Results of In Vivo Biological Tests Performed on a Mg-0.8Ca Alloy

Abstract:

Biodegradable magnesium-based alloys shows good prospects in their use as biodegradable orthopedic materials. The aim of this study is to demonstrate good biocompatibility and lack of local and systemic toxicity of some experimental implants made by magnesium alloy type Mg-Ca 0,8 [%wt]. The study was conducted by implanting some experimental pins made by magnesium alloy type Mg-Ca 0,8 [%wt] in bone, proximal femur and intramedullary tibia, and in thigh muscle of the rabbits. Also, we follow the evolution of blood levels of Mg, Ca, blood counts, liver and kidney function. The evolution of the experience animals was followed for 6 weeks by radiologic imaging, and taking blood samples. After 6 weeks, we obtain after euthanasia of animal experience the harvest blood samples, and musculoskeletal tissue samples for histopathological examination. The histopathology results have not demonstrated peri-implant cytotoxicity, bone and muscle cells being viable. Fibrosis at tissue implant border was minimal showing a good integration. There were no pathological increases in blood levels of Mg and Ca, or changes in blood counts, as well as no change in renal or hepatic function. All this experimental results demonstrates that the magnesium alloy type Mg-Ca 0,8 [%wt] represent a promising solution in orthopedic surgery, proving to be safe, with a high degree of biocompatibility, and without toxic effects.

• Periodical: Key Engineering Materials (Volume 745)
• Pages: 50-61
• DOI: https://doi.org/10.4028/www.scientific.net/KEM.745.50
• Online since: July 2017
• Authors: Razvan Adam*, Horia Orban, Elisa Plopeanu, Dan Voinescu, Adrian Barbilian
• Keywords: Biocompatibility, Histology, In Vivo Testing, Magnesium Alloys, Orthopedic Implant

References

[1] Witte F., The history of biodegradable magnesium implants: A review, Acta Biomaterialia, 6 (2010) 1680–1692.

DOI: 10.1016/j.actbio.2010.02.028

[2] Antoniac I., Handbook of Bioceramics and Biocomposites, Springer International Publishing, New York (2016) 935-967.

[3] Saris N.E., Mervaala E., Karppanen H., Khawaja J.A., Lewenstam A., Magnesium. An update on physiological, clinical and analytical aspects, Clin Chim Acta, 294 (2000) 1-26.

DOI: 10.1016/s0009-8981(99)00258-2

[4] Rude R.K., Magnesium metabolism and deficiency, Endocrinol Metab Clin North Am, 22 (1993) 377-395.

[5] Fox C., Ramsoomair D., Carter C., Magnesium: its proven and potential clinical significance, South Med J, 94 (2001) 1195-1201.

DOI: 10.1097/00007611-200194120-00014

[6] Razavi M., Fathi M.H., Meratian M., Microstructure, mechanical properties and bio-corrosion evaluation of biodegradable AZ91-FA nanocomposites for biomedical applications, Materials science and engineering: A, 527 (2010) 6938-6944.

DOI: 10.1016/j.msea.2010.07.063

[7] Cha P.R., Han H.S., Yang G.F., Seok H.K., Biodegradability engineering of biodegradable Mg alloys: Tailoring the electrochemical properties and microstructure of constituent phases, Scientific Reports, 3: 2367 (2013) 1-6.

DOI: 10.1038/srep02367

[8] Gu X., Zheng Y., Cheng Y., Zhong S., Xi T., In vitro corrosion and biocompatibility of binary magnesium alloys, Biomaterials, 30 (2009) 484-498.

DOI: 10.1016/j.biomaterials.2008.10.021

[9] Zheng Y.F., Gu X.N., Witte F., Biodegradable metals, Materials Science and Engineering: R: Reports, 77 (2014) 1-34.

[10] Gu X.N., Zheng Y.F., A review on magnesium alloys as biodegradable materials, Frontiers of Materials Science in China, 4 (2010) 111-115.

[11] Zeng R., Dietzel W., Witte F., Hort N., Blawert C., Progress and challenge for magnesium alloys as biomaterials, Adv Eng Mater, 10 (2008) B3–B14.

DOI: 10.1002/adem.200800035

[12] Antoniac I., Miculescu M., Dinu M., Metallurgical characterization of some magnesium alloys for medical applications, Solid State Phenomena, 188 (2012) 109-113.

DOI: 10.4028/www.scientific.net/ssp.188.109

[13] Zhang S., Zhang X., Zhao C., Li J., Song Y., Xie C., Research on an Mg–Zn alloy as a degradable biomaterial, Acta Biomater, 6 (2010) 626–640.

DOI: 10.1016/j.actbio.2009.06.028

[14] Zhang X.B., Yuan G.Y., Niu J.L., Fu P.H., Ding W.J., Microstructure, mechanical properties, biocorrosion behavior, and cytotoxicity of as-extruded Mg–Nd–Zn–Zr alloy with different extrusion ratios, J Mech Behav Biomed Mater, 9 (2012) 153–162.

