Molecular mechanisms of osteogenesis and antibacterial activity of Cu-bearing Ti alloy in a bone defect model with infection in vivo

doi:10.1016/j.jot.2020.10.004

CORC > 金属研究所 > 中国科学院金属研究所

	Molecular mechanisms of osteogenesis and antibacterial activity of Cu-bearing Ti alloy in a bone defect model with infection in vivo
	Yang, Jun 1,3; Qin, Hanjun 1; Chai, Yu 1; Zhang, Ping 1; Chen, Yirong 1; Yang, Ke 2; Qin, Min 4; Zhang, Yifang 5; Xia, Hong 3; Ren, Ling 2
刊名	JOURNAL OF ORTHOPAEDIC TRANSLATION
	2021-03-01
卷号	27 页码:77-89
关键词	Antibacterial Bone defect isobaric tags for relative and absolute quantification(iTRAQ) analysis Osteogenesis Ti6Al4V-6.5wt%Cu alloy
ISSN号	2214-031X
DOI	10.1016/j.jot.2020.10.004
通讯作者	Xia, Hong(gzxiahong2@126.com) ; Ren, Ling(lren@imr.ac.cn) ; Yu, Bin(yubin@smu.edu.cn)
英文摘要	Objective: The antibacterial activity of copper (Cu)-alloy biomaterials has shown a great potential in clinical application. Here, we evaluated the osteogenesis and antibacterial effects of Ti6Al4V-6.5wt%Cu alloy in an in vivo model of infected bone defects and determine their responsible proteins and pathways using proteomics. Methods: After bone defects were filled with Ti6Al4V and Ti6Al4V-6.5wt%Cu implants for 6 week, the tissue and bone samples around the implants were harvested for radiographic, micro-CT, histological, and bone-related gene expression analyses. An iTRAQ-based protein identification/quantification approach was used to analyze the osteogenic and antibacterial effects of Ti6Al4V-6.5wt%Cu alloy. Results: Imaging and histological results showed Ti6Al4V alloy induced a stronger inflammatory response than Ti6Al4V-6.5wt%Cu alloy; imaging results and osteogenic protein levels showed Ti6Al4V-6.5wt%Cu alloy exerted a stronger osteogenic effect. In vitro experiment, we found the Ti6Al4V-6.5wt%Cu had significant antibacterial effects and inhibited the activity of Staphylococcus aureus in the early stage. In addition, the bacterial biofilm formed in Ti6Al4V-6.5wt%Cu group was significantly lower than that in Ti6Al4V group. Proteomic screening of 4279 proteins resulted in 35 differentially expressed proteins for further examination which were mainly associated with the cellular process, metabolic process, stimulus response, and cellular component organization. In further exploration of the mechanism of osteogenic mineralization of Ti6Al4V-6.5wt%Cu alloy, we found out SDC4 and AGRN were the top two target proteins associated with osteogenic differentiation and bone mineralization. Conclusion: Ti6Al4V-6.5wt%Cu alloy shows a great potential as a bone implant material due to its positive effects against bacterial infection and on bone formation. The Translational potential of this article: At present, titanium alloys and other non-antibacterial metal materials are used in orthopedic internal fixation operations. Our study demonstrates that Ti6Al4V-6.5wt%Cu alloy has good antibacterial and osteogenic effects in vivo and in vitro. This means that Ti6Al4V-6.5wt%Cu alloy may become a new kind of antimicrobial metallic material as internal fixation material to continuously exert its antimicrobial effects and reduce the infection rate after clinical internal fixation.
资助项目	Medical Technique and Research Program of Guangdong Province, China[A2017463] ; China Postdoctoral Science Foundation, China[2017M613432] ; Youth Training Program for Military Medical Science and Technology[19QNP005] ; Guangdong Medical Science And Technology Research Foundation[2016102511210492] ; National Key Research and Development Program of China[2018YFC1106601] ; Promoting Liaoning Province Talents Program - Top Young Talents[XLYC1807069]
WOS研究方向	Orthopedics
语种	英语
出版者	ELSEVIER
WOS记录号	WOS:000637527900012
资助机构	Medical Technique and Research Program of Guangdong Province, China ; China Postdoctoral Science Foundation, China ; Youth Training Program for Military Medical Science and Technology ; Guangdong Medical Science And Technology Research Foundation ; National Key Research and Development Program of China ; Promoting Liaoning Province Talents Program - Top Young Talents
内容类型	期刊论文
源URL	[http://ir.imr.ac.cn/handle/321006/162101]
专题	金属研究所_中国科学院金属研究所
通讯作者	Xia, Hong; Ren, Ling; Yu, Bin
作者单位	1.Southern Med Univ, Guangdong Prov Key Lab Bone & Cartilage Regenerat, Nanfang Hosp, Dept Orthopaed, Guangzhou 510515, Guangdong, Peoples R China 2.Chinese Acad Sci, Inst Met Res, Shenyang 110016, Peoples R China 3.Guangzhou Mil Command PLA, Guangdong Key Lab Orthopaed Technol & Implant Mat, Key Lab Trauma & Tissue Repair Trop Area PLA, Dept Orthopaed,Guangzhou Gen Hosp, Guangzhou 510010, Peoples R China 4.Southern Med Univ, Sch Publ Hlth, Expt Teaching Ctr Prevent Med, Guangzhou 510515, Guangdong, Peoples R China 5.Southern Med Univ, Nanfang Hosp, Chinese Journal Orthopaed Trauma, Editorial Off, Guangzhou 510515, Guangdong, Peoples R China
推荐引用方式 GB/T 7714	Yang, Jun,Qin, Hanjun,Chai, Yu,et al. Molecular mechanisms of osteogenesis and antibacterial activity of Cu-bearing Ti alloy in a bone defect model with infection in vivo[J]. JOURNAL OF ORTHOPAEDIC TRANSLATION,2021,27:77-89.
APA	Yang, Jun.,Qin, Hanjun.,Chai, Yu.,Zhang, Ping.,Chen, Yirong.,...&Yu, Bin.(2021).Molecular mechanisms of osteogenesis and antibacterial activity of Cu-bearing Ti alloy in a bone defect model with infection in vivo.JOURNAL OF ORTHOPAEDIC TRANSLATION,27,77-89.
MLA	Yang, Jun,et al."Molecular mechanisms of osteogenesis and antibacterial activity of Cu-bearing Ti alloy in a bone defect model with infection in vivo".JOURNAL OF ORTHOPAEDIC TRANSLATION 27(2021):77-89.