Products comprising an extracellular matrix material and osteogenic protein

Abstract

Osteogenic compositions include a decellularized extracellular matrix tissue and bone morphogenic protein, preferably BMP-2. The compositions make beneficial use of the BMP, which can be used at relatively low doses and can bind to native components (e.g., native sulfated glycosaminoglycans such as heparin and/or heparan sulfate) remaining in the decellularized extracellular matrix tissue. Methods for preparation and use of such compositions are also described. The compositions and related methods can be used in the treatment of diseased or damaged bone tissue.

1 . An osteogenic composition, comprising:
 a collagenous extracellular matrix tissue material; and   bone morphogenic protein.   
     
     
         2 . The composition of  claim 1 , wherein:
 the collagenous extracellular matrix tissue material is a solid; and   the bone morphogenic protein is impregnated in the solid.   
     
     
         3 . The composition of  claim 1 , wherein:
 the collagenous extracellular matrix tissue material retains native heparin from a source tissue for the collagenous extracellular matrix tissue material; and   at least a portion of the bone morphogenic protein is bound to the native heparin.   
     
     
         4 . The composition of  claim 1 , wherein:
 the bone morphogenic protein comprises recombinant human BMP-2.   
     
     
         5 . The composition of  claim 1 , wherein:
 the collagenous extracellular matrix tissue material retains native components, preferably native sulfated glycosaminoglycans, from a source tissue for the collagenous extracellular matrix tissue material; and   at least a portion of the bone morphogenic protein is bound to the native components.   
     
     
         6 . The composition of  claim 1 , wherein the bone morphogenic protein is present at a level in the range of about 75 μg to about 300 μg per gram (dry weight) of the collagenous extracellular matrix tissue material. 
     
     
         7 . The composition of  claim 1 , wherein the extracellular matrix tissue material retains native growth factors, glycosaminoglycans, proteoglycans and glycoproteins from a source tissue for the extracellular matrix tissue material. 
     
     
         8 . The composition of  claim 7 , wherein the collagenous extracellular matrix tissue material retains native FGF-2 from a source tissue for the extracellular matrix tissue material. 
     
     
         9 . The composition of  claim 8 , wherein the native FGF-2 is present in the collagenous extracellular matrix tissue material at a level of at least about 50 nanograms per gram of the collagenous extracellular matrix tissue material. 
     
     
         10 . The composition of  claim 1 , wherein the collagenous extracellular matrix tissue material comprises submucosal tissue. 
     
     
         11 . The composition of  claim 1 , wherein the collagenous extracellular matrix tissue material is a porcine collagenous extracellular matrix tissue material. 
     
     
         12 . The composition of  claim 1 , also comprising a calcium phosphate compound. 
     
     
         13 . The composition of  claim 12 , wherein the calcium phosphate compound includes hydroxyapatite, tricalcium phosphate, or a combination thereof. 
     
     
         14 . The composition of  claim 12 , wherein the calcium phosphate compound is in particulate form. 
     
     
         15 . The composition of  claim 14 , wherein the collagenous extracellular matrix has mineralized native collagen fibers, with the mineralized native collagen fibers including calcium phosphate particles adhered to, within, or captured between native collagen fibers of the extracellular matrix tissue material, and preferably wherein said native collagen fibers have diameters greater than the greatest cross-sectional dimension of the calcium phosphate particles. 
     
     
         16 . The composition of  claim 12 , wherein the bone morphogenic protein includes amounts bound to native heparin of the extracellular matrix tissue material and amounts bound to the calcium phosphate. 
     
     
         17 . The composition of  claim 12 , wherein the bone morphogenic protein includes amounts bound to native heparin, heparan sulfate and/or other native components of the extracellular matrix tissue material and amounts bound to the calcium phosphate. 
     
     
         18 . The composition of  claim 12 , wherein the bone morphogenic protein is present in an amount not exceeding 3 mg and/or wherein the bone morphogenic protein is constituted at least 95% by weight of recombinant human BMP-2. 
     
     
         19 - 22 . (canceled) 
     
     
         23 . The composition of  claim 1 , wherein the collagenous extracellular matrix tissue material comprises a collagenous extracellular matrix gel including a mixture of solubilized extracellular matrix components native to a source tissue for the collagenous extracellular matrix tissue material. 
     
     
         24 . The composition of  claim 1 , wherein the collagenous extracellular matrix tissue material comprises particles of the collagenous extracellular matrix tissue material. 
     
     
         25 . The composition of  claim 1 , which is a flowable composition. 
     
     
         26 . The composition of  claim 25 , wherein the flowable composition is settable after delivery to a patient so as to increase the viscosity of the flowable composition. 
     
     
         27 . The composition of  claim 26 , wherein the flowable composition is settable to a non-flowable solid after delivery to a patient. 
     
     
         28 . A method for treating a patient, comprising administering to the patient a composition according to  claim 1 , preferably wherein the patient is a human, and/or preferably wherein the bone morphogenic protein is administered at a total dose of 6 mg or less, more preferably 4 mg or less. 
     
     
         29 - 30 . (canceled) 
     
     
         31 . A method for preparing an osteogenic composition, comprising:
 combining bone morphogenic protein and a collagenous extracellular matrix tissue material.   
     
     
         32 . The method of  claim 31 , wherein the collagenous extracellular matrix tissue material includes native heparin from a source tissue for the collagenous extracellular matrix tissue material, and wherein said combining results in binding of the bone morphogenic protein to the native heparin. 
     
     
         33 . The method of  claim 31 , wherein the collagenous extracellular matrix tissue material includes native heparin, heparan sulfate and/or other native components from a source tissue for the collagenous extracellular matrix tissue material, and wherein said combining results in binding of the bone morphogenic protein to the native heparin, heparan sulfate and/or other native components. 
     
     
         34 - 48 . (canceled) 
     
     
         49 . The composition of  claim 1 , wherein the composition comprises the bone morphogenic protein at a level of about 25 micrograms to about 100 micrograms per cubic centimeter of the extracellular matrix tissue material and/or wherein the composition further comprises erythropoietin. 
     
     
         50 - 55 . (canceled)