Biodegradable Zn-0.8Mg-0.2Sr alloy as an internal fixation material exhibits controlled degradation with enhanced osteogenesis
Status PubMed-not-MEDLINE Jazyk angličtina Země Velká Británie, Anglie Médium electronic-ecollection
Typ dokumentu časopisecké články
PubMed
40860423
PubMed Central
PMC12376982
DOI
10.1039/d5ra02009c
PII: d5ra02009c
Knihovny.cz E-zdroje
- Publikační typ
- časopisecké články MeSH
Zinc (Zn) and its alloys are promising candidates for biodegradable metals in medical applications. However, their clinical use in internal fixation is hindered by low mechanical strength, uncontrolled corrosion, and insufficient bioactivity. To address these issues, we developed an extruded Zn-0.8Mg-0.2Sr ternary alloy and systematically evaluated its biological performance. In vitro corrosion tests indicated that Zn-0.8Mg-0.2Sr exhibited superior corrosion resistance, attributed to a dense passivation layer that provided effective protection, controlled degradation kinetics, and milder Zn2+ release. The cytotoxicity of Zn-0.8Mg-0.2Sr toward pre-osteoblasts was concentration-dependent. Within the non-cytotoxic concentration range (Zn2+ ≤8.98 μg mL-1), Zn-0.8Mg-0.2Sr promoted osteogenic differentiation more effectively than pure Zn. Further in vivo studies confirmed favorable biocompatibility and more uniform degradation of Zn-0.8Mg-0.2Sr, with reduced pitting corrosion and structural collapse. Notably, Zn-0.8Mg-0.2Sr exhibited superior performance in promoting bone regeneration and anti-inflammatory immunomodulation compared to pure Zn. These findings highlight Zn-0.8Mg-0.2Sr as a promising alternative to conventional internal fixation materials, offering favorable biocompatibility, controlled biodegradability, and enhanced osteogenesis.
Zobrazit více v PubMed
Chen Q. Thouas G. A. Metallic implant biomaterials. Mater. Sci. Eng., R. 2015;87:1–57.
Kong L. Heydari Z. Lami G. H. Saberi A. Baltatu M. S. Vizureanu P. A comprehensive review of the current research status of biodegradable zinc alloys and composites for biomedical applications. Materials. 2023;16:4797. PubMed PMC
Wang P. Gong Y. Zhou G. Ren W. Wang X. Biodegradable implants for internal fixation of fractures and accelerated bone regeneration. ACS Omega. 2023;8:27920–27931. PubMed PMC
Li D. Zhang D. Yuan Q. Liu L. Li H. Xiong L. Guo X. Yan Y. Yu K. Dai Y. Xiao T. Li Y. Wen C. In vitro and in vivo assessment of the effect of biodegradable magnesium alloys on osteogenesis. Acta Biomater. 2022;141:454–465. PubMed
Liu Y. Zheng Y. Chen X.-H. Yang J.-A. Pan H. Chen D. Wang L. Zhang J. Zhu D. Wu S. Yeung K. W. K. Zeng R.-C. Han Y. Guan S. Fundamental theory of biodegradable metals—definition, criteria, and design. Adv. Funct. Mater. 2019;29:1805402.
Wang N. Ma Y. Shi H. Song Y. Guo S. Yang S. Mg-, Zn-, and Fe-based alloys with antibacterial properties as orthopedic implant materials. Front. Bioeng. Biotechnol. 2022;10:888084. PubMed PMC
Zhang J. Jiang Y. Shang Z. Zhao B. Jiao M. Liu W. Cheng M. Zhai B. Guo Y. Liu B. Shi X. Ma B. Biodegradable metals for bone defect repair: a systematic review and meta-analysis based on animal studies. Bioact. Mater. 2021;6:4027–4052. PubMed PMC
Li H. Hao J. Liu X. Research progress and perspective of metallic implant biomaterials for craniomaxillofacial surgeries. Biomater. Sci. 2024;12:252–269. PubMed
Venezuela J. J. D. Johnston S. Dargusch M. S. The prospects for biodegradable zinc in wound closure applications. Adv. Healthcare Mater. 2019;8:1900408. PubMed
Vojtěch D. Kubásek J. Šerák J. Novák P. Mechanical and corrosion properties of newly developed biodegradable Zn-based alloys for bone fixation. Acta Biomater. 2011;7:3515–3522. PubMed
Mostaed E. Sikora-Jasinska M. Drelich J. W. Vedani M. Zinc-based alloys for degradable vascular stent applications. Acta Biomater. 2018;71:1–23. PubMed PMC
Zheng Y. F. Gu X. N. Witte F. Biodegradable metals. Mater. Sci. Eng., R. 2014;77:1–34.
