Keywords
biodegradable fixators
orthopedic and trauma implants
magnesium
magnesium alloys
literature review
How to Cite
Abstract
Background. In recent years, countries such as Japan, China, the United States, and others have been actively searching for bioresorbable materials for osteosynthesis that do not require removal. According to preliminary data, biodegradable osteosynthesis fixators possess osteoinductive and osteoproliferative properties, positively influencing bone healing at the fracture site. Currently, osteosynthesis involves the use of implants made of steel and titanium alloys. The main disadvantage of such fixators is the need for a secondary surgical procedure to remove them, which extends the patient’s disability period.
Objective. This study aims to analyze and summarize scientific research on the effects of metal ions on bone tissue regeneration, vascularization, and surrounding tissues when using biodegradable materials for osteosynthesis of fractures at the current stage.
Materials and Methods. Based on data from the scientometric databases Scopus and Web of Science, a systematic approach, along with bibliosemantic and analytical methods, was applied.
Results and Discussion. Modern tissue engineering is gradually shifting from the use of bioinert materials to the development and implementation of biodegradable materials capable of actively stimulating tissue regeneration. It has been established that metal ions play a key role in the biological processes of the human body. In particular, zinc (Zn), boron (B), and zirconium (Zr) ions have significant potential in stimulating the development and regeneration of bone tissue. They contribute to biochemical reactions involved in bone metabolism, enhance regenerative processes, and positively influence the activity of osteoblasts, osteoclasts, immune system cells, endothelial cells, and fibroblasts. The degradation products of magnesium (Mg)-based implants play an important role in shaping the bone microenvironment, participating in complex interactions between osteoblasts, osteoclasts, endothelial cells, and immune cells. This contributes to effective bone tissue regeneration.
References
Zhou C, Wang C, Xu K, Niu Z, Zou S, Zhang D, et al. Hydrogel platform with tunable stiffness based on magnetic nanoparticles cross-linked GelMA for cartilage regeneration and its intrinsic biomechanism. Bioact Mater. 2022; 30(5):615-628. doi: 10.1016/j.bioactmat.2022.07.013
Богуслаєв ВО, Бєліков СБ, Колесник ЮМ, Цивірко ЕІ, Чорний ВМ, Головаха МЛ, Яцун ЄВ. Сплави на основі магнію для імплантатів при остеосинтезі. Запоріжжя: АТ «МоторСіч». (2020)
Bohuslaiev VO, Bielikov SB, Kolesnyk YuM, Tsyvirko EI, Chornyi VM, Holovakha ML, Yatsun YeV. Splavy na osnovi mahniiu dlia implantativ pry osteosyntezi. Zaporizhzhia: AT «MotorSich». (2020). [in Ukrainian]
Shan Z, Xie X, Wu X, Zhuang S, Zhang C. Development of degradable magnesium-based metal implants and their function in promoting bone metabolism (A review). J Orthop Translat. 2022;(8)36:184-193. doi:10.1016/j.jot.2022.09.013
Wang X., Tang M. Bioceramic materials with ion‐mediated multifunctionality for wound healing. Smart Medicine. 2022;1(1):20220032.https://doi.org/10.1002/SMMD.20220032
Чорний ВМ, Головаха МЛ, Яцун ЄВ. Клінічний приклад використання біорезорбційного малеолярного гвинта для остеосинтезу внутрішньої кісточки. Запорожский медицинский журнал. 2020;1122(5):727–731. https://doi.org/10.14739/2310-1210.2020.5ххххх .
