Why is the clinical application of Mg not well accepted yet?

Wider research context / theoretical framework: Permanent metal implants are associated with a notable risk of implant failure, infection, insufficient fracture healing, and chronic inflammation triggered by the immune system in a long term view by precipitations from the metal in the body. The beneficial aspects of magnesium (Mg)-based implants include good mechanical properties and bioresorbability and promotion of osteoblastogenesis in vitro. Mg-based implants give hope to improve mechanical bone structure during osteosynthesis and support bone formation, however, the underlying molecular mechanisms at degrading Mg surface remain unclear, hence Mg based implants are not yet accepted in the clinics. Hypotheses/research questions /objectives: So far no in vitro model exists which truly mimics the in vivo situation. However, in vivo models are intrinsically complex making the elucidation of mechanisms costly and time-consuming. Here, we aim to develop an in vitro system that allows to determine and compare parameters to mimic the fundamental in vivo environment. This bidirectional in vitro and in vivo approach is coupled with detailed characterization of the degradation rate controlling corrosion products and the cell response at the implant tissue interface. Approach/methods: To mimic the in vivo situation, we will use live cell monitoring of bone, immune and fibroblast cells in a novel designed flow chamber at cell culture conditions combined with state- of-the-art cellular fluorescence sensors for Mg 2+ and pH measurements. Therefore, Mg discs will be subcutaneously and transcortically implanted into rats, which will be then sacrificed at comparable time points of in vitro studies. Biological and material aspects of ex vivo and in vitro samples will be further investigated and compared. Level of originality / innovation: Our proposed work aims to develop novel prognostic in vitro models for elucidating: i) stimulating effect on bone formation, (ii) its impact on the tissue implant interface and iii) Mg implant corrosion mechanisms. We will closely compare in vitro analysis of the implant environment with implant degradation mechanisms in animal models to optimize our in vitro live recording setup and offer accurate predictions for physiological effects on in vivo implants. Primary researchers involved: The research team will include profound experts in the field of Mg-based implant pre-clinical and clinical research (Prof. Weinberg, Medical University of Graz, Austria), in material corrosion (Dr. Schmutz, Empa, Switzerland), in ion channels and live-cell signaling (PD Schindl, Medical University of Graz, Austria) and in fluorescence based sensor tools (Prof. Malli, Medical University of Graz, Austria). All project partners will benefit from each other by consolidating a highly inter- and transdisciplinary consortium. Being specialized in different research fields, severa l techniques and measurements will be combined by this unique consortium.