Cheng J. Liu B. Wu Y. H. Zheng Y. F. Comparative in vitro study on pure metals (Fe, Mn, Mg, Zn and W) as biodegradable metals. J. Mater. Sci. Technol. 2013;29:619–627.
Bowen P. K. Drelich J. Goldman J. Zinc exhibits ideal physiological corrosion behavior for bioabsorbable stents. Adv. Mater. 2013;25:2577–2582. PubMed
Hernández-Escobar D. Champagne S. Yilmazer H. Dikici B. Boehlert C. J. Hermawan H. Current status and perspectives of zinc-based absorbable alloys for biomedical applications. Acta Biomater. 2019;97:1–22. PubMed
Guo H. Xia D. Zheng Y. Zhu Y. Liu Y. Zhou Y. A pure zinc membrane with degradability and osteogenesis promotion for guided bone regeneration: in vitro and in vivo studies. Acta Biomater. 2020;106:396–409. PubMed
Bowen P. K. Shearier E. R. Zhao S. Guillory II R. J. Zhao F. Goldman J. Drelich J. W. Biodegradable metals for cardiovascular stents: from clinical concerns to recent Zn-alloys. Adv. Healthcare Mater. 2016;5:1121–1140. PubMed PMC
Li P. Zhang W. Dai J. Xepapadeas A. B. Schweizer E. Alexander D. Scheideler L. Zhou C. Zhang H. Wan G. Geis-Gerstorfer J. Investigation of zinc–copper alloys as potential materials for craniomaxillofacial osteosynthesis implants. Mater. Sci. Eng., C. 2019;103:109826. PubMed
Jia B. Yang H. Zhang Z. Qu X. Jia X. Wu Q. Han Y. Zheng Y. Dai K. Biodegradable Zn–Sr alloy for bone regeneration in rat femoral condyle defect model: in vitro and in vivo studies. Bioact. Mater. 2021;6:1588–1604. PubMed PMC
Assaf F. H. Abd El-Rehiem S. S. Zaky A. M. Pitting corrosion of zinc in neutral halide solutions. Mater. Chem. Phys. 1999;58:58–63.
Jiang P. Blawert C. Zheludkevich M. L. The corrosion performance and mechanical properties of Mg-Zn based alloys—a review. Corros. Mater. Degrad. 2020;1:92–158.
Zhang X. G., Corrosion and Electrochemistry of Zinc, Springer US, Boston, MA, 1996
Hung C.-C. Chaya A. Liu K. Verdelis K. Sfeir C. The role of magnesium ions in bone regeneration involves the canonical Wnt signaling pathway. Acta Biomater. 2019;98:246–255. PubMed
Zhang Y. Xu J. Ruan Y. C. Yu M. K. O'Laughlin M. Wise H. Chen D. Tian L. Shi D. Wang J. Chen S. Feng J. Q. Chow D. H. K. Xie X. Zheng L. Huang L. Huang S. Leung K. Lu N. Zhao L. Li H. Zhao D. Guo X. Chan K. Witte F. Chan H. C. Zheng Y. Qin L. Implant-derived magnesium induces local neuronal production of CGRP to improve bone-fracture healing in rats. Nat. Med. 2016;22:1160–1169. PubMed PMC
Liu X. Huang H. Zhang J. Sun T. Zhang W. Li Z. Recent advance of strontium functionalized in biomaterials for bone regeneration. Bioengineering. 2023;10:414. PubMed PMC
Yang F. Yang D. Tu J. Zheng Q. Cai L. Wang L. Strontium enhances osteogenic differentiation of mesenchymal stem cells and in vivo bone formation by activating WNT/catenin signaling. Stem Cells. 2011;29:981–991. PubMed
Andersen O. Z. Offermanns V. Sillassen M. Almtoft K. P. Andersen I. H. Sørensen S. Jeppesen C. S. Kraft D. C. E. Bøttiger J. Rasse M. Kloss F. Foss M. Accelerated bone ingrowth by local delivery of strontium from surface functionalized titanium implants. Biomaterials. 2013;34:5883–5890. PubMed
Marx D. Rahimnejad Yazdi A. Papini M. Towler M. A review of the latest insights into the mechanism of action of strontium in bone. Bone Rep. 2020;12:100273. PubMed PMC
