Controlled induction of bone regeneration with the pro-form of bone morphogenetic protein-2 (proBMP-2) and novel scaffolds and release systems

• Applicant: Professor Dr. Bernhard Frerich
• Subject Area: Dentistry, Oral Surgery
• Term: from 2007 to 2012
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 37843374

The cure of bone defects should be perfectly possible through regeneration aided by persistent inducers of osseous differentiation like bone morphogenetic protein- 2 (BMP-2). In previous studies the action of administered BMP-2 has been too short and considerable side effects were observed with higher dosages. The specific aim of the present proposal is the dose adjustment in order to circumvent the reported side effects by two approaches: i) the evaluation of a variant of BMP-2 (proBMP-2) that is supposed to have a protracted effect and allows prolonged action as compared to BMP-2, and ii) the development of novel nanocomposite based scaffolds combined with polymeric and lipid based drug delivery systems allowing continuous release of proBMP-2 / BMP-2 or other release profiles at nearly physiological levels. The in vivo models comprise ectopic bone induction in mice, orthotopic induction in a rat critical size cranial defect and the preclinical test in an ovine skull defect. The release will be monitored by ESR spectroscopy in vivo, microdialysis and biochemical methods. Cellullar invasion and bone formation will be assessed by cone beam computed radiography, bench top MRI, histomorphometry and RT-PCR of osteogenic markers.

• DFG Programme: Research Grants