Novel in Vitro Modification of Bone for an Allograft with Improved Toughness Osteoconductivity

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 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. We will measure effects of ALT-711 on osteogenic expression of stem cells on the bone substrates and also measure fracture toughness, a key measure of strong bone. We have demonstrated thus far ALT-711 has weak but measurable positive effects on the osteogenic expression of stem cells on bones without ribose treatment. We also have demonstrated ALT-711 is able to reverse the fluorescence level assumed to be correlated to the amount of AGEs previously increased by glycation. As such, we are encouraged by the preliminary data and now focusing our efforts in completing rest of the tasks assigned to the project. We expect to complete the work in the next period.