Biodegradable Mg-Cu alloy implants with antibacterial activity for the treatment of osteomyelitis: In vitro and in vivo evaluations

被引:241
作者
Li, Yang [1 ]
Liu, Lina [2 ]
Wan, Peng [3 ]
Zhai, Zanjing [1 ]
Mao, Zhenyang [1 ]
Ouyang, Zhengxiao [1 ]
Yu, Degang [1 ]
Sun, Qi [4 ]
Tan, Lili [3 ]
Ren, Ling [3 ]
Zhu, Zhenan [1 ]
Hao, Yongqiang [1 ]
Qu, Xinhua [1 ]
Yang, Ke [3 ]
Dai, Kerong [1 ]
机构
[1] Shanghai Jiao Tong Univ, Shanghai Peoples Hosp 9, Dept Orthopaed Surg, Shanghai Key Lab Orthopaed Implants,Sch Med, 639 Zhizaoju Rd, Shanghai 200011, Peoples R China
[2] Shanghai Jiao Tong Univ, Shanghai Peoples Hosp 9, Dept Plast & Reconstruct Surg, Sch Med, Shanghai, Peoples R China
[3] Chinese Acad Sci, Inst Met Res, 72 Wenhua Rd, Shenyang 110016, Peoples R China
[4] Shanghai Jiao Tong Univ, Sch Med, Shanghai Peoples Hosp 9, Dept Radiol, Shanghai, Peoples R China
基金
中国国家自然科学基金; 上海市自然科学基金;
关键词
Osteomyelitis; Antibacterial activity; Biodegradable; Mg-Cu alloy; STAPHYLOCOCCUS-AUREUS; PSEUDOMONAS-AERUGINOSA; CORROSION-RESISTANCE; BIOFILM FORMATION; STAINLESS-STEEL; CHARGE-TRANSFER; RABBIT MODEL; LOADED PMMA; COPPER; TITANIUM;
D O I
10.1016/j.biomaterials.2016.08.031
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
Treatment of chronic osteomyelitis (bone infection) remains a clinical challenge; in particular, it requires an implantable material with improved antibacterial activity. Here, we prepared biodegradable magnesium (Mg)-copper (Cu) alloys with different Cu contents (0.05, 0.1, and 0.25 wt%) and assessed their potential for treating methicillin-resistant Staphylococcus aureus-induced osteomyelitis. We evaluated the microstructures, mechanical properties, corrosion behavior, and ion release of the alloys in vitro, and their biocompatibility and antibacterial activity in vitro and in vivo. The antibacterial activity of the Mg Cu alloys in vitro was demonstrated by microbiological counting assays, bacterial viability assays, biofilm formation observations, and the expression of biofilm, virulence, and antibiotic-resistance associated genes. The antibacterial activity of Mg-Cu alloys in vivo was confirmed by imaging examination, microbiological cultures, and histopathology. The biocompatibility of Mg-Cu alloys was confirmed by cell proliferation, vitality, and morphology assays in vitro and Cu2+ or Mg2+ ion assays, blood biochemical tests, and histological evaluation in vivo. The alloy containing 0.25 wt% Cu exhibited the highest antibacterial activity among the tested alloys, with favorable biocompatibility. Collectively, our results indicate the potential utility of Mg -Cu alloy implants with 0.25 wt% Cu in treating orthopedic infections. (C) 2016 Elsevier Ltd. All rights reserved.
引用
收藏
页码:250 / 263
页数:14
相关论文
共 75 条
[1]   Bactericidal activity of copper and niobium-alloyed austenitic stainless steel [J].
Baena, M. I. ;
Marquez, M. C. ;
Matres, V. ;
Botella, J. ;
Ventosa, A. .
CURRENT MICROBIOLOGY, 2006, 53 (06) :491-495
[2]   2015 Infectious Diseases Society of America (IDSA) Clinical Practice Guidelines for the Diagnosis and Treatment of Native Vertebral Osteomyelitis in Adultsa [J].
Berbari, Elie F. ;
Kanj, Souha S. ;
Kowalski, Todd J. ;
Darouiche, Rabih O. ;
Widmer, Andreas F. ;
Schmitt, Steven K. ;
Hendershot, Edward F. ;
Holtom, Paul D. ;
Huddleston, Paul M. ;
Petermann, Gregory W. ;
Osmon, Douglas R. .
CLINICAL INFECTIOUS DISEASES, 2015, 61 (06) :E26-E46
[3]   Sonication is superior to scraping for retrieval of bacteria in biofilm on titanium and steel surfaces in vitro [J].
Bjerkan, Geir ;
Witso, Eivind ;
Bergh, Kare .
ACTA ORTHOPAEDICA, 2009, 80 (02) :245-250
[4]   MRSA prevention strategies and current guidelines [J].
Byrne, F. M. ;
Wilcox, M. H. .
INJURY-INTERNATIONAL JOURNAL OF THE CARE OF THE INJURED, 2011, 42 :S3-S6
[5]   Antibacterial effect of 317L stainless steel contained copper in prevention of implant-related infection in vitro and in vivo [J].
Chai, Hongwei ;
Guo, Lei ;
Wang, Xiantao ;
Fu, Yuping ;
Guan, Junlin ;
Tan, Lili ;
Ren, Ling ;
Yang, Ke .
JOURNAL OF MATERIALS SCIENCE-MATERIALS IN MEDICINE, 2011, 22 (11) :2525-2535
[6]   Efficacy of antibiotics-loaded interpenetrating network (IPNs) hydrogel based on poly(acrylic acid) and gelatin for treatment of experimental osteomyelitis: in vivo study [J].
Changez, M ;
Koul, V ;
Dinda, AK .
BIOMATERIALS, 2005, 26 (14) :2095-2104
[7]   High-purity magnesium interference screws promote fibrocartilaginous entheses regeneration in the anterior cruciate ligament reconstruction rabbit model via accumulation of BMP-2 and VEGF [J].
Cheng, Pengfei ;
Han, Pei ;
Zhao, Changli ;
Zhang, Shaoxiang ;
Wu, Hongliu ;
Ni, Jiahua ;
Hou, Peng ;
Zhang, Yuanzhuang ;
Liu, Jingyi ;
Xu, Haidong ;
Liu, Shen ;
Zhang, Xiaonong ;
Zheng, Yufeng ;
Chai, Yimin .
BIOMATERIALS, 2016, 81 :14-26
[8]  
COLANGELO V J, 1967, Journal of Biomedical Materials Research, V1, P405, DOI 10.1002/jbm.820010405
[9]   Effects of erythromycin on the phenotypic and genotypic biofilm expression in two clinical Staphylococcus capitis subspecies and a functional analysis of Ica proteins in S. capitis [J].
Cui, Bintao ;
Smooker, Peter M. ;
Rouch, Duncan A. ;
Deighton, Margaret A. .
JOURNAL OF MEDICAL MICROBIOLOGY, 2015, 64 :591-604
[10]  
DEIRMENGIAN CA, 2016, CLIN ORTHOP RELAT RE