Encapsulated AGF cells
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.
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 10 6 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 10 6 or more platelets per ml, 1.5×10 4 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.
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.
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 10 6 or more platelets per ml, 1.5×10 4 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.