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"Methods to Limit BMP-2 Activity to Improve
Bone Healing"

by
Sangeeta Subramanian
Biomedical Engineering Program
B.S., 2009 The University of Florida


Thesis Advisor: Patrick O’Connor, Ph.D.
Department of Microbiology, Biochemistry and Molecular Genetics

Tuesday, December 8, 2015
10:00 A.M., MSB Room E609b


Abstract

Bone morphogenetic protein-2 (BMP-2) is an osteoinductive growth factor used for spinal fusions, open tibia fractures, and oral maxillofacial procedures. Complications associated with BMP-2 use have been reported. Methods to reduce complications associated with BMP-2 use while maintaining osteoinductive efficacy would benefit patients. The goals of this research were to investigate methods for better utilizing BMP-2 and to develop analysis tools that better estimate healing. Human chondrocyte cells genetically modified to express human BMP-2 (TG-B cells) were implanted into diabetic and normal rat femoral defects. Bone and cartilage formation in the defect were measured. Analysis of the data showed that the TG-B cells did not induce bone formation in the femur defects and therefore failed to promote healing. Using the rat femoral defect model, BMP-2 was applied to collagen sponges that were inserted into the defect. Defects were then wrapped with experimental membranes containing salicylic acid to limit bone formation to the defect space, with control membrane, or no membrane. Bone formation within the defect and outside the defect (ectopic) was measured. One of the experimental salicylic acid membranes decreased ectopic bone formation without significantly affecting bone formation in the defect, suggesting that salicylic acid membranes may be useful guided bone regeneration devices to limit BMP-2 induced ectopic bone formation, a known complication of BMP-2 use. Lastly, a novel method for analyzing microCT images was developed to estimate bone strength. The method was validated by comparing estimated values obtained from images of rat femurs from a fracture study to their corresponding empirically determined mechanical values. The method was then applied to images obtained from the salicylic acid membrane study. The analysis suggests that this novel image analysis procedure can be refined to accurately predict bone strength from computerized tomography imagery.


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