosslinker, and the crosslinker is selected from the group consisting of carbodiimides, Factor XIII, dihomo bifunctional NHS esters, genipin, and mixtures thereof.
6. The sheet of claim 5 , wherein the crosslinker is genipin.
7. The sheet of claim 2 , wherein the blood plasma-derived plastic further comprises a drug, and 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.
8. The sheet of claim 2 , wherein the blood plasma-derived plastic further comprises a porogen, and the porogen is soluble in an aqueous phase.
9. The sheet of claim 1 , wherein the blood plasma-derived plastic further comprises a biological response modifier, and the biological response modifier is a bioactive protein selected from the group consisting of hormones, growth factors, cytokines, extracellular matrix molecules, and mixtures thereof.
10. The sheet of claim 9 , wherein the biological response modifier is a bioactive protein and 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.
11. The sheet of claim 9 , wherein the biological response modifier is a bioactive protein and 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.
12. The sheet of claim 1 , wherein the sheet is pliant, elastic, or a combination thereof.
13. The sheet of claim 1 , wherein the sheet is rigid.
14. The sheet of claim 1 , wherein the sheet is up to 1000 μm in thickness.
15. The sheet of claim 1 , wherein the sheet comprises less than about 5 percent by weight water.
16. The sheet of claim 1 , wherein the sheet is stacked, laminated, layered, rolled, or any combination thereof.
17. The sheet of claim 1 , wherein the sheet comprises a gradient of physical or chemical characteristics.
18. The sheet of claim 17 , wherein the sheet comprises a gradient of physical characteristics, and the physical characteristics are selected from the group consisting of one or more of density, porosity, elasticity and tensile strength.
19. The sheet of claim 17 , wherein the sheet comprises a gradient of chemical characteristics, and the chemical characteristics comprise a variation in the concentration of one or more additional agents.
20. The sheet of claim 19 , wherein the one or more additional agents are selected from the group consisting of one or more of a plasticizer, stabilizer, growth factor, drug or other therapeutic, filler, porogen, crosslinker, biological response modifier, polymeric material, tracer, labeled compound, and metal ion.
21. The sheet of claim 17 , wherein the sheet has multiple gradients.
22. The sheet of claim 1 , wherein the sheet is formed into a tube, rod or filament.
23. The sheet of claim 1 , wherein the sheet further comprises a biocompatible mesh.
24. The sheet of claim 1 , wherein the sheet is biodegradable.
25. The sheet of claim 1 , wherein the blood plasma-derived plastic comprises one or more of roughened spots, pores, and holes.
26. The sheet of claim 1 , wherein the blood plasma-derived plastic retains biological activity.
27. The sheet of claim 1 , wherein the sheet comprises surface texturing.
28. The sheet of claim 1 , wherein the whole plasma is obtained from an autologous donor.
29. The sheet of claim 1 , wherein the whole plasma is obtained from allogeneic donors.
30. The sheet of claim 1 , wherein the at least partially dried clotted blood plasma is essentially fully dried.
31. The sheet of claim 1 , wherein the blood plasma-derived plastic further comprises at least one of the biological response modifier that is heat-sensitive.
32. The sheet of claim 1 , wherein the platelet concentration of the whole plasma in the blood plasma-derived plastic is increased compared to a baseline platelet concentration of whole plasma.
33. An elastic or elastomeric sheet comprising a blood plasma-derived plastic, wherein the blood plasma-derived plastic comprises at least partially dried clotted blood plasma, wherein the at least partially dried clotted blood plasma comprises whole plasma, including a plasma clot and serum.
34. A wound dressing comprising a sheet comprising a blood plasma-derived plastic, wherein the blood plasma-derived plastic comprises at least partially dried clotted blood plasma, wherein the at least partially dried clotted blood plasma comprises whole plasma, including a plasma clot and serum.
35. A surgical sheet comprising a sheet comprising a blood plasma-derived plastic, wherein the blood plasma-derived plastic comprises at least partially dried clotted blood plasma, wherein the at least partially dried clotted blood plasma comprises whole plasma, including a plasma clot and serum.