Functionalized TiCu/TiCuN Coating Promotes Osteoporotic Fracture Healing by Upregulating the Wnt/β-catenin Pathway

Overview

Journal Regen Biomater

Specialty Biomedical Engineering

Date 2023 Jan 23

PMID 36683750

Authors

Jia Tan

Ling Ren

Kai Xie

Lei Wang

Wenbo Jiang

Yu Guo

Yongqiang Hao

Affiliations

Soon will be listed here.

Abstract

Osteoporosis results in decreased bone mass and insufficient osteogenic function. Existing titanium alloy implants have insufficient osteoinductivity and delayed/incomplete fracture union can occur when used to treat osteoporotic fractures. Copper ions have good osteogenic activity, but their dose-dependent cytotoxicity limits their clinical use for bone implants. In this study, titanium alloy implants functionalized with a TiCu/TiCuN coating by arc ion plating achieved a controlled release of copper ions for 28 days. The coated alloy was co-cultured with bone marrow mesenchymal stem cells and showed excellent biocompatibility and osteoinductivity . A further exploration of the underlying mechanism by quantitative real-time polymerase chain reaction and western blotting revealed that the enhancement effects are related to the upregulation of genes and proteins (such as axin2, β-catenin, GSK-3β, p-GSK-3β, LEF1 and TCF1/TCF7) involved in the Wnt/β-catenin pathway. experiments showed that the TiCu/TiCuN coating significantly promoted osteoporotic fracture healing in a rat femur fracture model, and has good biocompatibility based on various staining results. Our study confirmed that TiCu/TiCuN-coated Ti promotes osteoporotic fracture healing associated with the Wnt pathway. Because the coating effectively accelerates the healing of osteoporotic fractures and improves bone quality, it has significant clinical application prospects.

Citing Articles

Copper metabolism in osteoarthritis and its relation to oxidative stress and ferroptosis in chondrocytes.

Yu Q, Xiao Y, Guan M, Zhang X, Yu J, Han M Front Mol Biosci. 2024; 11:1472492.

PMID: 39329090 PMC: 11425083. DOI: 10.3389/fmolb.2024.1472492.

Fibrous topology promoted pBMP2-activated matrix on titanium implants boost osseointegration.

He T, Wang Y, Wang R, Yang H, Hu X, Pu Y Regen Biomater. 2024; 11:rbad111.

PMID: 38173764 PMC: 10761207. DOI: 10.1093/rb/rbad111.

Carnosine, Zinc and Copper: A Menage a Trois in Bone and Cartilage Protection.

Ciaffaglione V, Rizzarelli E Int J Mol Sci. 2023; 24(22).

PMID: 38003398 PMC: 10671046. DOI: 10.3390/ijms242216209.

References

Bao Q, Chen S, Qin H, Feng J, Liu H, Liu D . An appropriate Wnt/β-catenin expression level during the remodeling phase is required for improved bone fracture healing in mice. Sci Rep. 2017; 7(1):2695. PMC: 5457421. DOI: 10.1038/s41598-017-02705-0. View

Su Y, Cockerill I, Zheng Y, Tang L, Qin Y, Zhu D . Biofunctionalization of metallic implants by calcium phosphate coatings. Bioact Mater. 2019; 4:196-206. PMC: 6529680. DOI: 10.1016/j.bioactmat.2019.05.001. View

Foulke B, Kendal A, Murray D, Pandit H . Fracture healing in the elderly: A review. Maturitas. 2016; 92:49-55. DOI: 10.1016/j.maturitas.2016.07.014. View

Hu D, Ferro F, Yang F, Taylor A, Chang W, Miclau T . Cartilage to bone transformation during fracture healing is coordinated by the invading vasculature and induction of the core pluripotency genes. Development. 2017; 144(2):221-234. PMC: 5394763. DOI: 10.1242/dev.130807. View

Day T, Guo X, Garrett-Beal L, Yang Y . Wnt/beta-catenin signaling in mesenchymal progenitors controls osteoblast and chondrocyte differentiation during vertebrate skeletogenesis. Dev Cell. 2005; 8(5):739-50. DOI: 10.1016/j.devcel.2005.03.016. View

