Developing a true prognostic in vitro model to elucidate magnesium implant corrosion and its stimulating effect on bone formation
Annelie-Martina Weinberg, Department of Orthopedics and Traumatology
Prof. Dr. Annelie-Martina Weinberg|
|Availability:||This position is available.|
Medical University of Graz
|Application deadline:||Applications are accepted between February 10, 2020 00:00 and March 30, 2020 23:59 (Europe/Zurich)|
Conventional permanent metal implants are associated with a notable risk of implant failure, infection, insufficient fracture healing, and chronic inflammation. The beneficial aspects of magnesium (Mg)-based implants include good initial mechanical properties followed by bioresorbability. High concentrations of Mg2+ released from Mg-based implants have been shown to promote osteoblastogenesis and to inhibit osteoclastogenesis in vitro. Accordingly, Mg-based implants give hope to improve mechanical bone structure during osteosynthesis and bone formation. However, as a first bottleneck in the definition of optimal implants, the underlying molecular interactions and processes at the degrading Mg-based implant surface remain unclear, making the Mg-based implant’s structural evolution unpredictable and not yet applicable in clinics. In vivo models, are, on the other side, complex black boxes with numerous known but also unknown interfering parameters making the elucidation of degradation mechanisms extremely costly and time-consuming. Accordingly, in vitro models exhibit a solution in which specific parameters can be controlled and, as a result, with which the in vivo degradation mechanisms and processes can be experimentally characterized and predicted. New predictive in vitro models are urgently needed enabling a quantum leap in this area.
Hypothesis and Objectives:
Our hypothesis is that we can develop in vitro models which are able to mimic the in vivo resorption situation as proven by the formation of similar corrosion product layers (characterized with advanced composition and structural methods). With these in vitro models, we will be able to compare and predict how different Mg alloys behave in vivo. Moreover, we will be able to elucidate the influence of cells on corrosion mechanism as well as the effects of corrosion products (dissolved ions, solids) on cell phenotype of bone and immune cells.
To test the hypothesis, real- and long-time monitoring of Mg2+ release and pH changes will be determined in vitro and accordingly, the cell fluid and single cell effects in contact with the Mg implant and Mg2+ release will be assessed. These real time recordings will allow to investigate the cell/implant interface and effects on cells (differentiation, proliferation) in an in vitro approach validated by in vivo experiments and explant surface characterization. To mimic the in vivo situation, we will use a novel designed flow chamber at cell culture conditions using a real physiological simulated body fluid (SBF, without non-physiological components like TRIS and HEPES, or high phosphate concentrations), and also combine it with state-of-the-art cellular fluorescence sensors for Mg2+ and pH measurements.
- Khadija G, Saleem A, Akhtar Z, Naqvi Z, Gull M, Masood M, et al. Short term exposure to titanium, aluminum and vanadium (Ti 6Al 4V) alloy powder drastically affects behavior and antioxidant metabolites in vital organs of male albino mice. Toxicology Reports. 2018;5:765–70.
- Zimmerli W, Sendi P. Pathogenesis of implant-associated infection: the role of the host. Semin Immunopathol. 2011 May 1;33(3):295–306.
- Staiger MP, Pietak AM, Huadmai J, Dias G. Magnesium and its alloys as orthopedic biomaterials: A review. Biomaterials. 2006 Mar 1;27(9):1728–34.
- Bonyadi Rad E, Mostofi S, Katschnig M, Schmutz P, Pawelkiewicz M, Willumeit-Römer R, et al. Differential apoptotic response of MC3T3-E1 pre-osteoblasts to biodegradable magnesium alloys in an in vitro direct culture model. J Mater Sci Mater Med [Internet]. 2017 [cited 2018 Jan 3];28(10).
- Grün, NG; Holweg, P; Tangl, S; Eichler, J; Berger, L; van den Beucken, JJJP; Löffler, JF; Klestil, T; Weinberg, AM. Comparison of a resorbable magnesium implant in small and large growing-animal models. Acta Biomater. 2018; 78(4): 378-386.
- Romani AMP. Cellular magnesium homeostasis. Archives of Biochemistry and Biophysics. 2011 Aug 1;512(1):1–23.
- Bischof H, Burgstaller S, Waldeck-Weiermair M, Rauter T, Schinagl M, Ramadani-Muja J, et al. Live-Cell Imaging of Physiologically Relevant Metal Ions Using Genetically Encoded FRET-Based Probes. Cells. 2019 May;8(5):492.
- Burgstaller S, Bischof H, Gensch T, Stryeck S, Gottschalk B, Ramadani-Muja J, et al. pH-Lemon, a Fluorescent Protein-Based pH Reporter for Acidic Compartments. ACS Sens. 2019 Apr 26;4(4):883–91.
- Malheiro V, Elbs-Glatz Y, Obarzanek-Fojt M, Maniura-Weber K, Bruinink A. Harvesting pre-polarized macrophages using thermo-responsive substrates. Scientific Reports. 2017 Feb 14;7:42495.
Graziani A, Poteser M, Heupel W-M, Schleifer H, Krenn M, Drenckhahn D, et al. Cell-Cell Contact Formation Governs Ca2+ Signaling by TRPC4 in the Vascular Endothelium EVIDENCE FOR A REGULATORY TRPC4-β-CATENIN INTERACTION. J Biol Chem. 2010 May 2;285(6):4213–23.