Chornyi VM, Holovakha ML, Yatsun YeV. Clinical example of using a bioresorbable malleolar screw for osteosynthesis of the medial malleolus. Zaporozhye Medical Journal. 2020;1122(5):727–731. [in Ukrainian]
Hang Y, Xu J, Ruan YC, Yu MK, O'Laughlin M, Wise H, et al. Implant-derived magnesium induces local neuronal production of CGRP to improve bone-fracture healing in rats. Nat Med. 2016;22(10):1160-1169. doi: 10.1038/nm.4162
Amukarimi S, Mozafari M. Biodegradable magnesium-based biomaterials: An overview of challenges and opportunities. MedComm. 2021;8(3):123-144. doi: 10.1002/mco2.59
Lu Y, Deshmukh S, Jones I, Chiu YL. Biodegradable magnesium alloys for orthopaedic applications. Biomater Transl. 2021;28(3):214-235. doi: 10.12336/biomatertransl.2021.03.005
Zhu WY, Guo J, Yang WF, Tao ZY, Lan X, Wang L, Xu J, Qin L, Su YX. Biodegradable
magnesium implant enhances angiogenesis and alleviates medication-related osteonecrosis of the
jaw in rats. J Orthop Translat. 2022;33:153-161. doi:10.1016/j.jot.2022.03.004.
Kamrani S, Fleck C. Biodegradable magnesium alloys as temporary orthopaedic implants: a review. Biometals. 2019;32(2):185-193. doi: 10.1007/s10534-019-00170-y
Gonzalez J, Hou RQ, Nidadavolu EPS, Willumeit-Römer R, Feyerabend F. Magnesium degradation under physiological conditions - Best practice. Bioact Mater. 2018;14(2):174-185. doi: 10.1016/j.bioactmat.2018.01.003
Grünewald TA, Rennhofer H, Hesse B, Burghammer M, Stanzl-Tschegg SE, Cotte M, et al. Magnesium from bioresorbable implants: Distribution and impact on the nano- and mineral structure of bone. Biomaterials. 2016;76:250-60. doi: 10.1016/j.biomaterials.2015.10.054
Razzaque MS. Magnesium: Are We Consuming Enough? Nutrients. 2018;10(12):1863. doi: 10.3390/nu10121863
Guo JD, Li L, Shi YM, Wang HD, Hou SX. Hydrogen water consumption prevents osteopenia in ovariectomized rats. Br J Pharmacol. 2013;168(6):1412-20. doi: 10.1111/bph.12036.
Belluci MM, de Molon RS, Rossa CJr, Tetradis S, Giro G, Cerri PS, et al. Severe magnesium deficiency compromises systemic bone mineral density and aggravates inflammatory bone resorption. J Nutr Biochem. 2020;77:108301. doi: 10.1016/j.jnutbio.2019.108301
Zhai Z, Qu X, Li H, Yang K, Wan P, Tan L, et al. The effect of metallic magnesium degradation products on osteoclast-induced osteolysis and attenuation of NF-κB and NFATc1 signaling. Biomaterials. 2014;35(4):299-310. doi: 10.1016/j.biomaterials.2014.04.044
Xie H, Cui Z, Wang L, Xia Z, Hu Y, Xian L, et al. PDGF-BB secreted by preosteoclasts induces angiogenesis during coupling with osteogenesis. Nat Med. 2014;20(11):127-128. doi: 10.1038/nm.3668
Yoshizawa S, Brown A, Barchowsky A, Sfeir C. Magnesium ion stimulation of bone marrow stromal cells enhances osteogenic activity, simulating the effect of magnesium alloy degradation. Acta Biomater. 2014;10(6):283-342. doi: 10.1016/j.actbio.2014.02.002
Chen ZT, Klein T, Murray RZ, Crawford R, Chang J, Wu CT, et al. Osteoimmunomodulation for the development of advanced bone biomaterials. Mater Today. 2016;19(6):304-321. doi: 10.1016/j.mattod.2015.11.004.
Wang M, Yu Y, Dai K, Ma Z, Liu Y, Wang J, et al. Improved osteogenesis and angiogenesis of magnesium-doped calcium phosphate cement via macrophage immunomodulation. Biomater Sci. 2016;4(11):1574-1583. doi: 10.1039/c6bm00290k
Moon S, Hong J, Go S, Kim BS. Immunomodulation for Tissue Repair and Regeneration. Tissue Eng Regen Med. 2023;20(3):389-409. doi: 10.1007/s13770-023-00525-0.
