Kickstarting BMP-2 induced Bone Tissue Engineering

Summary Growth factor-based therapies have been shown to facilitate bone tissue engineering. Bone morphogenetic protein-2 (BMP-2) is a growth factor extensively used in the clinic for the purpose of stimulating bone growth. Although preclinical studies showed impressive results and low side effect rates, the high doses needed for effective bone formation in humans are associated with various serious side effects. To prolong its site specific pharmacological actions, biomaterials are used for local delivery. However, the optimal delivery rate and biomaterial conditions are still unknown. This thesis focusses on identifying and optimizing parameters that influence BMP-2 release and corresponding bone formation. Adjustments of the growth factor release rate often requires changes to the biomaterial characteristics, which may influence bone formation. To solve this complex puzzle, a biomaterial was developed capable of modifying BMP-2 release without changing the biomaterial characteristics as well as modifying the biomaterial characteristics without changing the BMP-2 release profiles. Hereby this thesis demonstrated that the local pharmacological actions of BMP-2 are highly dependent on three main parameters, i.e. BMP-2 pharmacokinetics, biomaterial chemistry and application site. Whereas BMP-2 release profiles influenced bone formation when applied under the skin, no effect was seen when applied in a bone defect. Based on this thesis, we have to conclude that “one size fits all” will not apply for the optimal release profile in BMP-2 based bone tissue engineering. Most likely, biomaterial characteristics and release profiles need to be tailored to meet the requirements of the clinical application