title: Ex vivo blood vessel bioreactor for analysis of the biodegradation of magnesium stent models with and without vessel wall integration.
abstract: Current in vitro models fail in predicting the degradation rate and mode of magnesium (Mg) stents in vivo. To overcome this, the microenvironment of the stent is simulated here in an ex vivo bioreactor with porcine aorta and circulating medium, and compared with standard static in vitro immersion and with in vivo rat aorta models. In ex vivo and in vivo conditions, pure Mg wires were exposed to the aortic lumen and inserted into the aortic wall to mimic early- and long-term implantation, respectively. Results showed that: 1) Degradation rates of Mg were similar for all the fluid diffusion conditions (in vitro static, aortic wall ex vivo and in vivo); however, Mg degradation under flow condition (i.e. in the lumen) in vivo was slower than ex vivo; 2) The corrosion mode in the samples can be mainly described as localized (in vitro), mixed localized and uniform (ex vivo), and uniform (in vivo); 3) Abundant degradation products (MgO/Mg(OH)2and Ca/P) with gas bubbles accumulated around the localized degradation regions ex vivo, but a uniform and thin degradation product layer was found in vivo. It is concluded that the ex vivo vascular bioreactor provides an improved test setting for magnesium degradation between static immersion and animal experiments and highlights its promising role in bridging degradation behavior and biological response for vascular stent research.
  
  
  
  Magnesium and its alloys are candidates for a new generation of biodegradable stent materials. However, the in vitro degradation of magnesium stents does not match the clinical degradation rates, corrupting the validity of conventional degradation tests. Here we report an ex vivo vascular bioreactor, which allows simulation of the microenvironment with and without blood vessel integration to study the biodegradation of magnesium implants in comparison with standard in vitro test conditions and with in vivo implantations. The bioreactor did simulate the corrosion of an intramural implant very well, but showed too high degradation for non-covered implants. It is concluded that this system is in between static incubation and animal experiments concerning the predictivity of the degradation.
authors.affiliation: NSF Engineering Research Center for Revolutionizing Metallic Biomaterials, North Carolina A&T State University, Greensboro, NC 27411, USA; Key Laboratory of Advanced Technologies of Materials, Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu, Sichuan 610031, PR China.
authors.forename: Juan
authors.initials: J
authors.lastname: Wang
authors.affiliation: NSF Engineering Research Center for Revolutionizing Metallic Biomaterials, North Carolina A&T State University, Greensboro, NC 27411, USA; FIT BEST Laboratory, Department of Chemical, Biological, and Bio Engineering, North Carolina A&T State University, Greensboro, NC 27411, USA.
authors.forename: Lumei
authors.initials: L
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, Nankai University, Tianjin 300071, PR China.
authors.forename: Yifan
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Leibniz Institute of Polymer Research Dresden, Max Bergmann Center of Biomaterials Dresden, Dresden 01069, Germany.
authors.forename: Manfred F
authors.initials: MF
authors.lastname: Maitz
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, Nankai University, Tianjin 300071, PR China.
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Wang
authors.affiliation: NSF Engineering Research Center for Revolutionizing Metallic Biomaterials, North Carolina A&T State University, Greensboro, NC 27411, USA; FIT BEST Laboratory, Department of Chemical, Biological, and Bio Engineering, North Carolina A&T State University, Greensboro, NC 27411, USA.
authors.forename: Youngmi
authors.initials: Y
authors.lastname: Koo
authors.affiliation: Key Laboratory of Advanced Technologies of Materials, Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu, Sichuan 610031, PR China.
authors.forename: Ansha
authors.initials: A
authors.lastname: Zhao
authors.affiliation: NSF Engineering Research Center for Revolutionizing Metallic Biomaterials, North Carolina A&T State University, Greensboro, NC 27411, USA; FIT BEST Laboratory, Department of Chemical, Biological, and Bio Engineering, North Carolina A&T State University, Greensboro, NC 27411, USA.
authors.forename: Jagannathan
authors.initials: J
authors.lastname: Sankar
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, Nankai University, Tianjin 300071, PR China. Electronic address: kongdeling@nankai.edu.cn.
authors.forename: Deling
authors.initials: D
authors.lastname: Kong
authors.affiliation: Key Laboratory of Advanced Technologies of Materials, Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu, Sichuan 610031, PR China. Electronic address: huangnan1956@163.com.
authors.forename: Nan
authors.initials: N
authors.lastname: Huang
authors.affiliation: NSF Engineering Research Center for Revolutionizing Metallic Biomaterials, North Carolina A&T State University, Greensboro, NC 27411, USA; FIT BEST Laboratory, Department of Chemical, Biological, and Bio Engineering, North Carolina A&T State University, Greensboro, NC 27411, USA. Electronic address: yyun@ncat.edu.
authors.forename: Yeoheung
authors.initials: Y
authors.lastname: Yun
mesh_terms: D020341:Absorbable Implants; D000818:Animals; D019149:Bioreactors; D001807:Blood Vessel Prosthesis; D005260:Female; D008274:Magnesium / Q000737:chemistry*; D019919:Prosthesis Implantation; D017207:Rats, Sprague-Dawley; D013052:Spectrometry, X-Ray Emission; D013194:Staining and Labeling; D015607:Stents; D034421:Sus scrofa; D055114:X-Ray Microtomography
chemical_list: D008274:Magnesium
keywords: Biodegradation; Ex vivo; In vitro; In vivo; Magnesium; Vascular bioreactor