Theranostics 2019; 9(21):6300-6313. doi:10.7150/thno.36120

Research Paper

Copper-incorporated bioactive glass-ceramics inducing anti-inflammatory phenotype and regeneration of cartilage/bone interface

Rongcai Lin1#, Cuijun Deng2,3#, Xuxiang Li1, Yaqin Liu2, Meng Zhang2, Chen Qin2, Qingqiang Yao1✉, Liming Wang1✉, Chengtie Wu2✉

1. Department of Orthopaedics, Nanjing First Hospital, Nanjing Medical University. Nanjing 210006, P.R.China
2. State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences. Shanghai 200050, P.R.China
3. Shanghai East Hospital, the Institute for Biomedical Engineering & Nano Science, Tongji University School of Medicine, 150 Jimo Road, Shanghai 200092, P.R.China
#Rongcai Lin and Cuijun Deng are co-first authors.

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Citation:
Lin R, Deng C, Li X, Liu Y, Zhang M, Qin C, Yao Q, Wang L, Wu C. Copper-incorporated bioactive glass-ceramics inducing anti-inflammatory phenotype and regeneration of cartilage/bone interface. Theranostics 2019; 9(21):6300-6313. doi:10.7150/thno.36120. Available from http://www.thno.org/v09p6300.htm

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Abstract

Osteoarthritis not only results in cartilage lesion, but also is accompanied with subchondral bone damage caused by the inflammatory response. It is of great significance to treat osteoarthritis by regulating the immune response. As copper (Cu) plays an essential role in immune response and anti-arthritis, a copper-incorporated bioactive glass-ceramics (Cu-BGC) may achieve the aim of healing cartilage lesion and reducing inflammatory response caused by osteoarthritis. We hypothesized that the Cu2+ released from Cu-BGC scaffolds may satisfy the requirements of cartilage regeneration and anti-arthritis.

Methods: 3D-printing method was employed to prepare Cu-BGC scaffolds. The stimulating effect on the chondrocytes and macrophages cultured with Cu-BGC extracts was investigated. Furthermore, the in vivo regenerative effect of Cu-BGC scaffolds on osteochondral defects was studied.

Results: The incorporation of Cu2+ into BGC considerably promoted the proliferation and maturation of chondrocytes, and induced macrophages shifting to anti-inflammatory phenotype. Histological analysis demonstrated that the Cu-BGC scaffolds meaningfully improved the regeneration of cartilage and elevated the recovery of the osteochondral interface as compared with the CTR and BGC groups. The potential mechanism is related to Cu2+ ions triggering the immune response of cartilage via activating HIF signaling pathway and inhibiting the inflammatory response in osteochondral tissue.

Conclusion: These results demonstrated that Cu-BGC scaffolds significantly facilitated the regeneration of cartilage and osteochondral interface, as well as inhibited inflammatory response, which may prevent the development of osteoarthritis associated with osteochondral defects.

Keywords: copper, bioactive glass ceramics, osteoarthritis, cartilage regeneration, immunomodulation