journal article·2023-12-17Open access

Bone Regeneration Induced by Patient-Adapted Mg Alloy-Based Scaffolds for Bone Defects: Present and Future Perspectives

Veronica Manescu (Paltanea), Iulian Antoniac, Aurora Antoniac, Dan Laptoiu, Gheorghe Paltanea, Robert Ciocoiu, Iosif Vasile Nemoianu, Lucian Gheorghe Gruionu, Horatiu Dura

Biomimetics· Volume 8· Issue 8

Abstract

Treatment of bone defects resulting after tumor surgeries, accidents, or non-unions is an actual problem linked to morbidity and the necessity of a second surgery and often requires a critical healthcare cost. Although the surgical technique has changed in a modern way, the treatment outcome is still influenced by patient age, localization of the bone defect, associated comorbidities, the surgeon approach, and systemic disorders. Three-dimensional magnesium-based scaffolds are considered an important step because they can have precise bone defect geometry, high porosity grade, anatomical pore shape, and mechanical properties close to the human bone. In addition, magnesium has been proven in in vitro and in vivo studies to influence bone regeneration and new blood vessel formation positively. In this review paper, we describe the magnesium alloy’s effect on bone regenerative processes, starting with a short description of magnesium’s role in the bone healing process, host immune response modulation, and finishing with the primary biological mechanism of magnesium ions in angiogenesis and osteogenesis by presenting a detailed analysis based on a literature review. A strategy that must be followed when a patient-adapted scaffold dedicated to bone tissue engineering is proposed and the main fabrication technologies are combined, in some cases with artificial intelligence for Mg alloy scaffolds, are presented with examples. We emphasized the microstructure, mechanical properties, corrosion behavior, and biocompatibility of each study and made a basis for the researchers who want to start to apply the regenerative potential of magnesium-based scaffolds in clinical practice. Challenges, future directions, and special potential clinical applications such as osteosarcoma and persistent infection treatment are present at the end of our review paper.
Source: crossref · Quality: baseline

Research context

OpenAlex topics: Magnesium Alloys: Properties and Applications · Bone Tissue Engineering Materials · Hydrogen Storage and Materials

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Faculty of Material Science and Engineering, National University of Science and Technology Politehnica Bucharest, 313 Splaiul Independentei, District 6, RO-060042 Bucharest, Romania

Faculty of Electrical Engineering, National University of Science and Technology Politehnica Bucharest, 313 Splaiul Independentei, District 6, RO-060042 Bucharest, Romania

Academy of Romanian Scientists, 54 Splaiul Independentei, RO-050094 Bucharest, Romania

Department of Orthopedics and Trauma I, Colentina Clinical Hospital, 19-21 Soseaua Stefan cel Mare, RO-020125 Bucharest, Romania

Faculty of Mechanics, University of Craiova, 13 Alexandru Ioan Cuza, RO-200585 Craiova, Romania

Faculty of Medicine, Lucian Blaga University of Sibiu, RO-550169 Sibiu, Romania

Funding

National Program for Research of the National Association of Technical Universities

References (100+)

