title: Cytocompatibility and early inflammatory response of human endothelial cells in direct culture with Mg-Zn-Sr alloys.
abstract: Crystalline Mg-Zinc (Zn)-Strontium (Sr) ternary alloys consist of elements naturally present in the human body and provide attractive mechanical and biodegradable properties for a variety of biomedical applications. The first objective of this study was to investigate the degradation and cytocompatibility of four Mg-4Zn-xSr alloys (x=0.15, 0.5, 1.0, 1.5wt%; designated as ZSr41A, B, C, and D respectively) in the direct culture with human umbilical vein endothelial cells (HUVEC) in vitro. The second objective was to investigate, for the first time, the early-stage inflammatory response in cultured HUVECs as indicated by the induction of vascular cellular adhesion molecule-1 (VCAM-1). The results showed that the 24-h in vitro degradation of the ZSr41 alloys containing a β-phase with a Zn/Sr at% ratio ∼1.5 was significantly faster than the ZSr41 alloys with Zn/Sr at% ∼1. Additionally, the adhesion density of HUVECs in the direct culture but not in direct contact with the ZSr41 alloys for up to 24h was not adversely affected by the degradation of the alloys. Importantly, neither culture media supplemented with up to 27.6mM Mg2+ions nor media intentionally adjusted up to alkaline pH 9 induced any detectable adverse effects on HUVEC responses. In contrast, the significantly higher, yet non-cytotoxic, Zn2+ion concentration from the degradation of ZSr41D alloy was likely the cause for the initially higher VCAM-1 expression on cultured HUVECs. Lastly, analysis of the HUVEC-ZSr41 interface showed near-complete absence of cell adhesion directly on the sample surface, most likely caused by either a high local alkalinity, change in surface topography, and/or surface composition. The direct culture method used in this study was proposed as a valuable tool for studying the design aspects of Zn-containing Mg-based biomaterials in vitro, in order to engineer solutions to address current shortcomings of Mg alloys for vascular device applications.
  
  
  
  Magnesium (Mg) alloys specifically designed for biodegradable implant applications have been the focus of biomedical research since the early 2000s. Physicochemical properties of Mg alloys make these metallic biomaterials excellent candidates for temporary biodegradable implants in orthopedic and cardiovascular applications. As Mg alloys continue to be investigated for biomedical applications, it is necessary to understand whether Mg-based materials or the alloying elements have the intrinsic ability to direct an immune response to improve implant integration while avoiding cell-biomaterial interactions leading to chronic inflammation and/or foreign body reactions. The present study utilized the direct culture method to investigate for the first time the in vitro transient inflammatory activation of endothelial cells induced by the degradation products of Zn-containing Mg alloys.
authors.affiliation: Department of Bioengineering, University of California, Riverside, CA 92521, USA; Materials Science & Engineering Program, University of California, Riverside, CA 92521, USA.
authors.forename: Aaron F
authors.initials: AF
authors.lastname: Cipriano
authors.affiliation: Department of Bioengineering, University of California, Riverside, CA 92521, USA.
authors.forename: Amy
authors.initials: A
authors.lastname: Sallee
authors.affiliation: Department of Bioengineering, University of California, Riverside, CA 92521, USA.
authors.forename: Myla
authors.initials: M
authors.lastname: Tayoba
authors.affiliation: Department of Bioengineering, University of California, Riverside, CA 92521, USA.
authors.forename: Mayra C
authors.initials: MC
authors.lastname: Cortez Alcaraz
authors.affiliation: Department of Bioengineering, University of California, Riverside, CA 92521, USA.
authors.forename: Alan
authors.initials: A
authors.lastname: Lin
authors.affiliation: School of Materials and Metallurgy, Northeastern University, Shenyang 110004, China.
authors.forename: Ren-Guo
authors.initials: RG
authors.lastname: Guan
authors.affiliation: School of Materials and Metallurgy, Northeastern University, Shenyang 110004, China.
authors.forename: Zhan-Yong
authors.initials: ZY
authors.lastname: Zhao
authors.affiliation: Department of Bioengineering, University of California, Riverside, CA 92521, USA; Materials Science & Engineering Program, University of California, Riverside, CA 92521, USA; Stem Cell Center, University of California, Riverside, CA 92521, USA; Cell, Molecular and Developmental Biology Program, University of California, Riverside, CA 92521, USA. Electronic address: huinan.liu@ucr.edu.
authors.forename: Huinan
authors.initials: H
authors.lastname: Liu
mesh_terms: D000497:Alloys / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D003343:Corrosion; D003470:Culture Media; D055664:Electrochemical Techniques; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000473:pathology*; D006801:Humans; D007249:Inflammation / Q000473:pathology*; D007477:Ions; D008274:Magnesium / Q000494:pharmacology; D012995:Solubility; D013052:Spectrometry, X-Ray Emission; D013499:Surface Properties
chemical_list: D000497:Alloys; D003470:Culture Media; D007477:Ions; C573914:Mg-Zn-Sr alloy; D008274:Magnesium
keywords: Biodegradable Magnesium Zinc Strontium alloy; Biomedical implants; Early inflammatory response; Human umbilical vein endothelial cells (HUVEC); Induction of vascular cell adhesion molecule-1 (VCAM-1); Mg-Zn-Sr alloy