DOI: 10.1016/j.jmbbm.2012.02.002

[15] Peuster M., Wohlsein P., Brugmann M., Ehlerding M., Seidler K., Fink C., A novel approach to temporary stenting: degradable cardiovascular stents produced from corrodible metal – results 6–18 months after implantation into New Zealand white rabbits, Heart, 86 (2001).

DOI: 10.1136/heart.86.5.563

[16] Blawert C., Dietzel W., Ghali E., Song G., Anodizing treatments for magnesium alloys and their effect on corrosion resistance in various environments, Adv Eng Mater, 8 (2006) 511–533.

DOI: 10.1002/adem.200500257

[17] Hornberger H., Virtanen S., Boccaccini A.R., Biomedical coatings on magnesium alloys–A review, Acta Biomaterialia, 8 (2012) 2442–2455.

DOI: 10.1016/j.actbio.2012.04.012

[18] Lorenz C., Brunner J.G., Kollmannsberger P., Jaafar L., Fabry B., Virtanen S., Effect of surface pre-treatments on biocompatibility of magnesium, Acta Biomater, 5 (2009) 2783–2789.

DOI: 10.1016/j.actbio.2009.04.018

[19] Antoniac I., Vranceanu M.D., Antoniac A., The influence of the magnesium powder used as reinforcement material on the properties of some collagen based composite biomaterials, JOAM, 15 (2013) 667-672.

[20] Witte F., Kaese V., Haferkamp H., Switzer E., Meyer-Lindenberg A., Wirth C., In vivo corrosion of four magnesium alloys and the associated bone response, Biomaterials, 26 (2005) 3557–3563.

DOI: 10.1016/j.biomaterials.2004.09.049

[21] Li N., Zheng Y., Novel Magnesium Alloys Developed for Biomedical Application: A Review, J. Mater. Sci. Technol., 29 (2013) 489-502.

[22] Trumbo P., Schlicker S., Yates A.A., Poos M., Dietary reference intakes for energy, carbohydrate, fiber, fat, fatty acids, cholesterol, protein and amino acids, J Am Diet Assoc, 102 (2002) 1621–1630.

DOI: 10.1016/s0002-8223(02)90346-9

[23] Feser K., Kietzmann M., Baumer W., Krause C., Bach F.W., Effects of degradable Mg-Ca alloys on dendritic cell function, J. Biomater. Appl., 25 (2011) 685–697.

DOI: 10.1177/0885328209360424

[24] Li Z.J., Gu X.N., Lou S.Q., Zheng Y.F., The development of binary Mg–Ca alloys for use as biodegradable materials within bone, Biomaterials, 29 (2008) 1329–1344.

DOI: 10.1016/j.biomaterials.2007.12.021

[25] Thomann M., Krause C., Bormann D., von der Hoh N., Windhagen H., Meyer-Lindenberg A., Comparison of the resorbable magnesium alloys LAE442 und MgCa0. 8 concerning their mechanical properties, their progress of degradation and the bone-implant contact after 12 months implantation duration in a rabbit model, Materialwiss. Werkst., 40 (2009).

DOI: 10.1002/mawe.200800412

[26] Antoniac I.V., Miculescu M., Dinu M., Metallurgical characterization of some magnesium alloys for medical applications, Solid State Phenomena, 188 (2012) 109-113.

DOI: 10.4028/www.scientific.net/ssp.188.109

[27] Blajan A.I., Miculescu F., Ciuca I., Cotrut C., Semenescu A., Antoniac I., Effect of Calcium Content on the Microstructure and Degradation of Mg-Ca Binary Alloys potentially used as Orthopedic Biomaterials, KEM, 638 (2014) 104-108.

DOI: 10.4028/www.scientific.net/kem.638.104

[28] Mareci D., Bolat G., Izquierdo J., Crimu C., Munteanu C., Antoniac I., Souto R.M., Electrochemical characteristics of bioresorbable binary MgCa alloys in Ringer's solution: Revealing the impact of local pH distributions during in-vitro dissolution, Materials Science and Engineering: C, 60 (2016).

DOI: 10.1016/j.msec.2015.11.069

[29] Bita A.I., Stan G.E., Niculescu M., Ciuca I., Vasile E., Antoniac I., Adhesion evaluation of different bioceramic coatings on Mg–Ca alloys for biomedical applications, JAST 30 (2016) 1968-(1983).

DOI: 10.1080/01694243.2016.1171569

[30] Rau J.V., Antoniac I., Fosca M., De Bonis A., Blajan A.I., Cotrut C., Graziani V., Curcio M., Cricenti A., Niculescu M., Ortenzi M., Teghil R., Glass-ceramic coated Mg-Ca alloys for biomedical implant applications, Materials Science and Engineering: C, 64 (2016).

DOI: 10.1016/j.msec.2016.03.100

[31] Bita A.I., Antoniac A., Cotrut C., Vasile E., Ciuca I., Niculescu M., Antoniac I., In vitro Degradation and Corrosion Evaluation of Mg-Ca Alloys for Biomedical Applications, JOAM, 18 (2016) 394-398.

DOI: 10.1080/01694243.2016.1171569