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Modeling Bone Morphogenetic Protein Binding Peptide Action on Perfused Osteoblast Growth

  • Author(s): Sun, Argus
  • Advisor(s): Murray, Samuel S
  • et al.
Abstract

Bone Morphogenetic Protein-2 (BMP-2) is a growth factor in the TGF-β cytokine family, among other ubiquitous effects in development, it promotes bone mineralization by inducing osteoblast differentiation from precursor cells. This effect is the basis of its use as a therapeutic in procedures such as spinal fusion. However, because of its ubiquitous nature, side effects such as inflammation and swelling of surrounding tissues can be seen when the amount of BMP-2 implanted and released is not regulated. In the extracellular space, BMP-2 has numerous endogenous binding proteins. Among these is secreted phosphoprotein 24 (spp24). This protein can be modified in hopes of isolating the residues necessary to bind with BMP-2. This binding protein and its peptide derivatives can be used to modulate the release of BMP-2. Using a collagen sponge as a

delivery vehicle, the rate and pattern of release can be analyzed. Collagen sponges can serve as tissue engineering scaffolds that can host cell growth. An analysis of growth factor release from implantable collagen sponges cannot ignore the effect of ingrowth of osteoblast precursor cells. To study BMP-2 release modulation by spp24 with cellular response as an output, a perfusion bioreactor can be used. Perfusion bioreactors immerse a scaffold in growth media, delivering nutrients and gases permitting cell growth. In the bioreactor efflux, the release of BMP-2 from the sponge can be quantified. A BMP-2 scaffold-bioreactor system has the advantage of being sufficiently well-characterized in terms of parameters to the point where simulation is possible. Furthermore, the designed bioreactor can be fabricated to verify the predictions made by simulation. Finally, the BMP-2 SMAD pathway can be used to create a cellular model to predict the response generated by BMP-2 release.

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