Bone repair product and methods of use thereof

Abstract

Provided herein is a bone repair composition that is composed of periosteum containing an angiogenic growth factor(s), cancellous bone chips containing viable osteogenic cells, and, optionally, demineralized bone matrix (DBM) chips. Also provided herein are articles of manufacture and methods of use thereof to treat bone defects.

1 - 23 . (canceled) 
     
     
         24 . A bone repair composition, comprising:
 (a) cancellous bone chips;   (b) demineralized bone matrix (DBM) chips; and   (c) bone marrow, whereby the bone repair composition mediates angiogenesis.   
     
     
         25 . The bone repair composition of  claim 24 , wherein the cancellous bone chips comprise viable osteogenic cells. 
     
     
         26 . The bone repair composition of  claim 24 , wherein the bone marrow comprises bone marrow aspirate. 
     
     
         27 . The composition of  claim 24 , wherein the cancellous bone chips are selected from one or more of the long bone, ileum, talus and calcaneus, wherein optionally the long bone is the femur, tibia, fibula, or humerus. 
     
     
         28 . The composition of  claim 24 , wherein the cancellous bone chips are from about 125 μm to 3 mm, or from about 125 μm to 4 mm in size, or are 4 mm or smaller, or are from about 125 μm to 3 mm, or from about 125 μm to 4 mm, or from about 600 μm to 2 mm in size, or are 4 mm or smaller. 
     
     
         29 . The composition of  claim 24 , wherein the DBM is demineralized cortical bone or demineralized cancellous bone, and wherein DBM chips are less than 4 mm in size, less than 600 μm in size, or from about 100 μm to 600 μm in size. 
     
     
         30 . The composition of  claim 24 , wherein the DBM is present at from about 1% to 45%, from about 25% to 45%, or at no more than 45% by weight (mass/mass) of the cancellous bone chips comprising osteogenic cells. 
     
     
         31 . The composition of  claim 24 , wherein the composition comprises an angiogenic growth factor selected from one or more of endothelial growth factor (VEGF), platelet derived growth factor (PDGF), basic fibroblast growth factor (bFGF) and insulin-like growth factor-I (IGF-I). 
     
     
         32 . The composition of  claim 31 , wherein the concentration of the angiogenic growth factor in the composition is each independently at least 40 pg/mL. 
     
     
         33 . The composition of  claim 24 , wherein the composition exhibits one or more further activity selected from osteoconductive, osteoinductive, or osteogenic activity. 
     
     
         34 . The composition of claim  2 , wherein the osteogenic cells comprise cells selected from one or more of CD105+ and/or CD166+ mesenchymal stem cells, tissue non-specific alkaline phosphatase positive (TNAP+) osteoprogenitor cells, osteoblasts, and osteocytes. 
     
     
         35 . The composition of claim  2 , wherein the cell viability in the composition is greater than or equal to 50%. 
     
     
         36 . The composition of claim  2 , wherein the composition comprises at least 1×10 4  cells/cc. 
     
     
         37 . The composition of  claim 36 , wherein the composition is substantially free of blood cells, CD31+ cells, and CD45+ cells. 
     
     
         38 . The composition of claim  1 , wherein the composition is cryopreserved. 
     
     
         39 . A package or container, comprising the composition of claim  1 , wherein the container is a straight sided jar or a tray. 
     
     
         40 . A method of repairing a bone defect, the method comprising apply the composition of claim  1  to a bone defect, wherein the bone defect results from a developmental failure, degeneration or trauma, wherein the repair is associated with a procedure selected from among induction of bone formation for hip replacement operations, knee replacement operations, foot and ankle surgeries, spinal fusion procedures, repair of periodontal defects, treatment of osteoporosis, repair of bone tumor defects, dental procedures, repair of cranial maxilla facial defects and repair of bone fractures or defects. 
     
     
         41 . The method of  claim 40 , wherein the defect is selected from among a simple fracture, compound fracture, external fixation, internal fixation, joint reconstruction, arthroplasty, degenerative disc disease, avascular osteonecrosis, osteosarcoma fracture, fracture non-unions, spinal fusion, disc augmentation, and bone regeneration in orthopedic implants. 
     
     
         42 . A method of preparing a bone repair composition, the method comprising combining bone marrow aspirate comprising one or more biologically active angiogenic growth factor(s) and isolated cancellous bone chips, wherein the cancellous bone chips are processed from cancellous bone by one or more of blending, milling, grating, and grinding to produce the bone chips, and wherein the cancellous bone chips are processed to comprise viable osteogenic cells. 
     
     
         43 . The method of  claim 42 , further comprising performing a cryopreservation process comprising storing the composition at a temperature of −20° C. to −196° C., wherein cell viability of osteogenic cells is retained post-thaw.