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Nano-copper-bearing stainless steel promotes fracture healing by accelerating the callus evolution process

Authors Wang L, Li G, Ren L, Kong X, Wang Y, Han X, Jiang W, Dai K, Yang K, Hao Y

Received 20 July 2017

Accepted for publication 17 September 2017

Published 27 November 2017 Volume 2017:12 Pages 8443—8457

DOI https://doi.org/10.2147/IJN.S146866

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Govarthanan Muthusamy

Peer reviewer comments 2

Editor who approved publication: Dr Linlin Sun


Lei Wang,1,* Guoyuan Li,1,* Ling Ren,2,* Xiangdong Kong,1 Yugang Wang,1 Xiuguo Han,1 Wenbo Jiang,3 Kerong Dai,1 Ke Yang,2 Yongqiang Hao1

1Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, 2Special Materials and Device Research Department, Institute of Metal Research, Chinese Academy of Sciences, Shenyang, 3Medical 3D Printing Innovation Research Center, Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, People’s Republic of China

*These authors contributed equally to this work

Abstract: Treatment for fractures requires internal fixation devices, which are mainly produced from stainless steel or titanium alloy without biological functions. Therefore, we developed a novel nano-copper-bearing stainless steel with nano-sized copper-precipitation (317L-Cu SS). Based on previous studies, this work explores the effect of 317L-Cu SS on fracture healing; that is, proliferation, osteogenic differentiation, osteogenesis-related gene expression, and lysyl oxidase activity of human bone mesenchymal stem cells were detected in vitro. Sprague–Dawley rats were used to build an animal fracture model, and fracture healing and callus evolution were investigated by radiology (X-ray and micro-CT), histology (H&E, Masson, and safranin O/fast green staining), and histomorphometry. Further, the Cu2+ content and Runx2 level in the callus were determined, and local mechanical test of the fracture was performed to assess the healing quality. Our results revealed that 317L-Cu SS did not affect the proliferation of human bone mesenchymal stem cells, but promoted osteogenic differentiation and the expression of osteogenesis-related genes. In addition, 317L-Cu SS upregulated the lysyl oxidase activity. The X-ray and micro-CT results showed that the callus evolution efficiency and fracture healing speed were superior for 317L-Cu SS. Histological staining displayed large amounts of fibrous tissues at 3 weeks, and cartilage and new bone at 6 weeks. Further, histomorphometric analysis indicated that the callus possessed higher osteogenic efficiency at 6 weeks, and a high Cu2+ content and increased Runx2 expression were observed in the callus for 317L-Cu SS. Besides, the mechanical strength of the fracture site was much better than that of the control group. Overall, we conclude that 317L-Cu SS possesses the ability to increase Cu2+ content and promote osteogenesis in the callus, which could accelerate the callus evolution process and bone formation to provide faster and better fracture healing.

Keywords: nano-sized copper, lysyl oxidase, osteogenesis, fracture healing, callus evolution
 

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