Method of preparing bone material having enhanced osteoinductivity
Methods for increasing osteoinductivity and/or surface area of bone material are provided. The methods include providing bone material and dehydrating the bone material with a solvent at its critical point. A useful solvent for critical point dehydrating is carbon dioxide. Critical point dehydration resulting in increased osteoinductivity and/or surface area can be applied to many types of bone material including bone particles, bone chips, bone fibers, bone matrices, both demineralized and non-demineralized. An implantable composition having an enhanced osteoinductivity and/or osteoconductivity is also provided. The implantable composition contains demineralized bone matrix dried at critical point of carbon dioxide. Critical point dried fibers of a demineralized bone matrix have a BET value from about 40 m 2 /gm to about 100 m 2 /gm, a value that is 100 times higher than corresponding vacuum dried or lyophilized DBM fibers.
1. A method for producing an implantable bone composition having enhanced osteoinductivity comprising the steps of:
(a) providing a bone material in the form of a demineralized bone matrix comprising a plurality of fully demineralized, entangled bone fibers and surface demineralized bone chips;
(b) dehydrating the bone material via critical point drying with a solvent at its critical point to remove moisture content from the demineralized bone matrix to approximately 8% or less to produce a dehydrated bone material having a surface area with a BET value from about 1 m 2 /gm to about 5 m 2 /gm;
(c) disposing the dehydrated bone material within a polymer mesh;
wherein the weight ratio of the fully demineralized bone fibers to the surface demineralized bone chips within the dehydrated bone material is about 1:0.2.
2. A method of claim 1 , the critical point solvent comprises carbon dioxide or freon.
3. A method of claim 2 , wherein the dehydrated bone material comprises a surface area increased from about 3 to about 4 times when compared to a surface area of untreated bone material.
4. A method of claim 2 , wherein the critical point drying comprises dehydration with carbon dioxide at about 31.5° C. and about 1200 psi.
5. A method of claim 1 , wherein the demineralized bone matrix further comprises an osteoinductive additive selected from the group consisting of bone marrow aspirant, blood, blood products, synthetic and naturally-derived bone morphogenic proteins, growth factors, or mixtures thereof.
6. A method of claim 1 , wherein the demineralized bone matrix further comprises an osteoconductive additive selected from the group consisting of calcium phosphates, collagen, collagen-derivatives, calcium sulfate, naturally-derived allogenic bone mineral, naturally-derived autogenic bone mineral or mixtures thereof.
7. A method of claim 1 , wherein the plurality of fully demineralized bone fibers are dehydrated bone fibers comprising a surface area increased from about 6 to about 7 times when compared to a surface area of bone fibers of untreated demineralized bone matrix.
8. A method of claim 1 , wherein the dehydrated fibers of demineralized bone matrix comprise a surface area increased by about 100 times when compared to demineralized bone matrix fibers dried by vacuum or lyophilized.
9. A method of claim 1 , wherein the plurality of fully demineralized bone fibers are dehydrated bone fibers comprising a surface area having a BET value from about 40 m 2 /gm to about 100 m 2 /gm.
10. A method of claim 1 , wherein the plurality of fully demineralized bone fibers have an aspect ratio of about 50:1 to about 750:1.
11. A method of claim 1 , wherein the residual moisture content of the demineralized bone matrix is approximately 3%.
12. A method of claim 1 , wherein the polymer mesh is porous.
13. A method of claim 1 , wherein the polymer mesh comprises poly(lactic acid-glycolic acid), poly(lactic acid) or poly(glycolic acid).