Čapek J. Kubásek J. Pinc J. Fojt J. Krajewski S. Rupp F. Li P. Microstructural, mechanical, in vitro corrosion and biological characterization of an extruded Zn-0.8Mg-0.2Sr (wt%) as an absorbable material. Mater. Sci. Eng., C. 2021;122:111924. PubMed
Klíma K. Ulmann D. Bartoš M. Španko M. Dušková J. Vrbová R. Pinc J. Kubásek J. Ulmannová T. Foltán R. Brizman E. Drahoš M. Beňo M. Čapek J. Zn-0.8Mg-0.2Sr (wt.%) absorbable screws—an in vivo biocompatibility and degradation pilot study on a rabbit model. Materials. 2021;14:3271. PubMed PMC
Klíma K. Ulmann D. Bartoš M. Španko M. Dušková J. Vrbová R. Pinc J. Kubásek J. Vlk M. Ulmannová T. Foltán R. Brizman E. Drahoš M. Beňo M. Machoň V. Čapek J. A complex evaluation of the in vivo biocompatibility and degradation of an extruded ZnMgSr absorbable alloy implanted into rabbit bones for 360 days. Int. J. Mol. Sci. 2021;22:13444. PubMed PMC
Li P. Zhang W. Spintzyk S. Schweizer E. Krajewski S. Alexander D. Dai J. Xu S. Wan G. Rupp F. Impact of sterilization treatments on biodegradability and cytocompatibility of zinc-based implant materials. Mater. Sci. Eng., C. 2021;130:112430. PubMed
ISO 10993-16, Biological Evaluation of Medical Devices — Part 16: Toxicokinetic Study Design for Degradation Products and Leachables, International Organization for Standardization, Geneva, Switzerland, 2017
ASTM G3-14, Standard Practice for Conventions Applicable to Electrochemical Measurements in Corrosion Testing, ASTM International, West Conshohocken, PA, United States, 2024
ASTM G59-23, Standard Test Method for Conducting Potentiodynamic Polarization Resistance Measurements, ASTM International, West Conshohocken, PA, United States, 2023
ASTM G96-90, Standard Guide for Online Monitoring of Corrosion in Plant Equipment (Electrical and Electrochemical Methods), ASTM International, West Conshohocken, PA, United States, 2018
ISO 10993-12, Biological Evaluation of Medical Devices —Part 12: Sample Preparation and Reference Materials, International Organization for Standardization, Geneva, Switzerland, 2021
ISO 10993-5, Biological Evaluation of Medical Devices — Part 5: Tests for
Lee N.-H. Kang M. S. Kim T.-H. Yoon D. S. Mandakhbayar N. Jo S. B. Kim H. S. Knowles J. C. Lee J.-H. Kim H.-W. Dual actions of osteoclastic-inhibition and osteogenic-stimulation through strontium-releasing bioactive nanoscale cement imply biomaterial-enabled osteoporosis therapy. Biomaterials. 2021;276:121025. PubMed
Karazisis D. Rasmusson L. Petronis S. Palmquist A. Shah F. A. Agheli H. Emanuelsson L. Johansson A. Omar O. Thomsen P. The effects of controlled nanotopography, machined topography and their combination on molecular activities, bone formation and biomechanical stability during osseointegration. Acta Biomater. 2021;136:279–290. PubMed
Sakai T. Belyakov A. Kaibyshev R. Miura H. Jonas J. J. Dynamic and post-dynamic recrystallization under hot, cold and severe plastic deformation conditions. Prog. Mater. Sci. 2014;60:130–207.
Pinc J. Školáková A. Hybášek V. Msallamová Š. Veřtát P. Ashcheulov P. Vondráček M. Duchoň J. McCarroll I. Hývl M. Banerjee S. Drahokoupil J. Kubásek J. Vojtěch D. Čapek J. A detailed mechanism of degradation behaviour of biodegradable as-ECAPed Zn-0.8Mg-0.2Sr with emphasis on localized corrosion attack. Bioact. Mater. 2023;27:447–460. PubMed PMC
Okamoto H. Sr-Zn (strontium–zinc) J. Phase Equilib. Diffus. 2008;29:127.