Show source-provided references
1. The Use of Big Data to Improve Human Health: How Experience from Other Industries Will Shape the Future
2. Schulze, M., Gosheger, G., Bockholt, S., De Vaal, M., Budny, T., Tönnemann, M., Pützler, J., Bövingloh, A.S., Rischen, R., and Hofbauer, V. (2021). Complex Bone Tumors of the Trunk—The Role of 3D Printing and Navigation in Tumor Orthopedics: A Case Series and Review of the Literature. J. Pers. Med., 11.10.3390/jpm11060517 ↗
3. Amin, T., Parr, W.C.H., and Mobbs, R.J. (2021). Opinion Piece: Patient-Specific Implants May Be the Next Big Thing in Spinal Surgery. J. Pers. Med., 11.10.3390/jpm11060498 ↗
4. Savov, P., Tuecking, L.-R., Windhagen, H., and Ettinger, M. (2021). Individual Revision Knee Arthroplasty Is a Safe Limb Salvage Procedure. J. Pers. Med., 11.10.3390/jpm11060572 ↗
5. Beckenteilresektion (innere Hemipelvektomie) und endoprothetischer Ersatz bei hüftgelenksnahen Tumoren10.1007/s00064-012-0161-z ↗
6. Angelini, A., Piazza, M., Pagliarini, E., Trovarelli, G., Spertino, A., and Ruggieri, P. (2021). The Orthopedic-Vascular Multidisciplinary Approach Improves Patient Safety in Surgery for Musculoskeletal Tumors: A Large-Volume Center Experience. J. Pers. Med., 11.10.3390/jpm11060462 ↗
7. Pumilia, C.A., Schroeder, L., Sarpong, N.O., and Martin, G. (2021). Patient Satisfaction, Functional Outcomes, and Implant Survivorship in Patients Undergoing Customized Unicompartmental Knee Arthroplasty. J. Pers. Med., 11.10.3390/jpm11080753 ↗
8. Moret, C.S., Schelker, B.L., and Hirschmann, M.T. (2021). Clinical and Radiological Outcomes after Knee Arthroplasty with Patient-Specific versus Off-the-Shelf Knee Implants: A Systematic Review. J. Pers. Med., 11.10.3390/jpm11070590 ↗
9. Georgeanu, V.A., Gingu, O., Antoniac, I.V., and Manolea, H.O. (2023). Current Options and Future Perspectives on Bone Graft and Biomaterials Substitutes for Bone Repair, from Clinical Needs to Advanced Biomaterials Research. Appl. Sci., 13.10.3390/app13148471 ↗
10. Bone Grafts, Bone Substitutes and Orthobiologics10.4161/org.23306 ↗
11. Materials Design for Bone-Tissue Engineering10.1038/s41578-020-0204-2 ↗
12. Systematic Approach to the Management of Post-Traumatic Segmental Diaphyseal Long Bone Defects: Treatment Algorithm and Comprehensive Classification System10.5005/jp-journals-10080-1466 ↗
13. Interdisziplinäres Extremitäten-Board in der Behandlung von Komplexverletzungen10.1007/s00113-023-01290-4 ↗
14. Metallic Implant Biomaterials10.1016/j.mser.2014.10.001 ↗
15. Systemic Toxicity Related to Metal Hip Prostheses10.3109/15563650.2014.944977 ↗
16. Biodegradable Materials for Bone Defect Repair
17. Magnesium Alloys for Orthopedic Applications:A Review on the Mechanisms Driving Bone Healing10.1016/j.jma.2022.11.014 ↗
18. Biodegradable Polymers—An Overview10.1002/pat.3305 ↗
19. A Comprehensive Review on Biocompatible Mg-Based Alloys as Temporary Orthopaedic Implants: Current Status, Challenges, and Future Prospects10.1016/j.jma.2021.09.005 ↗
20. Biomimicking Bone–Implant Interface Facilitates the Bioadaption of a New Degradable Magnesium Alloy to the Bone Tissue Microenvironment10.1002/advs.202102035 ↗
21. Recent Progress in Mg-Based Alloys as a Novel Bioabsorbable Biomaterials for Orthopedic Applications10.1016/j.jma.2022.02.013 ↗
