(55b) Release Characteristics and Osteogenic Activity of rhBMP-2 Grafted to Resorbable Nanoparticles

Mercado, A. - Presenter, University of South Carolina

Recombinant human bone morphogenetic protein-2 (rhBMP-2) is a potent differentiation factor that accelerates bone formation but diffusion of the protein away from the intended site of regeneration can cause bone overgrowth. Functionalized biodegradable nanoparticles (NPs) provide reactive groups and large surface area for grafting rhBMP-2 to reduce protein diffusion and maintain sufficient concentration of rhBMP-2 for recruitment and differentiation of osteoprogenitor cells. The objective of this work was to investigate release characteristics and osteogenic activity of rhBMP-2, grafted to biodegradable NPs based on succinimide-terminated poly(lactide fumarate) (PLAF-NHS) and poly(lactide-co-glycolide fumarate) (PLGF-NHS) macromers. The macromers were self-assembled in the presence of amphiphilic poly(lactide-co-ethylene oxide fumarate) (PLEOF) macromer and rhBMP-2 was grafted by the reaction of amine groups of the protein with succinimide groups of the NPs. The release of rhBMP-2 from the NPs, measured by ELISA, was linear with time in the first two weeks, and 24.70±1.30% and 48.7±0.7% of the grafted protein was released in the enzymatically active conformation after complete degradation/erosion of PLGF-NHS and PLAF-NHS NPs, respectively. In vitro osteogenic activity of the released rhBMP-2 was determined by incubation with bone marrow stromal (BMS) cells. After 21 days of incubation, rhBMP-2 grafted to PLAF-NHS and PLGF-NHS NPs was as effective in inducing mineralization as the native rhBMP-2 directly added to the cell culture media.