Impaired healing of fractures and other skeletal wounds is often associated with disability and increased morbidity. The hypothesis is that abnormal bone repair results from an osteoconductively and osteoinductively deficient bone matrix conducive to diminished cellular differentiation and growth. It has recently been observed by our group that demineralized bone matrix (DBM), in addition to augmenting bone repair when implanted in cranial defects and in segmental defects it acceleration healing after percutaneous injection. It is now proposed to study skeletal repair by bone growth or differentiation factors with carriers appropriate for percutaneous delivery to the wound site. Bone repair will be stimulated in animal models by injecting purified bone morphogenetic protein (BMP), PDGF and TGFbeta absorbed on microcrystalline hydroxyapatite, or as suspensions in type I collagen, using for comparison a standardized preparation of DBM powder. Microcrystalline hydroxyapatite carrier, DBM powder, and purified BMP will be prepared by methods based on our earlier work. Recombinant PDGF and TGFbeta are commercially available. A retention chamber, made of demineralized cortical bone, will be utilized to test each preparation for osteogenic activity before and after BMP inactivation by trypsin or guanidine.HC1 extraction. Stimulation of repair will be evaluated radiographically, biomechanically, histologically and biochemically in a fibula segmental defect and a non-union model. The proposed work is expected to provide important information on the stimulation of skeletal repair and lead to useful clinical applications as in the treatment of fracture non-unions by percutaneous injection of bone inducing agents.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
7R01AR040064-02
Application #
3160355
Study Section
Orthopedics and Musculoskeletal Study Section (ORTH)
Project Start
1990-09-30
Project End
1995-05-31
Budget Start
1990-09-30
Budget End
1991-05-31
Support Year
2
Fiscal Year
1990
Total Cost
Indirect Cost
Name
University of Florida
Department
Type
Schools of Medicine
DUNS #
073130411
City
Gainesville
State
FL
Country
United States
Zip Code
32611
Chakkalakal, D A; Mashoof, A A; Novak, J et al. (1994) Mineralization and pH relationships in healing skeletal defects grafted with demineralized bone matrix. J Biomed Mater Res 28:1439-43