Enhanced osteoinductive compositions, systems, and methods of manufacture
An enhanced osteoinductive composition is prepared by subjecting particulate bone to a demineralization process that is optimized based on the particle size. In broad particle size ranges, ground bone is separated by particle size and each size range is subjected to independent demineralization conditions that maintain high levels of endogenous growth factors found in bone. Following demineralization, the size ranges are recombined to create an enhanced osteoinductive composition. In narrow particle size ranges, bone is milled to achieve a predetermined size, and the demineralization process is adjusted to this size range. Size-optimized demineralization is also used to create enhanced demineralized bone matrix particles in the size range of <125 μm. Enhanced osteoinductive compositions using size-optimized demineralization bone matrix and protein isolation and/or bone gelatin creation techniques are disclosed. Tissue repair compositions using the enhanced osteoinductive particles are also disclosed.
1 . A method of forming soluble growth factor peptide solution, the method comprising:
milling or cryomilling cortical bone to a particle size range of <125 μm to form a cortical bone powder;
demineralizing the cortical bone powder through a first primary demineralization process comprising soaking the cortical bone powder for <30 minutes in a solution comprising 0.2 N to 1.0 N HCl to form a primary demineralized cortical bone mass;
conducting a second demineralizing on the primary demineralized cortical bone mass comprising soaking the primary demineralized cortical bone mass in 2 M to 4 M citric acid for a period of time to obtain a secondary demineralized bone mass and a demineralization supernatant; and
isolating a soluble growth factor peptide solution from the demineralization supernatant through a protein purification process.
2 . The method of claim 1 , wherein the protein purification process comprises a dialysis process or a diafiltration process with a molecular weight cut off of 10 kDa or less.
3 . The method of claim 1 , further comprising drying the soluble growth factor peptide solution to form a growth factor peptide powder.