Impact of electric fields applied to nanotubular TiO2 surfaces on the osteogenic differentiation of mesenchymal stem cells for guided tissue engineering

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In the previous funding period of this project, we have demonstrated the induction of osteogenic differentiation of mesenchymal stem cells (MSC) through long-term application of direct current electric fields (EF) on nanotubular TiO2 surfaces. We described the mechanism of EF-induced osteogenesis to be mediated through EF-triggered calcium signaling, gap junction activity and ATP as part of the signaling cascade. The present proposal for renewal aims at developing a short-term alternating current (AC) EF system that can be used to improve the osseointegration of TiO2-implants in vivo.To develop an EF biosystem which accelerates the osteogenic differentiation of MSC by short-term AC EF application, we will 1) optimize an AC EF system for MSC differentiation in vitro, 2) develop a liposomal delivery system of the EF-dependent target molecules (Ca2+, ATP and gap junction agonist) releasing from nanotubes by short-term EF, 3) modify nanotube structure/characteristics for enhanced storage capacity and improved electrical conductivity of TiO2 nanotubes to allow the efficient target molecule delivery, and 4) apply short-term EF with target molecules to ex vivo peri-implant bone defect explants for verifying the target molecule distribution and the early response of explant tissue to EF. The results of these studies will help to understand the role of electric fields and implant surface structures in the osteogenesis and create a new way of generating highly biocompatible implant surfaces for orthopedic and dental tissue engineering.