Okamoto H. Comment on Mg–Zn (magnesium-zinc) J. Phase Equilib. 1994;15:129–130.
Mayama T. Noda M. Chiba R. Kuroda M. Crystal plasticity analysis of texture development in magnesium alloy during extrusion. Int. J. Plast. 2011;27:1916–1935.
Li R. Ding Y. Zhang H. Wang X. Gao Y. Xu J. Toward high strength and large strain hardening Zn alloys via a novel multiscale-heterostructure strategy. Mater. Sci. Eng., A. 2024;899:146410.
Liu S. Kent D. Doan N. Dargusch M. Wang G. Effects of deformation twinning on the mechanical properties of biodegradable Zn–Mg alloys. Bioact. Mater. 2019;4:8–16. PubMed PMC
Yang Q. Yang J. Liu X. Zhang Y. Li Y. Ao D. Zhong P. Yong K. Crosstalk between the mitochondrial dynamics and oxidative stress in zinc-induced cytotoxicity. Biol. Trace Elem. Res. 2023;201:4419–4428. PubMed
Shearier E. R. Bowen P. K. He W. Drelich A. Drelich J. Goldman J. Zhao F. In vitro cytotoxicity, adhesion, and proliferation of human vascular cells exposed to zinc. ACS Biomater. Sci. Eng. 2016;2:634–642. PubMed PMC
Ma J. Zhao N. Zhu D. Bioabsorbable zinc ion induced biphasic cellular responses in vascular smooth muscle cells. Sci. Rep. 2016;6:26661. PubMed PMC
Tong X. Han Y. Zhou R. Zeng J. Wang C. Yuan Y. Zhu L. Huang S. Ma J. Li Y. Wen C. Lin J. Mechanical properties, corrosion and degradation behaviors, and in vitro cytocompatibility of a biodegradable Zn–5La alloy for bone-implant applications. Acta Biomater. 2023;169:641–660. PubMed
Ma J. Zhao N. Zhu D. Endothelial cellular responses to biodegradable metal zinc. ACS Biomater. Sci. Eng. 2015;1:1174–1182. PubMed PMC
Liu Q. Li A. Liu S. Fu Q. Xu Y. Dai J. Li P. Xu S. Cytotoxicity of biodegradable zinc and its alloys: a systematic review. J. Funct. Biomater. 2023;14:206. PubMed PMC
Qin Y. Liu A. Guo H. Shen Y. Wen P. Lin H. Xia D. Voshage M. Tian Y. Zheng Y. Additive manufacturing of Zn-Mg alloy porous scaffolds with enhanced osseointegration: in vitro and in vivo studies. Acta Biomater. 2022;145:403–415. PubMed
Li P. Zhou N. Qiu H. Maitz M. F. Wang J. Huang N. In vitro and in vivo cytocompatibility evaluation of biodegradable magnesium-based stents: a review. Sci. China Mater. 2018;61:501–515.
Hybasek V. Kubasek J. Capek J. Alferi D. Pinc J. Jiru J. Fojt J. Influence of model environment complexity on corrosion mechanism of biodegradable zinc alloys. Corros. Sci. 2021;187:109520.
