Bone pastes comprising biofunctionalized calcium phosphate cements with enhanced cell functions for bone repair

Patent metadata

Field	Value
Publication number	US-2016354518-A1
Application number	US-201615241950-A
Country	US
Kind code	A1
Filing date	Aug 19, 2016
Priority date	Oct 21, 2011
Publication date	Dec 8, 2016
Grant date	—

Abstract

The invention provides injectable, biofunctional agent-containing calcium phosphate cement bone pastes for bone tissue engineering, and methods of making and using the same.

First claim

What is claimed is:

1 . A bone paste comprising calcium phosphate cement and one or more biofunctional agents, wherein the biofunctional agents are selected from the group consisting of RGD-containing peptides, fibronectin, fibronectin-like engineered polymer protein (FEPP), derived extracellular matrix (dECM), and platelet concentrate.

2 . The bone paste of claim 1 , wherein the bone paste comprises calcium phosphate cement and an RGD-containing peptide, wherein RGD-containing peptide is selected from the group consisting of RGD, G4RGDSP, RGDS, GRGD, GRGDGY, RGDSGGC, and GRGDS, and wherein RGD-containing peptide is present within a range of about 0.0005% to about 5% by mass.

3 . The bone paste of claim 1 , wherein the bone paste comprises calcium phosphate cement and fibronectin, wherein fibronectin is present within a range of about 0.0005% to about 5% by mass.

4 . The bone paste of claim 1 , wherein the bone paste comprises calcium phosphate cement and FEPP, wherein FEPP is present within a range of about 0.0005% to about 5% by mass.

5 . The bone paste of claim 1 , wherein the bone paste comprises calcium phosphate cement and dECM, wherein dECM is present within a range of about 0.001% to about 10% by mass.

6 . The bone paste of claim 1 , wherein the bone paste comprises calcium phosphate cement and platelet concentrate, wherein platelet concentrate is present within a range of about 0.001% to about 10% by mass.

7 . The bone paste of claim 1 , wherein the bone paste comprises calcium phosphate cement and any two of the biofunctional agents.

8 . The bone paste of claim 1 , wherein the bone paste comprises calcium phosphate cement and any three of the biofunctional agents.

9 . The bone paste of claim 1 , wherein the bone paste comprises calcium phosphate cement and any four of the biofunctional agents.

10 . The bone paste of claim 1 , wherein the bone paste comprises calcium phosphate cement and each of the five biofunctional agents.

11 . The bone paste of any one of claims 1 - 10 , wherein the calcium phosphate cement comprises one or more ingredients selected from the group consisting of tetracalcium phosphate (TTCP) (Ca 4 (PO 4 ) 2 O), dicalcium phosphate anhydrous (DCPA) (CaHPO 4 ), dicalcium phosphate dihydrate (CaHPO 4 .2H 2 O), tricalcium phosphate (Ca 3 [PO 4 ] 2 ), α-tricalcium phosphate (α-Ca 3 (PO 4 ) 2 ), β-tricalcium phosphate (β-Ca 3 (PO 4 ) 2 ), octacalcium phosphate (Ca 8 H 2 (PO 4 ) 6 .5H 2 O), amorphous calcium phosphate (Ca 3 (PO 4 ) 2 ), calcium carbonate (CaCO 3 ), calcium hydroxide (Ca[OH] 2 ), and hydroxyapatite (Ca 10 (PO 4 ) 6 (OH) 2 ), and mixtures thereof.

12 . The bone paste of any one of claims 1 - 10 , wherein the calcium phosphate cement comprises tetracalcium phosphate and dicalcium phosphate anhydrous.

13 . The bone paste of claim 12 , wherein the calcium phosphate cement comprises a molar ratio of tetracalcium phosphate to dicalcium phosphate anhydrous of about 1:5 to about 5:1.

14 . The bone paste of claim 12 , wherein the calcium phosphate cement comprises a molar ratio of tetracalcium phosphate to dicalcium phosphate anhydrous of about 1:3 to about 1:1.

15 . The bone paste of claim 12 , wherein the calcium phosphate cement comprises an approximately 1:1 molar ratio of tetracalcium phosphate to dicalcium phosphate anhydrous.

16 . The bone paste of any one of claims 1 - 10 , wherein the calcium phosphate cement further comprises chitosan.