Li B, Cao H, Zhao Y, Cheng M, Qin H, Cheng T, et al. In vitro and in vivo responses of macrophages to magnesium-doped titanium. Sci Rep. 2021;11(1):59-89. doi: 10.1038/s41598-021-88664-z
Ibako P, Nowacki W, Castiglioni S, Mazur A, Maier JA. Extracellular magnesium and calcium blockers modulate macrophage activity. Magnes Res. 2016;29(1):11-21. doi: 10.1684/mrh.2016.0398
Plum LM, Rink L, Haase H. The essential toxin: impact of zinc on human health. Int J Environ Res Public Health. 2010;7(4):42-65. doi: 10.3390/ijerph7041342
Yuan T, Wang H, Wang Y, Dong S, Ge J, Li Z, et al. Inhibition of insulin degrading enzyme suppresses osteoclast hyperactivity via enhancing Nrf2-dependent antioxidant response in glucocorticoid-induced osteonecrosis of the femoral head. Mol Med. 2024;30:111. https://doi.org/10.1186/s10020-024-00880-1
Fung EB, Kwiatkowski JL, Huang JN, Gildengorin G, King JC, Vichinsky EP. Zinc supplementation improves bone density in patients with thalassemia: a double-blind, randomized, placebo-controlled trial. Am J Clin Nutr. 2013;98(4):960-71. doi: 10.3945/ajcn.112.049221.
Li C, Guo C, Fitzpatrick V, Ibrahim A, Zwierstra MJ, Hanna P, et al. Design of biodegradable, implantable devices towards clinical translation. Nat Rev Mater. 2020;5(1):61-81. doi: 10.1038/s41578-019-0150-z.
Bao G, Wang K, Yang L, He J, He B, Xu X, et al. Feasibility evaluation of a Zn-Cu alloy for intrauterine devices: In vitro and in vivo studies. Acta Biomater. 2022;142:374-387. doi: 10.1016/j.actbio.2022.01.053.
Wen X, Wang J, Pei X, Zhang X. Zinc-based biomaterials for bone repair and regeneration: mechanism and applications. J Mater Chem B. 2023;11(48):11405-11425. doi: 10.1039/d3tb01874a
Bosch-Rué È, Díez-Tercero L, Buitrago JO, Castro E, Pérez RA. Angiogenic and immunomodulation role of ions for initial stages of bone tissue regeneration. Acta Biomater. 2023;166:14-41. doi: 10.1016/j.actbio.2023.06.001
Su Y, Cappock M, Dobres S, Kucine AJ, Waltzer WC, Zhu D. Supplemental mineral ions for bone regeneration and osteoporosis treatment. Eng Regen. 2023;4(2):170-182. doi: 10.1016/j.engreg.2023.02.003.
