AccScience Publishing / IJB / Volume 9 / Issue 5 / DOI: 10.18063/ijb.769
Cite this article
97
Download
973
Views
Journal Browser
Volume | Year
Issue
Search
News and Announcements
View All
RESEARCH ARTICLE

3D-printed biodegradable magnesium alloy scaffolds with zoledronic acid-loaded ceramic composite coating promote osteoporotic bone defect repair

Zhaoyang Ran1,2† Yan Wang3† Jiaxin Li4† Wenyu Xu5 Jia Tan1,2 Bojun Cao1,2 Dinghao Luo1,2 Yiwen Ding5 Junxiang Wu1,2 Lei Wang1,2 Kai Xie1,2 Liang Deng1,2 Penghuai Fu5* Xiaoying Sun3* Liyi Shi3 Yongqiang Hao1,2*
Show Less
1 Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China
2 Shanghai Engineering Research Center of Innovative Orthopaedic Instruments and Personalized Medicine, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China
3 Nano-Science & Technology Center, College of Sciences, Shanghai University, Shanghai 200444, China
4 Department of Orthopedics, The Second Affiliated Hospital of Harbin Medical University, Harbin 150001, China
5 National Engineering Research Center of Light Alloy Net Forming & State Key Laboratory of Metal Matrix Composite, Shanghai Jiao Tong University, Shanghai 200240, China
Submitted: 19 March 2023 | Accepted: 27 April 2023 | Published: 7 June 2023
© 2023 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
Abstract

Osteoporotic fracture is one of the most serious complications of osteoporosis. Most fracture sites have bone defects, and restoring the balance between local osteogenesis and bone destruction is difficult during the repair of osteoporotic bone defects. In this study, we successfully fabricated three-dimensional (3D)-printed biodegradable magnesium alloy (Mg-Nd-Zn-Zr) scaffolds and prepared a zoledronic acid-loaded ceramic composite coating on the surface of the scaffolds. The osteogenic effect of Mg and the osteoclast inhibition effect of zoledronic acid were combined to promote osteoporotic bone defect repair. In vitro degradation and drug release experiments showed that the coating significantly reduced the degradation rate of 3D-printed Mg alloy scaffolds and achieved a slow release of loaded drugs. The degradation products of drug-loaded coating scaffolds can promote osteogenic differentiation of bone marrow mesenchymal stem cells as well as inhibit the formation of osteoclasts and the bone resorption by regulating the expression of related genes. Compared with the uncoated scaffolds, the drug-coated scaffolds degraded at a slower rate, and more new bone grew into these scaffolds. The healing rate and quality of the osteoporotic bone defects significantly improved in the drug-coated scaffold group. This study provides a new method for theoretical research and clinical treatment using functional materials for repairing osteoporotic bone defects.

Keywords
Osteoporotic fractures
Magnesium alloys
3D printing
Bone defects repair
Surface modification
References

Johnell O, Kanis JA, 2006, An estimate of the worldwide prevalence and disability associated with osteoporotic fractures. Osteoporos Int, 17(12): 1726–1733. https://doi.org/10.1007/s00198-006-0172-4

Reid IR, 2020, A broader strategy for osteoporosis interventions. Nat Rev Endocrinol, 16(6): 333–339. https://doi.org/10.1038/s41574-020-0339-7

Myeroff C, Archdeacon M, 2011, Autogenous bone graft: Donor sites and techniques. J Bone Joint Surg Am, 93(23): 2227–2236. https://doi.org/10.2106/JBJS.J.01513

Sukotjo C, Lima-Neto TJ, Santiago Junior JF, et al., 2020, Is there a role for absorbable metals in surgery? A systematic review and meta-analysis of Mg/Mg alloy based implants. Materials (Basel), 13(18): 3914. https://doi.org/10.3390/ma13183914

John AA, Xie J, Yang YS, et al., 2022, AAV-mediated delivery of osteoblast/osteoclast-regulating miRNAs for osteoporosis therapy. Mol Ther Nucleic Acids, 29: 296–311. https://doi.org/10.1016/j.omtn.2022.07.008

