Speaker
Description
Introduction: Biomechanical features and osteogenic properties of magnesium implants make them suitable for orthopedic applications. [1] Commonly used in vivo methods to investigate tissue response, such as histology and gene expression of peri-implant tissue, are terminal procedures that give a limited temporal and spacial view on the organism response to the implant. [2] Thus, systemic biomarkers of bone turnover currently used to diagnose and monitor musculoskeletal diseases may be of great value in the context of magnesium degradable implants. Biomarkers profile characterization can be used to follow the successful integration of the implant and tissue healing as well as addressing more accurate implant designs and chemical composition. In this study, we analyze systemic inflammatory and bone healing markers pattern expression after magnesium implantation and aim to correlate it with results of histopathology and implant surface analysis.
Methods: Animal experiments experiments are approved by Instituto Superiore di Sanità on behalf of Italian Ministry of Health and Ethical Panel (Prot. n° 299/2020-PR) and local ethics committee. Female Wistar rats (n=28) 12-week old were used to press-fit WE43 pins (1.6mm diameter *8mm length) transcortically into the diaphyseal region of the femur of both legs. Before surgery, and 1, 3, 7, 14, 28, 45 and 90 days after surgery, blood samples were collected for the analysis of inflammatory (IFNγ,IL-10 IL-1ɑ, IL-4, IL-6, CXCL1, MCP-1, TNFɑ ,VEGF) and bone regeneration (Osteopontin, Osteoprotegerin, FGF-23, DKK1, TIMP-1)markers using LUMINEX Immunoassay. Furthermore, on days 3,7,14 and 90 some animals were euthanized, one leg was used for histological H&E staining and the other for pins retrieval and SEM surface analysis
Results: Systemic markers such as VEGF(vascular endothelial growth factor) and OPN (Osteopontin), an early marker bone regeneration, present a peak 3 days after surgery followed by a decrease. At day 45, OPN show significant increase possibly associated with a more advanced stage of bone remodeling. The ex vivo surface analysis in the retrieval implants showed that since day 3 there was a formation of a corrosion layer with a cracked appearance. EDX results revealed that Oxygen (O), Magnesium (Mg), Phosporus (P), Calcium (Ca), and traces of alloying elements were the elements composing the corrosion layer. Moreover, the weight percent content (wt. %) of O, P and Ca increased gradually with time.
Conclusion: Our preliminary biomarkers results show a time course evolution of specific biomarkers and the pin surface analysis of explanted pins also show an increased content of O, P, Ca (wt.%) with implantation time. The use of biomarkers to assess the impact of degradable implants on the bone and whole organism is a promising starting point as a monitoring tool to follow the evolution of implant degradation and tissue regeneration.
References
[1] Zhou, H. et al., J. Magnes. Alloy. 9, 779-804 (2021).
[2] Varela, A. et al., Toxicol.Pathol. vol. 46, no. 5, pp. 511–529 (2018).
Aknowledgements This work was supported by European Training Network within the framework of Horizon 2020 Marie Skłodowska-Curie Action (MSCA) grant number No 811226.
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