17 . The bone paste of any one of claims 1 - 10 , wherein the calcium phosphate cement further comprises fibers.

18 . The bone paste of claim 17 , wherein the fibers are degradable.

19 . The bone paste of any one of claims 1 - 10 , wherein the calcium phosphate cement further comprises chitosan and degradable fibers.

20 . The bone paste of any one of claims 1 - 10 , wherein the calcium phosphate cement further comprises a porogen.

21 . The bone paste of claim 20 , wherein the porogen is NaHCO 3 and citric acid.

22 . The bone paste of claim 21 , wherein the mass fraction of NaHCO 3 is from about 5% to about 30%, and the mass fraction of citric acid is from about 50% to about 60%.

23 . The bone paste of claim 16 , wherein the bone paste comprises calcium phosphate cement and a RGD-containing peptide, wherein the RGD-containing peptide is present within a range of about 0.0005% to about 0.05% by mass, and wherein the RGD-containing peptide is covalently linked to said chitosan.

24 . The bone paste of any one of claims 1 - 10 , wherein the bone paste further comprises stem cells.

25 . The bone paste of claim 24 , wherein the cells are selected from the group consisting of human umbilical cord mesenchymal stem cells, bone marrow stem cells, embryonic stem cells, pluripotent stem cells, induced pluripotent stem cells, multipotent stem cells, progenitor cells, and osteoblasts.

26 . The bone paste of claim 24 , wherein the cells are attached to a surface of the bone paste, or the cells are interspersed throughout the bone paste, or both.

27 . The bone paste of any one of claims 1 - 10 , wherein the bone paste is injectable.

28 . A bone paste comprising calcium phosphate cement, one or more biofunctional agents and cell-encapsulating microbeads, wherein the biofunctional agents are selected from the group consisting of RGD peptide, fibronectin, fibronectin-like engineered polymer protein (FEPP), derived extracellular matrix (dECM), and platelet concentrate.

29 . The bone paste of claim 28 , wherein the bone paste comprises calcium phosphate cement and an RGD-containing peptide, wherein RGD-containing peptide is selected from the group consisting of RGD, G4RGDSP, RGDS, GRGD, GRGDGY, RGDSGGC, and GRGDS, and wherein RGD-containing peptide is present within a range of about 0.0005% to about 5% by mass.

30 . The bone paste of claim 28 , wherein the bone paste comprises calcium phosphate cement and fibronectin, wherein fibronectin is present within a range of about 0.0005% to about 5% by mass.

31 . The bone paste of claim 28 , wherein the bone paste comprises calcium phosphate cement and FEPP, wherein FEPP is present within a range of about 0.0005% to about 5% by mass.

32 . The bone paste of claim 28 , wherein the bone paste comprises calcium phosphate cement and dECM, wherein dECM is present within a range of about 0.001% to about 10% by mass.

33 . The bone paste of claim 28 , wherein the bone paste comprises calcium phosphate cement and platelet concentrate, wherein platelet concentrate is present within a range of about 0.001% to about 10% by mass.

34 . The bone paste of claim 28 , wherein the bone paste comprises calcium phosphate cement and any two of the biofunctional agents.

35 . The bone paste of claim 28 , wherein the bone paste comprises calcium phosphate cement and any three of the biofunctional agents.

36 . The bone paste of claim 28 , wherein the bone paste comprises calcium phosphate cement and any four of the biofunctional agents.

37 . The bone paste of claim 28 , wherein the bone paste comprises calcium phosphate cement and each of the five biofunctional agents.

38 . The bone paste of any one of claims 28 - 37 , wherein the ca

Assignees

• Xu Huakun
• Univ Maryland

Inventors

• Xu Huakun

Classifications

• A61L27/3834

  Cells able to produce different cell types, e.g. hematopoietic stem cells, mesenchymal stem cells, marrow stromal cells, embryonic stem cells · CPC title

• A61L27/20

  Polysaccharides · CPC title

• A61L2430/02

  for reconstruction of bones; weight-bearing implants · CPC title

• A61L27/227

  Other specific proteins or polypeptides not covered by A61L27/222, A61L27/225 or A61L27/24 · CPC title

• A61L24/0036

  Porous materials, e.g. foams or sponges · CPC title