期刊
THERANOSTICS
卷 9, 期 21, 页码 6300-6313出版社
IVYSPRING INT PUBL
DOI: 10.7150/thno.36120
关键词
copper; bioactive glass ceramics; osteoarthritis; cartilage regeneration; immunomodulation
资金
- National Key Research and Development Program of China [2018YFC1105201/204]
- National Natural Science Foundation of China [5171101275, 81771985]
- Shanghai Nature Science Foundation [19ZR1464800]
- Key Research Program of Science & Technology Support Program of Jiangsu Province [BE2016763]
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.
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