Bone Morphogenetic Protein-2 Binds As ... - ACS Publications

Dec 15, 2005 - Recombinant human bone morphogenetic protein-2 (rhBMP-2) promotes bone growth but must be retained at the delivery site for optimal ...
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Biomacromolecules 2006, 7, 131-138

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Bone Morphogenetic Protein-2 Binds As Multilayers To A Collagen Delivery Matrix: An Equilibrium Thermodynamic Analysis Randy Morin,† David Kaplan,‡ and Bernardo Perez-Ramirez*,† Formulation and Process Development, Wyeth BioPharma, One Burt Road, Andover, Massachusetts 01810, and Department of Biomedical Engineering & Chemical and Biological Engineering, Tufts University, 4 Colby Street, Medford, Massachusetts 02155 Received July 1, 2005; Revised Manuscript Received October 14, 2005

Recombinant human bone morphogenetic protein-2 (rhBMP-2) promotes bone growth but must be retained at the delivery site for optimal efficacy in vivo. rhBMP-2 release from a collagen-based matrix has shown favorable pharmacokinetics. The present study assessed binding affinity and binding saturation of rhBMP-2 to a collagen matrix as a function of solution and rhBMP-2 isoform variables. Results indicate that rhBMP-2 binds to the collagen matrix with affinities on the order of 103 to 104 M-1. Maximum binding, ν, was primarily a function of pH for heterogeneous rhBMP-2 and the extended (T266/T266) isoform. However, binding saturation of the