Regeneration of large, segmental bone defects by implantation of gene-activated fat tissue

• Applicant: Dr. Oliver Betz
• Subject Area: Orthopaedics, Traumatology, Reconstructive Surgery
• Term: from 2011 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 191446929

Treatment of large bone defects remains a challenge for surgeons. Current ex vivo gene transfer strategies have been successful in preclinical bone repair studies. However, translation into a clinical setting is difficult due to the complexity and high cost of the approach. Thus, the aim of this study is to develop an expedited, cost-effective and efficient method for the repair of critical size bone defects. The bone repair technology presented in this proposal does not require the isolation and expansion of osteoprogenitor cells. Instead, fat tissue is harvested, directly activated by transfer of osteogenic genes, and implanted into the bone defect. In the first year of the proposed study, we will compare the bone regeneration capacities of fat tissue grafts activated by either Bone Morphogenetic Protein (BMP) -2, BMP-7 or BMP-9. Repair of segmental bone defects in rat femora will be analyzed at 6 and 12 weeks after surgery by histology, micro-computed tomography and biomechanical testing. In the second year, we will compare treatment with fat tissue activated by the most promising growth factor from the first year study to autologous bone grafting and evaluate the long term outcome. Additionally, in order to assess engraftment and to investigate the contribution of fat tissue to bone formation we will perform fluorescence in situ hybridization using Y-chromosome paint.

• DFG Programme: Research Grants