Su Y. Yang H. Gao J. Qin Y. Zheng Y. Zhu D. Interfacial zinc phosphate is the key to controlling biocompatibility of metallic zinc implants. Adv. Sci. 2019;6:1900112. PubMed PMC
Su Y. Wang K. Gao J. Yang Y. Qin Y.-X. Zheng Y. Zhu D. Enhanced cytocompatibility and antibacterial property of zinc phosphate coating on biodegradable zinc materials. Acta Biomater. 2019;98:174–185. PubMed PMC
Li Y. Zhang H. Lu Y. Yang X. Wang G. Wang Y. Tang K. Huang S. Xiao G. Construction of magnesium phosphate chemical conversion coatings with different microstructures on titanium to enhance osteogenesis and angiogenesis. ACS Appl. Mater. Interfaces. 2024;16:21672–21688. PubMed
Li P. Dai J. Li Y. Alexander D. Čapek J. Geis-Gerstorfer J. Wan G. Han J. Yu Z. Li A. Zinc based biodegradable metals for bone repair and regeneration: bioactivity and molecular mechanisms. Mater. Today Bio. 2024;25:100932. PubMed PMC
Xu J. Bao G. Jia B. Wang M. Wen P. Kan T. Zhang S. Liu A. Tang H. Yang H. Yue B. Dai K. Zheng Y. Qu X. An adaptive biodegradable zinc alloy with bidirectional regulation of bone homeostasis for treating fractures and aged bone defects. Bioact. Mater. 2024;38:207–224. PubMed PMC
Roy M. Fielding G. Bandyopadhyay A. Bose S. Effects of zinc and strontium substitution in tricalcium phosphate on osteoclast differentiation and resorption. Biomater. Sci. 2013;1:74–82. PubMed PMC
Cheng X. Tian W. Yang J. Wang J. Zhang Y. Engineering approaches to manipulate osteoclast behavior for bone regeneration. Mater. Today Bio. 2024;26:101043. PubMed PMC
Daponte V. Henke K. Drissi H. Current perspectives on the multiple roles of osteoclasts: mechanisms of osteoclast-osteoblast communication and potential clinical implications. eLife. 2024;13:e95083. PubMed PMC
Veis D. J. O'Brien C. A. Osteoclasts, master sculptors of bone. Annu. Rev. Pathol.: Mech. Dis. 2023;18:257–281. PubMed
Niu Y. Wang Z. Shi Y. Dong L. Wang C. Modulating macrophage activities to promote endogenous bone regeneration: biological mechanisms and engineering approaches. Bioact. Mater. 2020;6:244–261. PubMed PMC
Wang T. Bai J. Lu M. Huang C. Geng D. Chen G. Wang L. Qi J. Cui W. Deng L. Engineering immunomodulatory and osteoinductive implant surfaces via mussel adhesion-mediated ion coordination and molecular clicking. Nat. Commun. 2022;13:160. PubMed PMC
Alvarez M. M. Liu J. C. Santiago G. T. Cha B.-H. Vishwakarma A. Ghaemmaghami A. Khademhosseini A. Delivery strategies to control inflammatory response: modulating M1-M2 polarization in tissue engineering applications. J. Controlled Release. 2016;240:349–363. PubMed PMC
Zhu F. Wang S. Zhu X. Pang C. Cui P. Yang F. Li R. Zhan Q. Xin H. Potential effects of biomaterials on macrophage function and their signalling pathways. Biomater. Sci. 2023;11:6977–7002. PubMed
Hu Z. Ma C. Rong X. Zou S. Liu X. Immunomodulatory ECM-like microspheres for accelerated bone regeneration in diabetes mellitus. ACS Appl. Mater. Interfaces. 2018;10:2377–2390. PubMed PMC
Zhu Y. Liang H. Liu X. Wu J. Yang C. Wong T. M. Kwan K. Y. H. Cheung K. M. C. Wu S. Yeung K. W. K. Regulation of macrophage polarization through surface topography design to facilitate implant-to-bone osteointegration. Sci. Adv. 2021;7:eabf6654. PubMed PMC
Luo M. Zhao F. Liu L. Yang Z. Tian T. Chen X. Cao X. Chen D. Chen X. IFN-γ/SrBG composite scaffolds promote osteogenesis by sequential regulation of macrophages from M1 to M2. J. Mater. Chem. B. 2021;9:1867–1876. PubMed
Li N. Cao Y. Liu J. Zou W. Chen M. Cao H. Deng S. Liang J. Yuan T. Wang Q. Fan Y. Zhang X. Microenvironment-responsive release of Mg2+ from tannic acid decorated and multilevel crosslinked hydrogels accelerates infected wound healing. J. Mater. Chem. B. 2024;12:6856–6873. PubMed
Miao Q. Yang X. Diao J. Ding H. Wu Y. Ren X. Gao J. Ma M. Yang S. 3D printed strontium-doped calcium phosphate ceramic scaffold enhances early angiogenesis and promotes bone repair through the regulation of macrophage polarization. Mater. Today Bio. 2023;23:100871. PubMed PMC
Ben Amara H. Martinez D. C. Iskhakova K. Emanuelsson L. Norlindh B. Johansson Loo A. Wieland D. C. F. Zeller-Plumhoff B. Willumeit-Römer R. Plocinski T. Swieszkowski W. Shah F. A. Palmquist A. Omar O. Thomsen P. Multifaceted bone response to immunomodulatory magnesium implants: osteopromotion at the interface and adipogenesis in the bone marrow. Biomaterials. 2025;314:122779. PubMed