Kraus T, Fischerauer SF, Hanzi AC, et al., 2012, Magnesium alloys for temporary implants in osteosynthesis: In vivo studies of their degradation and interaction with bone. Acta Biomater, 8(3): 1230–1238. https://doi.org/10.1016/j.actbio.2011.11.008

Min S, Wang C, Liu B, et al., 2023, The biological properties of 3D-printed degradable magnesium alloy WE43 porous scaffolds via the oxidative heat strategy. Int J Bioprint, 9(3): 94–104. https://doi.org/10.18063/ijb.686

Chaya A, Yoshizawa S, Verdelis K, et al., 2015, In vivo study of magnesium plate and screw degradation and bone fracture healing. Acta Biomater, 18: 262–269. https://doi.org/10.1016/j.actbio.2015.02.010

 

Li Y, Zhou J, Pavanram P, et al., 2018, Additively manufactured biodegradable porous magnesium. Acta Biomater, 67: 378–392. https://doi.org/10.1016/j.actbio.2017.12.008

Dong J, Li Y, Lin P, et al., 2020, Solvent-cast 3D printing of magnesium scaffolds. Acta Biomater, 114: 497–514. https://doi.org/10.1016/j.actbio.2020.08.002

Al-Ketan O, Rowshan R, Abu Al-Rub RK, 2018, Topology-mechanical property relationship of 3D printed strut, skeletal, and sheet based periodic metallic cellular materials. Addit Manuf, 19: 167–183. https://doi.org/10.1016/j.addma.2017.12.006

Zhang XY, Fang G, Zhou J, 2017, Additively manufactured scaffolds for bone tissue engineering and the prediction of their mechanical behavior: A review. Materials, 10(1): 50. https://doi.org/10.3390/ma10010050

Xie K, Wang NQ, Guo Y, et al., 2022, Additively manufactured biodegradable porous magnesium implants for elimination of implant-related infections: An in vitro and in vivo study. Bioact Mater, 8: 140–152. https://doi.org/10.1016/j.bioactmat.2021.06.032

Rossi S, Deflorian F, Fedel M, 2019, Polysilazane-based coatings: Corrosion protection and anti-graffiti properties(dagger). Surf Eng, 35(4): 343–350. https://doi.org/10.1080/02670844.2018.1465748

Reid IR, Billington EO, 2022, Drug therapy for osteoporosis in older adults. Lancet, 399(10329): 1080–1092. https://doi.org/10.1016/S0140-6736(21)02646-5

Johnston CB, Dagar M, 2020, Osteoporosis in older adults. Med Clin North Am, 104(5): 873–884. https://doi.org/10.1016/j.mcna.2020.06.004

 

Black DM, Delmas PD, Eastell R, et al., 2007, Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med, 356(18): 1809–1822. https://doi.org/10.1056/NEJMoa067312

Li GY, Zhang L, Wang L, et al., 2018, Dual modulation of bone formation and resorption with zoledronic acid-loaded biodegradable magnesium alloy implants improves osteoporotic fracture healing: An in vitro and in vivo study. Acta Biomater, 65: 486–500. https://doi.org/10.1016/j.actbio.2017.10.033

Liu A, Lin D, Zhao H, et al., 2021, Optimized BMSC-derived osteoinductive exosomes immobilized in hierarchical scaffold via lyophilization for bone repair through Bmpr2/ Acvr2b competitive receptor-activated Smad pathway. Biomaterials, 272: 120718. https://doi.org/10.1016/j.biomaterials.2021.120718

Yuan K, Mei J, Shao D, et al., 2020, Cerium oxide nanoparticles regulate osteoclast differentiation bidirectionally by modulating the cellular production of reactive oxygen species. Int J Nanomed, 15: 6355–6372. https://doi.org/10.2147/IJN.S257741

