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Novel in Vitro Modification of Bone for an Allograft with Improved Toughness Osteoconductivity
Final rept. 30 Sep 2012 29 June 2015
HENRY FORD HEALTH SYSTEM DETROIT MI
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The purpose of the project is to investigate a potential application of ALT-711 4,5-Dimethyl-3-2-oxo-2-phenylethyl-thiazolium chloride in improving both mechanical and biological quality of femoral cortical bone for the purpose of providing better allograft materials via chemically breaking down AGEs Advanced Glycation Endproducts in the bone matrix. AGEs are naturally accumulated with age in connective tissues and believed to have adverse effects on the biological and mechanical functions. Thus allografts sourced from bones with a high level of AGEs are likely to have a higher risk of nonunion and premature failure in the hosts. The current scope, as a proof of concept study, is to measure the effectiveness of ALT-711 on both cellular and mechanical characteristics of bones with and without prior glycation treatment an artificial method to increase AGEs. Effects of ALT-711 on osteogenic expression of stem cells on the bone substrates, cell division, apoptosis and mineralization as well as the R-curve parameters including crack propagation, fracture toughness and critical crack length were measured. We found that the crosslink breaker ALT-711 can modify bone matrix, affect its fracture behavior and affect stem cell differentiation when used to treat allograft bone. However, these effects were not uniform enough that the proposed crosslink breaking method can be directly translated in to a protocol for enhancement of allograft performance. Further understanding of the complex interactions among donor age, sex and the AGE type would be necessary to develop more effective approaches to selectively remove the relevant AGEs from the tissue. Such understanding may also be key to understanding age related bone fragility and the sex disparity in fracture risk.
APPROVED FOR PUBLIC RELEASE