Bone paste composition

Abstract

Bone paste compositions are described, which promote bone healing and remodeling by stimulating bone marrow elements using a combination of hemopoietic agents, angiogenic agents and a bone molecular signaling material.

1 . A composition comprising:
 (a) at least one hemopoietic agent;   (b) at least one angiogenic agent;   (c) a bone molecular signaling material;   (d) a scaffolding material comprising cancellous bone; and   (e) a gel component.   
     
     
         2 . The composition of  claim 1  wherein said gel component is present at 10-80% by volume of the composition. 
     
     
         3 . The composition of  claim 1  wherein said gel component comprises a 0.5-25% (w/v) concentration of a material selected from the group consisting of: chitin, chitosan, alginate, hyaluronic acid, and any combination thereof, wherein the gel component is present at 10-80% by volume of the composition. 
     
     
         4 . The composition of  claim 1  wherein the bone molecular signaling material is selected from the group consisting of: demineralized bone matrix, non-decalcified bone matrix, and a combination thereof. 
     
     
         5 . The composition of  claim 3  wherein the bone molecular signaling material comprises demineralized bone matrix and non-decalcified bone matrix and optionally hyaluronic acid, wherein said demineralized bone matrix is present at 5-50% by volume, and said non-decalcified bone matrix is present at 5-50% by volume of the composition. 
     
     
         6 . The composition of  claim 5  wherein hyaluronic acid is present at 5-30% by volume of the composition. 
     
     
         7 . The composition of  claim 1  wherein the at least one hemopoietic agent is selected from the group consisting of: erythropoietins, erythropoietin growth factors, hemopoietic factors, and hematogenous-stimulating factors. 
     
     
         8 . The composition of  claim 1  wherein the at least one angiogenic agent is selected from the group consisting of: angiogenins, vascular endothelial growth factors, chitins, chitosans, chitin derivatives and complexes, chitosan derivatives and complexes; hyaluronic acids, hyaluronans, hyaluronan derivatives, hyaluronan complexes; alginates alginate derivatives, alginate complexes, and any combination thereof. 
     
     
         9 . The composition of  claim 1  wherein the scaffolding material comprises cancellous bone milled to about 0.1-1.5 mm in its longest diameter and present at 10-50% by volume of the composition. 
     
     
         10 . The composition of  claim 1  further comprising a carrier encapsulating the at least one of the hemopoietic agent, the angiogenic agent, the bone molecular signaling material, the scaffolding material comprising cancellous bone, and the gel component. 
     
     
         11 . The composition of  claim 10  wherein the encapsulating carrier comprises a carrier structure selected from the group consisting of vesicles and micelles, the carrier structure formed of a compound selected from the group consisting of: hyaluronic acid, hyaluronates, alginates, chitosans, hydrocarbons, surfactants or any combination thereof. 
     
     
         12 . The composition of  claim 1 , wherein said hemopoietic agent comprises erythropoietin; said angiogenic agent comprises chitosan or a chitosan derivatives; the demineralized bone matrix is present at 10% or more by volume of the composition; the cancellous bone is present at 10% or more by volume of the composition; and the gel component is a 1% (w/v) concentration of chitosan, alginate, or a combination thereof. 
     
     
         13 . The composition of  claim 1 , wherein:
 a. the hemopoietic agent is selected from the group consisting of erythropoietin, hemopoietic factors, and a combination thereof;   b. the angiogenic agent is selected from the group consisting of chitosan and derivatives thereof;   c. the bone molecular signaling material comprises demineralized bone matrix present at least 10%;   d. the cancellous bone is present at at least 10%; and   e. the gel component is a more than 3% (w/v) concentration of hyaluronic acid or hyaluronans, or a combination thereof.   
     
     
         14 . The composition of  claim 13 , wherein the angiogenic agent comprises chitosan or a derivative thereof wherein the bone molecular signaling material comprises demineralized bone matrix present at at least 10% by volume; the cancellous bone is present at at least 10% by volume; and the gel material comprises an at least 20% (w/v) concentration of a material selected from the group consisting of: hyaluronic acid, hyaluronans, a combination thereof, and a combination of hyaluronans and chitosan. 
     
     
         15 . The composition of  claim 13 , wherein the erythropoietic agent comprises erythropoietin and or one or more additional hematopoietic factors; the angiogenic agent comprises chitosan, or a derivative thereof the bone molecular signaling material comprises demineralized bone matrix present at 10% to 50% by volume; the cancellous bone is present at 10% to 50% by volume; and the gel material is a 3% or less (w/v) concentration of alginate, or a mixture of alginate with chitosan. 
     
     
         16 . The composition of  claim 13 , wherein the erythropoietic agent comprises erythropoietin and one or more additional hematopoietic factors; the angiogenic agent comprises angiogenin, a vascular endothelial growth factor, chitosan, or a derivative thereof; the bone molecular signaling material comprises demineralized bone matrix present at 10% to 50% by volume; the cancellous bone is present at 10% to 50% by volume; and the gel material is a 3% (w/v) concentration of hyaluronic acid or hyaluronans, or a mixture of hyaluronic acid with chitosan. 
     
     
         17 . A bone paste composition comprising:
 a. one or more hemopoietic agents selected from a group consisting of: erythropoietin, erythropoietin growth factors, and hemopoietic factors, present in an amount from 10 to 50,000 U or 3% or less by volume of the composition;   b. one or more angiogenic agents selected from the group consisting of chitosan components of medium to high molecular weight, and hyaluronic acid components;   c. a bone molecular signaling material comprising demineralized bone matrix and non-decalcified bone matrix optionally in combination with hyaluronic acid, wherein said demineralized bone matrix is present at 5-50% by volume of the composition, and said non-decalcified bone matrix is present at 5-50% by volume of the composition, wherein when present hyaluronic acid is present at 5 to 20% of the composition;   d. a scaffolding material comprising cancellous bone, wherein said cancellous bone is milled to 0.1-1.5 mm in its longest diameter and is present at 10-50% by volume of the composition;   e. a gel material comprising a 0.5-25% (w/v) concentration of a compound selected from the group consisting of chitosans, alginates, hyaluronic acids, and any combination thereof.   
     
     
         18 . The composition of  claim 17  wherein the one or more angiogenic agents comprise chitosan components of medium to high molecular weight selected from the group consisting of chitosans, chitosan derivatives, and chitosan complexes. 
     
     
         19 . The composition of  claim 17  wherein the one or more angiogenic agents comprise hyaluronic acid components comprising a mixture of sulfated and non-sulfated hyaluronic acid components. 
     
     
         20 . (canceled) 
     
     
         21 . A composition comprising:
 a. at least one hemopoietic agent encapsulated in a carrier comprising at least one material selected from the group consisting of:   chitosan, an alginate and a hyaluronan, the carrier configured to provide continuous and slow release of the hemopoietic agent;   b. at least one angiogenic agent;   c. a bone molecular signaling material comprising demineralized bone matrix present at 5-50% by volume of the composition, non-decalcified bone matrix present at 5-50% of the composition, and optionally hyaluronic acid;   d. a scaffolding material comprising cancellous bone, wherein said cancellous bone is milled to 0.1-1.5 mm in its longest diameter and is present at 10-50% of the components;   e. a gel component comprising a 0.5-25% (w/v) concentration of a material selected from the group consisting of chitosan, alginate, hyaluronic acid, a combination of alginate and chitosan, and a combination of hyaluronic acid and chitosan, said gel component present at 10-80% by volume of the composition.   
     
     
         22 - 40 . (canceled)