Chen QX, Li JY, Han F, et al., 2022, A multifunctional composite hydrogel that rescues the ROS microenvironment and guides the immune response for repair of osteoporotic bone defects. Adv Func Mater, 32(27): 2201067. https://doi.org/10.1002/adfm.202201067

Niu J, Yuan G, Liao Y, et al., 2013, Enhanced biocorrosion resistance and biocompatibility of degradable Mg-Nd-Zn- Zr alloy by brushite coating. Mater Sci Eng C Mater Biol Appl, 33(8): 4833–4841. https://doi.org/10.1016/j.msec.2013.08.008

Lin ZJ, Wu J, Qiao W, et al., 2018, Precisely controlled delivery of magnesium ions thru sponge-like monodisperse PLGA/nano-MgO-alginate core-shell microsphere device to enable in-situ bone regeneration. Biomaterials, 174: 1–16. https://doi.org/10.1016/j.biomaterials.2018.05.011

Zhai Z, Qu X, Li H, et al., 2014, The effect of metallic magnesium degradation products on osteoclast-induced osteolysis and attenuation of NF-kappaB and NFATc1 signaling. Biomaterials, 35(24): 6299–6310. https://doi.org/10.1016/j.biomaterials.2014.04.044

Wong HM, Wu SL, Chu PK, et al., 2013, Low-modulus Mg/PCL hybrid bone substitute for osteoporotic fracture fixation. Biomaterials, 34(29): 7016–7032. https://doi.org/10.1016/j.biomaterials.2013.05.062

Lin SH, Yang GZ, Jiang F, et al., 2019, A magnesium-enriched 3D culture system that mimics the bone development microenvironment for vascularized bone regeneration. Adv Sci, 6(12): 1900209. https://doi.org/10.1002/advs.201900209

Cipriano AF, Lin JJ, Lin A, et al., 2017, Degradation of bioresorbable Mg-4Zn-1Sr intramedullary pins and associated biological responses in vitro and in vivo. ACS Appl Mater Interfaces, 9(51): 44332–44355. https://doi.org/10.1021/acsami.7b15975

Zhang YL, Shi LT, Tang PF, et al., 2017, Comparison of the efficacy between two micro-operative therapies of old patients with osteoporotic vertebral compression fracture: A network meta-analysis. J Cell Biochem, 118(10): 3205–3212. https://doi.org/10.1002/jcb.25966

Reid DM, Devogelaer JP, Saag K, et al., 2009, Zoledronic acid and risedronate in the prevention and treatment of glucocorticoid-induced osteoporosis (HORIZON): A multicentre, double-blind, double-dummy, randomised controlled trial. Lancet, 373(9671): 1253–1263. https://doi.org/10.1016/S0140-6736(09)60250-6

Greiner S, Kadow-Romacker A, Schmidmaier G, et al., 2009, Cocultures of osteoblasts and osteoclasts are influenced by local application of zoledronic acid incorporated in a poly(D,L-lactide) implant coating. J Biomed Mater Res A, 91(1): 288–295. https://doi.org/10.1002/jbm.a.32245

Razavi M, Fathi M, Savabi O, et al., 2014, In vivo study of nanostructured diopside (CaMgSi2O6) coating on magnesium alloy as biodegradable orthopedic implants. Appl Surf Sci, 313: 60–66. https://doi.org/10.1016/j.apsusc.2014.05.130

Yang M, Dong Y, He Q, et al., 2020, Hydrogen: A novel option in human disease treatment. Oxid Med Cell Longev, 2020: 8384742. https://doi.org/10.1155/2020/8384742

Ohta S, 2014, Molecular hydrogen as a preventive and therapeutic medical gas: Initiation, development and potential of hydrogen medicine. Pharmacol Therapeut, 144(1): 1–11. https://doi.org/10.1016/j.pharmthera.2014.04.006

Share
Back to top
International Journal of Bioprinting, Electronic ISSN: 2424-8002 Print ISSN: 2424-7723, Published by AccScience Publishing