Gao C, Peng S, Feng P, Shuai C. Bone biomaterials and interactions with stem cells. Bone Res. 2017;5:17059. doi: 10.1038/boneres.2017.59
Gao X, Xue Y, Zhu Z, Chen J, Liu Y, Cheng X, et al. Nanoscale Zeolitic Imidazolate Framework-8 Activator of Canonical MAPK Signaling for Bone Repair. ACS Appl Mater Interfaces. 2020;13(1):97-111. doi: 10.1021/acsami.0c15945
Park KH, Choi Y, Yoon DS, Lee KM, Kim D, Lee JW. Zinc Promotes Osteoblast Differentiation in Human Mesenchymal Stem Cells Via Activation of the cAMP-PKA-CREB Signaling Pathway. Stem Cells Dev. 2018;27(16):1125-1135. doi: 10.1089/scd.2018.0023
Wang S, Li R, Xia D, Zhao X, Zhu Y, Gu R, et al. The impact of Zn-doped synthetic polymer materials on bone regeneration: a systematic review. Stem Cell Res Ther. 2021;12(1):123. doi: 10.1186/s13287-021-02195-y
Jamel MM, Jamel MM, Lopez HF. Designing Advanced Biomedical Biodegradable Mg Alloys: A Review. Metals. 2022;12(1):85. https://doi.org/10.3390/met12010085
Sreenivasamurthy SA, Akhter FF, Akhter A, Su Y, Zhu D. Cellular mechanisms of biodegradable zinc and magnesium materials on promoting angiogenesis. Biomater Adv. 2022;139:213023. doi: 10.1016/j.bioadv.2022.213023
Su N, Villicana C, Yang F. Immunomodulatory strategies for bone regeneration: A review from the perspective of disease types. Biomaterials. 2022;28(6):121604. doi: 10.1016/j.biomaterials.2022.121604
Meng G, Wu X, Yao R, He J, Yao W, Wu F. Effect of zinc substitution in hydroxyapatite coating on osteoblast and osteoclast differentiation under osteoblast/osteoclast co-culture. Regen Biomater. 2019;6(6):349-359. doi: 10.1093/rb/rbz001
Zhu L, Hua F, Ding W, Ding K, Zhang Y, Xu C. The correlation between the Th17/Treg cell balance and bone health. Immun Ageing. 2020;(17)30. doi: 10.1186/s12979-020-00202-z
Martin KE, García AJ. Macrophage phenotypes in tissue repair and the foreign body response: Implications for biomaterial-based regenerative medicine strategies. Acta Biomater. 2021;(10)133:4-16. doi: 10.1016/j.actbio.2021.03.038.
Adusei KM, Ngo TB, Sadtler K. T lymphocytes as critical mediators in tissue regeneration, fibrosis, and the foreign body response. Acta Biomater. 2021;(10)133:17-33. doi: 10.1016/j.actbio.2021.04.023
Chen B, You Y, Ma A, Song Y, Jiao J, Song L, et al. Zn-Incorporated TiO2 Nanotube Surface Improves Osteogenesis Ability Through Influencing Immunomodulatory Function of Macrophages. Int J Nanomedicine. 2020;15(5):2095-2118. doi: 10.2147/IJN.S244349
Liu J, Zhao Y, Zhang Y, Yao X, Hang R. Exosomes derived from macrophages upon Zn ion stimulation promote osteoblast and endothelial cell functions. J Mater Chem B. 2021;9(18):3800-3807. doi: 10.1039/d1tb00112d
Nielsen FH, Stoecker BJ. Boron and fish oil have different beneficial effects on strength and trabecular microarchitecture of bone. J Trace Elem Med Biol. 2009;23(3):195-203. doi: 10.1016/j.jtemb.2009.03.003.
Dzondo-Gadet M, Mayap-Nzietchueng R, Hess K, Nabet P, Belleville F, Dousset B. Action of boron at the molecular level: effects on transcription and translation in an acellular system. Biol Trace Elem Res. 2002;85(1):23-33. doi:10.1385/BTER:85:1:23.
Baghdadi I, Zaazou A, Tarboush BA, Zakhour M, Özcan M, Salameh Z. Physiochemical properties of a bioceramic-based root canal sealer reinforced with multi-walled carbon nanotubes, titanium carbide and boron nitride biomaterials. J Mech Behav Biomed Mater. 2020;110:103892. doi:10.1016/j.jmbbm.2020.103892
Gizer M, Köse S, Karaosmanoglu B, Taskiran EZ, Berkkan A, Timuçin M, et al. The Effect of Boron-Containing Nano-Hydroxyapatite on Bone Cells. Biol Trace Elem Res. 2020;193(2):364-376. doi: 10.1007/s12011-019-01710-w.
