Elution Characteristics of Bone Morphogenetic Proteins from Demineralized Bone Matrix

Little is known of the elution characteristics of bone morphogenetic proteins (BMPs), proteins involved with the bone-forming mechanism, out of demineralized bone matrix (DBM).DBM is a type of graft commonly used for in-vivo orthopedic surgical treatments to repair various bone abnormalities.Knowledge of the elution characteristics of BMPs out of DBM could improve the understanding of DBM function and help optimize graft design. Two sets of experiments were performed in this study; one examining the elution of BMP-7 out of bovine DBM for a period of three months, and the other examines the elution of BMPs-2, -4, and -7 out of human DBM for seven days.For the first set of experiments, the elution characteristics of BMPs out of bovine DBM were examined in-vitro using a variety of approaches as a probe to determine the association of BMPs with DBM over time.Once the DBM is placed into an aqueous environment, and as DBM hydration time increases, there is an unexpected increase in DBM BMP content as well; for example, more BMPs in the DBM can be accounted for a few days into DBM hydration versus zero hours of DBM hydration.Results support the idea that DBM hydration time impacts the complex association of BMPs with DBM, and that elution of BMPs from DBM in an aqueous environment occurs over a period of several weeks to months, which is longer than would be expected to be necessary to effect bone repair.The second set of experiments was the first to measure, and attempt to analyze the elution of human BMPs from a human DBM bone graft.The elution profiles of the human DBM were similar to the bovine DBM for the most part; however, some of the differences observed could be due to the additional carrier added to the human DBM which was not present in the bovine DBM.The elution profiles of BMPs -2, -4, and -7 were qualitatively similar to each other, differing mainly in magnitude which appeared to be related to the initial concentrations of these individual BMPs in DBM. This was the longest-term, most detailed study of the elution of BMPs from DBM that has ever been conducted which is relevant to an understanding of the osteoinductive process as well as basic bone biology.The results from this study may also be used to optimize the concentration of BMPs in a graft which can increase safety and cost benefits, and ultimately maximize DBM graft function.