Bone repair product and methods of use thereof
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. A method of preparing a bone repair composition, comprising:
a) processing devitalized periosteum derived from long bone in the presence of a physiologic solution to produce periosteum pieces that are sticky, wherein the devitalized periosteum is processed so that it contains one or more biologically active angiogenic growth factor(s), and wherein the periosteum does not comprise immunogenic components;
b) processing cancellous bone to produce cancellous bone chips 4 mm or smaller in size, wherein the cancellous bone chips comprise viable osteogenic cells;
c) demineralizing bone particles to produce demineralized bone matrix (DBM) particles; and
d) combining the periosteum pieces, the cancellous bone chips, and the DBM particles, wherein the DBM particles in the bone repair composition do not exceed 45% by weight of the cancellous bone chips in the bone repair composition, and wherein the periosteum pieces adhere to themselves, the cancellous bone chips, and the DBM particles, thereby producing the bone repair composition that is malleable and packable, and that contains viable osteogenic cells and one or more biologically active angiogenic growth factor(s).
2. The method of claim 1 , wherein processing the devitalized periosteum to produce periosteum pieces that are sticky is achieved by mincing or cutting.
3. The method of claim 1 , wherein the physiologic solution is physiologic saline or phosphate buffered saline (PBS).
4. The method of claim 1 , wherein the cancellous bone is selected from among long bone, ilium, talus and calcaneus.
5. The method of claim 4 , wherein the long bone is femur, tibia, fibula or humerus.
6. The method of claim 1 , wherein the cancellous bone chips are from about 125 μm to 3 mm or from about 125 μm to 4 mm in size.
7. The method of claim 1 , wherein demineralizing bone particles comprises acid extraction.
8. The method of claim 1 , wherein the DBM particles are produced from cancellous bone or from cortical bone.
9. The method of claim 1 , wherein the one or more biologically active angiogenic growth factor(s) comprise one or more of vascular endothelial growth factor (VEGF), platelet derived growth factor (PDGF), basic fibroblast growth factor (bFGF) and insulin-like growth factor-I (IGF-I).
10. The method of claim 1 , wherein the osteogenic cells comprise cells selected from among mesenchymal stem cells, osteoprogenitor cells, osteoblasts and osteocytes.
11. The method of claim 1 , wherein the osteogenic cells comprise mesenchymal stem cells that are CD105+ and/or CD166+.
12. The method of claim 1 , wherein the osteogenic cells comprise osteoprogenitor cells that are tissue non-specific alkaline phosphatase positive (TNAP+).
13. The method of claim 1 , wherein cell viability in the composition is greater than or equal to 1%.