title: In vivo characterization of magnesium alloy biodegradation using electrochemical H2monitoring, ICP-MS, and XPS.
abstract: The effect of widely different corrosion rates of Mg alloys on four parameters of interest for in vivo characterization was evaluated: (1) the effectiveness of transdermal H2measurements with an electrochemical sensor for noninvasively monitoring biodegradation compared to the standard techniques of in vivo X-ray imaging and weight loss measurement of explanted samples, (2) the chemical compositions of the corrosion layers of the explanted samples by XPS, (3) the effect on animal organs by histology, and (4) the accumulation of corrosion by-products in multiple organs by ICP-MS. The in vivo biodegradation of three magnesium alloys chosen for their widely varying corrosion rates - ZJ41 (fast), WKX41 (intermediate) and AZ31 (slow) - were evaluated in a subcutaneous implant mouse model. Measuring H2with an electrochemical H2sensor is a simple and effective method to monitor the biodegradation process in vivo by sensing H2transdermally above magnesium alloys implanted subcutaneously in mice. The correlation of H2levels and biodegradation rate measured by weight loss shows that this non-invasive method is fast, reliable and accurate. Analysis of the insoluble biodegradation products on the explanted alloys by XPS showed all of them to consist primarily of Mg(OH)2, MgO, MgCO3and Mg3(PO4)2with ZJ41 also having ZnO. The accumulation of magnesium and zinc were measured in 9 different organs by ICP-MS. Histological and ICP-MS studies reveal that there is no significant accumulation of magnesium in these organs for all three alloys; however, zinc accumulation in intestine, kidney and lung for the faster biodegrading alloy ZJ41 was observed. Although zinc accumulates in these three organs, no toxicity response was observed in the histological study. ICP-MS also shows higher levels of magnesium and zinc in the skull than in the other organs.
  
  
  
  Biodegradable devices based on magnesium and its alloys are promising because they gradually dissolve and thereby avoid the need for subsequent removal by surgery if complications arise. In vivo biodegradation rate is one of the crucial parameters for the development of these alloys. Promising alloys are first evaluated in vivo by being implanted subcutaneously in mice for 1month. Here, we evaluated several magnesium alloys with widely varying corrosion rates in vivo using multiple characterization techniques. Since the alloys biodegrade by reacting with water forming H2gas, we used a recently demonstrated, simple, fast and noninvasive method to monitor the biodegradation process by just pressing the tip of a H2sensor against the skin above the implant. The analysis of 9 organs (intestine, kidney, spleen, lung, heart, liver, skin, brain and skull) for accumulation of Mg and Zn revealed no significant accumulation of magnesium in these organs. Zinc accumulation in intestine, kidney and lung was observed for the faster corroding implant ZJ41. The surfaces of explanted alloys were analyzed to determine the composition of the insoluble biodegradation products. The results suggest that these tested alloys are potential candidates for biodegradable implant applications.
authors.affiliation: Department of Chemistry, University of Cincinnati, Cincinnati, OH 45221, USA.
authors.forename: Daoli
authors.initials: D
authors.lastname: Zhao
authors.affiliation: Department of Chemistry, University of Cincinnati, Cincinnati, OH 45221, USA.
authors.forename: Tingting
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Chemistry, University of Cincinnati, Cincinnati, OH 45221, USA.
authors.forename: Keaton
authors.initials: K
authors.lastname: Nahan
authors.affiliation: Medpace, Bioanalytical Laboratories, Cincinnati, OH 45227, USA.
authors.forename: Xuefei
authors.initials: X
authors.lastname: Guo
authors.affiliation: Procter and Gamble, Cincinnati, OH 45232, USA.
authors.forename: Zhanping
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Internal Medicine, University of Cincinnati, Cincinnati, OH 45267, USA.
authors.forename: Zhongyun
authors.initials: Z
authors.lastname: Dong
authors.affiliation: Department of Internal Medicine, University of Cincinnati, Cincinnati, OH 45267, USA.
authors.forename: Shuna
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15261, USA.
authors.forename: Da-Tren
authors.initials: DT
authors.lastname: Chou
authors.affiliation: Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15261, USA.
authors.forename: Daeho
authors.initials: D
authors.lastname: Hong
authors.affiliation: Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15261, USA; Department of Chemical and Petroleum Engineering, University of Pittsburgh, Pittsburgh, PA 15261, USA; Department of Mechanical Engineering and Materials Science, University of Pittsburgh, Pittsburgh, PA 15261, USA.
authors.forename: Prashant N
authors.initials: PN
authors.lastname: Kumta
authors.affiliation: Department of Chemistry, University of Cincinnati, Cincinnati, OH 45221, USA. Electronic address: William.Heineman@uc.edu.
authors.forename: William R
authors.initials: WR
authors.lastname: Heineman
mesh_terms: D020341:Absorbable Implants; D000497:Alloys / Q000737:chemistry*; D000818:Animals; D055664:Electrochemical Techniques / Q000379:methods*; D006859:Hydrogen / Q000032:analysis*; D008274:Magnesium / Q000737:chemistry*; D008819:Mice, Nude; D056951:Photoelectron Spectroscopy; D013054:Spectrophotometry, Atomic; D014018:Tissue Distribution; D014965:X-Rays; D015032:Zinc / Q000032:analysis
chemical_list: D000497:Alloys; D006859:Hydrogen; D008274:Magnesium; D015032:Zinc
keywords: Biodegradable implants; Hydrogen; Hydrogen sensor; Magnesium; Magnesium alloys; Metallic trace; Zinc