Volume maintaining osteoinductive/osteoconductive compositions

Abstract

An osteoinductive/osteoconductive composition prepared from a quantity, of demineralized fibrous bone elements possessing an average surface area to volume ratio of about 100:1 to about 20:1, a quantity of mostly shaped regular non-fibrous bone elements possessing an average surface area to volume ratio of about 10:1 or less and a sufficient quantity of biocompatible fluid carrier sufficient to provide the composition as a deformable mass is provided herein. Also provided is a method of using the composition to repair a bone defect site.

1 . An osteoinductive and osteoconductive composition comprising: (a) a quantity of demineralized fibrous bone elements possessing an average surface area to volume ratio of about 100:1 to about 20:1, (b) a quantity of shaped non-fibrous bone elements possessing an average surface area to volume ratio of about 10:1 or less, and (c) a biocompatible fluid carrier, wherein the composition withstands a compressive force greater than 7.9 N without substantial deformation.  
   
   
       2 . The osteoinductive and osteoconductive composition of  claim 1  of which about 50 to about 100 percent by weight of the fibrous bone element is made up of demineralized fibrous bone elements having a median length of from about 2 mm to about 400 mm, a median thickness of from about 0.05 mm to about 2 mm and a median length to median thickness ratio of at least 10:1 up to about 500:1.  
   
   
       3 . The osteoinductive and osteoconductive composition of  claim 1  in which a shape of the non-fibrous bone elements is selected from the group consisting of triangular prism, sphere, cube, cylinder and other regular shapes.  
   
   
       4 . The osteoinductive and osteoconductive composition of  claim 1  wherein the bone elements are obtained from cortical autogenic, cortical allogenic, cortical xenogenic cancellous autogenic, cancellous allogenic, cancellous xenogenic, cortical transgenic, cancellous transgenic, corticocancellous autogenic, corticocancellous allogenic, corticocancellous xenogenic or corticocancelldus transgenic bone.  
   
   
       5 . The osteoinductive and osteoconductive composition of  claim 1  of which about 20 to about 80 weight percent of the non-fibrous bone elements of the invention are non-fibrous bone elements having a median length to median width to median height ratio of at least about 1:0.3:1 and up to about 1:5:1, a imedian length of from about 1 mm to about 10 mm, a median width of from about 1 mm to about 10 mm and a median height of from about 1 mm to about 10 mm.  
   
   
       6 . The osteoinductive and osteoconductive composition of  claim 1  wherein about 0 to about 50 percent by weight of the bone elements are mineralized.  
   
   
       7 . The osteoinductive and osteoconductive composition of  claim 1  wherein about 0 to about 80 percent by weight of the bone elements are partially demineralized.  
   
   
       8 . The osteoinductive and osteoconductive composition of  claim 1  wherein about 0 to about 100 percent by weight of the bone elements are demineralized.  
   
   
       9 . The osteoinductive and osteoconductive composition of  claim 1  further comprising a thixotropic agent.  
   
   
       10 . The osteoinductive and osteoconductive composition of  claim 1  further comprising at least one medically/surgically useful substance.  
   
   
       11 . The osteoinductive and osteoconductive composition of  claim 1  wherein the fibrous bone elements are entangled.  
   
   
       12 . The osteoinductive and osteoconductive composition of  claim 11  wherein the non-fibrous bone elements are thoroughly mixed in the entangled fibrous bone elements.  
   
   
       13 . The osteoinductive and osteoconductive composition of  claim 1  containing from about 20 to about 70 weight percent demineralized fibrous bone elements, from about 20 to about 70 weight percent non-fibrous bone elements, and from about 10 to about 80 weight percent fluid carrier.  
   
   
       14 . The osteoinductive and osteoconductive composition of  claim 1  wherein the ratio of fibrous to non-fibrous elements is about 0.2:1 to about 1:0.2.  
   
   
       15 . The osteoinductive and osteoconductive composition of  claim 1  further comprising at least one additive selected from the group consisting of autograft bone marrow aspirate, autograft bone, preparations of selected autograft cells, autograft cells containing genes encoding bone promoting action and autograft cells expanded outside the body and returned.  
   
   
       16 . The osteoinductive and osteoconductive composition of  claim 1  wherein the composition withstands a compressive force of at least about 10.3 N without significant deformation.  
   
   
       17 . The osteoinductive and osteoconductive composition of  claim 1  wherein the amount of mineral remaining in the elements allows for radiographic imaging of the composition.  
   
   
       18 . The osteoinductive and osteoconductive composition of  claim 1  further comprising at least one radiopaque material selected from the group consisting of barium sulfate, iodine containing compounds, titanium and mineralized bone.  
   
   
       19 . method of using the osteoinductive and osteoconductive composition of  claim 1  wherein the composition is packed appropriately into an appropriate size bone defect site.  
   
   
       20 . The method of  claim 19  wherein the composition is packed into the defect site utilizing at least one means selected from the group consisting of spatula, forceps, syringe and dental equipment.  
   
   
       21 . The method of  claim 19  wherein the defect site is selected from the group consisting of ulna defects, metaphyseal defects, tibia plateau defects, acetabular defects, sinus defects, long bone cortical defects, cranial defects, ilium defects, wrist/hand defects, ankle/foot defects and oral/maxillofacial defects.  
   
   
       22 . The method of  claim 19  wherein the composition further comprises at least one additional additive selected from the group consisting of autograft bone marrow aspirate, autograft bone, autograft cell preparations, autograft cells containing genes encoded for bone stimulating activity and autograft cells expanded outside the body and returned.  
   
   
       23 . The osteoinductive and osteoconductive composition of  claim 1  containing about X weight units of component (a), about Y weight units of component (b) and about Z weight units of component (c) a given amount of the composition exhibiting a greater resistance to deformation than the identical amount of a second osteoinductive and osteoconductive composition containing X+Y weight units of component (a), no amount of component (b) and Z weight units of component (c).