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Enhanced Bone Formation in Segmental Defects with BMP2 in a Biologically Relevant Molecular Context
Technical Report,30 Sep 2015,29 Sep 2016
University of California, Davis Davis United States
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Segmental bone defects occur frequently from high impact trauma, such as gun shots. These do not heal on their own once a critical size segment of bone is missing. One strategy to induce healing is to use bone-inducing proteins BMPs, that are soaked into soft collagen sponges and placed into the area of missing bone. While this approach works, massive doses of the BMPs are required, sometimes 100,000 times the dose of BMPs that occur naturally. These high doses have side-effects that can be very severe. In thinking about why such high doses are required, we hypothesized that it is because the BMPs are not provided in a biological context that is used by the body. A BMP-binding protein COMP was recently identified that is a natural component of tissues that are involved in bone formation. There is good evidence that BMPs bound to COMP protein have greater bone-forming activity than unbound BMPs. Our goal in this proposal is to use this BMP-binding protein as a natural molecular context for the BMPs. We will test whether providing the BMPs bound to COMP will reduce the amount of BMP that is required for healing of critical size segmental bone defects. This will ultimately be done in a rat model Aim2. Before animal model experiments can be performed, in Aim 1 we will first establish a formulation for the BMPCOMP complexes that optimally induces bone-forming activity.
APPROVED FOR PUBLIC RELEASE