Muhammad Hafizuddin bin Omar

• Large bone defects are a major clinical problem affecting elderly disproportionally, particularly indeveloped countries where this population is the fastest growing. Current treatments include autologous and allogenous bone grafts, bone elongation with the Ilizarov technique, bone graft substitutes, and electrical stimulation. Each of these approaches enjoys varying degrees of success, however, each also has its associated problems and complications. A new, still experimental, treatment is Tissue Engineering that combines scaffolds, osteogenic stem cells and growth factors, and is showing encouraging early results in preclinical and initial clinical studies. Electrical stimulation has been shown to enhance bone healing by promoting mesenchymal stem cell migration, proliferation, and differentiation. In the present study we combine Tissue Engineering with Electrical Stimulation and hypothesize that this combined approach will have a synergistic effect resulting in enhanced new bone formation. In our in vitro experiments we observed that the levels of electrical stimulation we tested had no cytotoxic effect, instead increased osteogenic differentiation, as determined by enhanced expression of the osteogenic marker, Alkaline Phosphatase. These findings support our hypothesis by demonstrating that in the tissue-engineering environment electrical stimulation promotes bone formation. The bioinformatics part of this project consisted of gene network analysis, identification of the top 10 osteogenic markers and analyzis of genegene interactions. We observed that in studies of stem cells from both human and rat the genes, BMPR1A, BMP5, TGFßR1, SMAD4, SMAD2, BMP4, BMP7, RUNX3, and CDKN1A, are associated with osteogenesis and interact with each other. We observed a total of 31 interactions for human and 29 interactions for rat stem cells. While this approach needs to be proven experimentally, we believed that these in vitro and in silico analyses could compliment each other and in doing so contribute to the field of bone healing research.