Boyacioglu O, Orenay-Boyacioglu S, Yildirim H, Korkmaz M. Boron intake, osteocalcin polymorphism and serum level in postmenopausal osteoporosis. J Trace Elem Med Biol. 2018;48:52-56. doi:10.1016/j.jtemb.2018.03.005
Rondanelli M, Faliva MA, Peroni G, Infantino V, Gasparri C, Iannello G, et al. Pivotal role of boron supplementation on bone health: A narrative review. J Trace Elem Med Biol. 2020;62:126577. doi: 10.1016/j.jtemb.2020.126577.
Schünemann FH, Galárraga-Vinueza ME, Magini R, Fredel M, Silva F, Souza JCM, et al. Zirconia surface modifications for implant dentistry. Mater Sci Eng C Mater Biol Appl. 2019;98:1294-1305. doi: 10.1016/j.msec.2019.01.062
Cunha W, Carvalho O, Henriques B, Silva FS, Özcan M, Souza JCM. Surface modification of zirconia dental implants by laser texturing. Lasers Med Sci. 2022;37(1):77-93. doi: 10.1007/s10103-021-03475-y
Han K, Sathiyaseelan A, Lu Y, Kim KM, Wang MH. Agar/carboxymethyl cellulose composite film loaded with hydroxyapatite nanoparticles for bone regeneration. Cellulose. 2024;31:9319–9334. doi:10.1007/s10570-024-06148-5
Yousuke T. Crushing of grain of cast details from magnesian alloys. Chiba kogyo kenkyu = Rept Chiba Inst Technol. 1999;46:349-350.
Huan ZG, Leeflang MA, Zhou J, Fratila-Apachitei LE, Duszczyk J. In vitro degradation
behavior and cytocompatibility of Mg-Zn-Zr alloys. J Mater Sci Mater Med. 2010 Sep;21(9):2623-
doi:10.1007/s10856-010-4111-8.
Gouveia PF, Mesquita-Guimarães J, Galárraga-Vinueza ME, Souza JCM, Silva FS, Fredel MC, et al. In-vitro mechanical and biological evaluation of novel zirconia reinforced bioglass scaffolds for bone repair. J Mech Behav Biomed Mater. 2021;114:104164. doi:10.1016/j.jmbbm.2020.104164
Souza JC, Silva JB, Aladim A, Carvalho O, Nascimento RM, Silva FS, et al. Effect of Zirconia and Alumina Fillers on the Microstructure and Mechanical Strength of Dental Glass Ionomer Cements. Open Dent J. 2016;10:58-68. doi: 10.2174/1874210601610010058
Mesquita-Guimarães J, Detsch R, Souza AC, Henriques B, Silva FS, Boccaccini AR, et al. Cell adhesion evaluation of laser-sintered HAp and 45S5 bioactive glass coatings on micro-textured zirconia surfaces using MC3T3-E1 osteoblast-like cells. Mater Sci Eng C. 2020;109:110492. doi:10.1016/j.msec.2019.110492
Mandelli F, Traini T, Ghensi P. Customized-3D zirconia barriers for guided bone regeneration (GBR): clinical and histological findings from a proof-of-concept case series. J Dent. 2021;114:103780. doi: 10.1016/j.jdent.2021.103780.
Whited BM, Skrtic D, Love BJ, Goldstein AS. Osteoblast response to zirconia-hybridized pyrophosphate-stabilized amorphous calcium phosphate. J Biomed Mater Res A. 2006;76(3):596-604. doi: 10.1002/jbm.a.30573
An SH, Matsumoto T, Miyajima H, Nakahira A, Kim KH, Imazato S. Porous zirconia/hydroxyapatite scaffolds for bone reconstruction. Dent Mater. 2012;12;28:1221-31. doi: 10.1016/j.dental.2012.09.001.
Cunha W, Carvalho O, Henriques B, Silva FS, Özcan M, Souza JCM. Surface modification of zirconia dental implants by laser texturing. Lasers Med Sci. 2022;37(1):77-93. doi: 10.1007/s10103-021-03475-y
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