Ding Y, Li R, Nakai M, Majumdar T, Zhang D, Niinomi M . Osteoanabolic Implant Materials for Orthopedic Treatment. Adv Healthc Mater. 2016; 5(14):1740-52. DOI: 10.1002/adhm.201600074. View

Johnell O, Kanis J . Epidemiology of osteoporotic fractures. Osteoporos Int. 2004; 16 Suppl 2:S3-7. DOI: 10.1007/s00198-004-1702-6. View

Duan P, Bonewald L . The role of the wnt/β-catenin signaling pathway in formation and maintenance of bone and teeth. Int J Biochem Cell Biol. 2016; 77(Pt A):23-29. PMC: 4958569. DOI: 10.1016/j.biocel.2016.05.015. View

Fuentes S, Alvina R, Zegarra K, Perez B, Pozo P . Antibacterial Activities of Copper Nanoparticles in Hybrid Microspheres. J Nanosci Nanotechnol. 2019; 19(8):4512-4519. DOI: 10.1166/jnn.2019.16349. View

10.

Hill T, Spater D, Taketo M, Birchmeier W, Hartmann C . Canonical Wnt/beta-catenin signaling prevents osteoblasts from differentiating into chondrocytes. Dev Cell. 2005; 8(5):727-38. DOI: 10.1016/j.devcel.2005.02.013. View

11.

Bibr B, Deyl Z, Lener J, Kucera J, Simkova M . The mechanism of action of molybdenum and tungsten upon collagen structures in vivo. Physiol Bohemoslov. 1987; 36(5):417-24. View

12.

Nikolaou V, Efstathopoulos N, Kontakis G, Kanakaris N, Giannoudis P . The influence of osteoporosis in femoral fracture healing time. Injury. 2009; 40(6):663-8. DOI: 10.1016/j.injury.2008.10.035. View

13.

Barcelo-Oliver M, Garcia-Raso A, Terron A, Molins E, Prieto M, Moreno V . Synthesis and mass spectroscopy kinetics of a novel ternary copper(II) complex with cytotoxic activity against cancer cells. J Inorg Biochem. 2007; 101(4):649-59. DOI: 10.1016/j.jinorgbio.2006.12.008. View

14.

Sha M, Guo Z, Fu J, Li J, Yuan C, Shi L . The effects of nail rigidity on fracture healing in rats with osteoporosis. Acta Orthop. 2009; 80(1):135-8. PMC: 2823242. DOI: 10.1080/17453670902807490. View

15.

Bartsch I, Willbold E, Yarmolenko S, Witte F . In vivo fluorescence imaging of apoptosis during foreign body response. Biomaterials. 2012; 33(29):6926-32. DOI: 10.1016/j.biomaterials.2012.06.039. View

16.

Bliuc D, Nguyen N, Milch V, Nguyen T, Eisman J, Center J . Mortality risk associated with low-trauma osteoporotic fracture and subsequent fracture in men and women. JAMA. 2009; 301(5):513-21. DOI: 10.1001/jama.2009.50. View

17.

Zhai Q, Ji H, Zheng Z, Yu X, Sun L, Liu X . Copper induces apoptosis in BA/F3beta cells: Bax, reactive oxygen species, and NFkappaB are involved. J Cell Physiol. 2000; 184(2):161-70. DOI: 10.1002/1097-4652(200008)184:2<161::AID-JCP3>3.0.CO;2-N. View

18.

Chow D, Leung K, Qin L, Leung A, Cheung W . Low-magnitude high-frequency vibration (LMHFV) enhances bone remodeling in osteoporotic rat femoral fracture healing. J Orthop Res. 2011; 29(5):746-52. DOI: 10.1002/jor.21303. View

19.

Wu W, Xiao Z, Chen Y, Deng Y, Zeng D, Liu Y . CD39 Produced from Human GMSCs Regulates the Balance of Osteoclasts and Osteoblasts through the Wnt/β-Catenin Pathway in Osteoporosis. Mol Ther. 2020; 28(6):1518-1532. PMC: 7264439. DOI: 10.1016/j.ymthe.2020.04.003. View

20.

Maupin K, Droscha C, Williams B . A Comprehensive Overview of Skeletal Phenotypes Associated with Alterations in Wnt/β-catenin Signaling in Humans and Mice. Bone Res. 2015; 1(1):27-71. PMC: 4472092. DOI: 10.4248/BR201301004. View