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Site-directed immobilization of BMP-2 and Noggin inhibitory peptides onto collagen beads for bone regeneration

: Siverino, Claudia; Nickel, Joachim; Walles, Heike

Tissue Engineering. Part A 21 (2015), Supplement 1, S.118-119
ISSN: 1937-3341
ISSN: 1937-335X
Tissue Engineering International & Regenerative Medicine Society (TERMIS World Congress) <4, 2015, Boston/Mass.>
Konferenzbeitrag, Zeitschriftenaufsatz
Fraunhofer IGB ()

Bone regeneration requires concomitant processes of osteogenesis and neovascularization. The use of new materials, cells and growth factors has been therefore in focus of bone tissue engineering. In this study, we want to covalently couple Bone Morphogenetic Protein 2 (BMP-2) variants onto collagen beads in a site directed manner and test their osteogenic potential in vitro and in vivo. Because of the problems observed in all the approaches developed to incorporate growth factors into biomaterials, such as surface adsorption or encapsulation within polymeric matrices, we decided to immobilize the growth factor BMP-2 site-directly to collagen beads by the use of “click chemistry”. This method potentially overcomes the drawbacks connected with surface absorption and encapsulation, such as the need of large amounts of BMP-2 and poor release-dose control. Additionally, the high local concentration of BMP-2 might cause serious side effects, such as bone overgrowth, osteolysis or inflammation. For this purpose, we created two BMP-2 variants through site directed mutagenesis, comprising one unique non-natural amino acid substitution in each chain of the mature polypeptide, allowing a site-specific coupling by a specified coupling chemistry. Apart from the physical and chemical aspects connected to the immobilization, we focused our attention on improving the growth factor´s bioactivity by a caption of the BMP antagonist Noggin. BMPs perform their pro-osteogenic effect by binding to and oligomerizing of membrane receptors. But this can be hampered by a variety of intracellular but also extracellular antagonists, such as Noggin. Noggin binds to BMPs and interferes with their ability to induce receptor dimerization. Here we screened phage display library, using different immobilized Noggin variants as targets. After three rounds of panning, individual clones are isolated and sequenced. The identified peptide sequences will subsequently be synthesized and analyzed in terms on their Noggin-binding characteristics and their potential to inhibit BMP-2 mediated biological responses. Both tools, the covalently coupled BMP-2 and the peptides, which might act as Noggin "deflectors" might produce an innovative biomaterial with superior bone healing properties.