Two (2) recombinant human Bone Morphogenetic Proteins (BMP's), rhBMP-2 and rhBMP-7, are currently used in clinical applications to promote spinal fusion and fracture healing (Mont, Ragland et al. 2004). Over 6.3 million fractures occur each year in the United States alone (Praemer, Furner et al. 1999). Approximately 15% of fractures have delayed or impaired healing. The clinical applications currently in use, however, require open surgery to insert the carrier/BMP combination at the site of healing. There would be considerable clinical benefit from the ability to delivery BMP's via a minimally invasive procedure to accelerate fracture healing or treat delayed or non-unions. In this proposal, we present a novel approach for the development of an injectable delivery system for BMP-2. 1 major requirement for an injectable carrier for BMP-2 is the maintenance of an appropriate concentration of the osteogenic factor at the site of repair for sufficient time to allow bone-forming progenitor cells to migrate to the site, proliferate, and differentiate. A wide range of carriers have been described and characterized for delivery of BMP-2, however, none of them have a strong intrinsic affinity for BMP-2 sufficient for proper healing via an injectable. In fact, most injectable BMP/carrier combinations that have been explored to date lost 50% or more of the BMP after a few days in vivo (Seeherman, Li et al. 2003). We have identified a series of BMP-2 binding peptides using phage display that have strong affinity for BMP-2. Representative high affinity BMP-2 binding peptides will be chemically crosslinked to type I collagen to generate an injectable carrier that binds and retains BMP-2. These binding peptides will then be investigated for their ability to sustain the release of BMP-2 from a collagen matrix, while maintaining the growth factors bioactivity and improving its ability to promote bone formation in vivo. The development of this type of delivery matrix, which uses peptides with differing affinities for BMP, may allow for a greater degree of control of the release of BMP from the matrix, faster healing times, and enable new clinical treatments with BMP. Most importantly, the development of an injectable BMP-2 formulation would allow for the treatment of fractures with a minimally invasive procedure. Growth factors called Bone Morphogenetic Proteins (BMP's) are currently used to promote fracture healing. Over 6.3 million fractures occur each year in the United States alone and approximately 15% of fractures have delayed or impaired healing. The clinical applications currently in use, however, require open surgery to insert the carrier/BMP combination at the site of healing. There would be considerable clinical benefit from the ability to deliver BMP's via a minimally invasive procedure. In this proposal, we present a novel approach for the development of an injectable delivery system for BMP-2 that improves the retention and effectiveness of this growth factor at the site of repair. ? ? ?
| Hamilton, Paul T; Jansen, Michelle S; Ganesan, Sathya et al. (2013) Improved bone morphogenetic protein-2 retention in an injectable collagen matrix using bifunctional peptides. PLoS One 8:e70715 |