22. Long-Term Clinical Study and Multiscale Analysis of in Vivo Biodegradation Mechanism of Mg Alloy10.1073/pnas.1518238113 ↗
23. Biodegradable Mg Alloys for Orthopedic Implants—A Review10.1016/j.jma.2021.06.024 ↗
24. Porous Magnesium-Based Scaffolds for Tissue Engineering10.1016/j.msec.2016.11.027 ↗
25. Istrate, B., Munteanu, C., Antoniac, I.-V., and Lupescu, Ș.-C. (2022). Current Research Studies of Mg–Ca–Zn Biodegradable Alloys Used as Orthopedic Implants—Review. Crystals, 12.10.3390/cryst12101468 ↗
26. Vascularized Bone Grafting Fixed by Biodegradable Magnesium Screw for Treating Osteonecrosis of the Femoral Head10.1016/j.biomaterials.2015.11.038 ↗
27. Rau, J.V., Antoniac, I., Cama, G., Komlev, V.S., and Ravaglioli, A. (2016). Bioactive Materials for Bone Tissue Engineering. BioMed Res. Int., 2016.10.1155/2016/3741428 ↗
28. Potential of Biodegradable Magnesium Alloys for Medical Applications10.4028/p-r405h8 ↗
29. Paltanea, G., Manescu, V., Antoniac, I., Antoniac, A., Nemoianu, I.V., Robu, A., and Dura, H. (2023). A Review of Biomimetic and Biodegradable Magnetic Scaffolds for Bone Tissue Engineering and Oncology. Int. J. Mol. Sci., 24.10.3390/ijms24054312 ↗
30. Reddy, M.S.B., Ponnamma, D., Choudhary, R., and Sadasivuni, K.K. (2021). A Comparative Review of Natural and Synthetic Biopolymer Composite Scaffolds. Polymers, 13.10.3390/polym13071105 ↗
31. Antoniac, I., Miculescu, M., Mănescu, V., Stere, A., Quan, P.H., Păltânea, G., Robu, A., and Earar, K. (2022). Magnesium-Based Alloys Used in Orthopedic Surgery. Materials, 15.10.3390/ma15031148 ↗
32. Quan, P.H., Antoniac, I., Miculescu, F., Antoniac, A., Manescu, V., Robu, A., Bița, A.-I., Miculescu, M., Saceleanu, A., and Bodog, A.D. (2022). Fluoride Treatment and In Vitro Corrosion Behavior of Mg-Nd-Y-Zn-Zr Alloys Type. Materials, 15.10.3390/ma15020566 ↗
33. Scaffold Design for Bone Regeneration10.1166/jnn.2014.9127 ↗
34. Osteoblasts in Bone Tissue Engineering10.1243/09544119JEIM821 ↗
35. Buried Alive: How Osteoblasts Become Osteocytes10.1002/dvdy.20603 ↗
36. Non-Union Bone Fractures10.1038/s41572-021-00289-8 ↗
37. Inflammation, Fracture and Bone Repair10.1016/j.bone.2016.02.020 ↗
38. Aging, Inflammation, Stem Cells, and Bone Healing10.1186/s13287-016-0300-9 ↗
39. Boon and Bane of Inflammation in Bone Tissue Regeneration and Its Link with Angiogenesis10.1089/ten.teb.2014.0677 ↗
40. Modulating Macrophage Activities to Promote Endogenous Bone Regeneration: Biological Mechanisms and Engineering Approaches
41. Bone Physiological Microenvironment and Healing Mechanism: Basis for Future Bone-Tissue Engineering Scaffolds
42. The Biology of Fracture Healing10.1016/j.injury.2011.03.031 ↗
43. Zhao, T., Chu, Z., Ma, J., and Ouyang, L. (2022). Immunomodulation Effect of Biomaterials on Bone Formation. J. Funct. Biomater., 13.10.3390/jfb13030103 ↗
44. Immunomodulatory Bioactive Glasses for Tissue Regeneration10.1016/j.actbio.2021.08.023 ↗
45. Zn Content Mediated Fibrinogen Adsorption on Biodegradable Mg-Zn Alloys Surfaces10.1016/j.jma.2020.09.020 ↗
46. Influence of the Second Phase on Protein Adsorption on Biodegradable Mg Alloys’ Surfaces: Comparative Experimental and Molecular Dynamics Simulation Studies10.1016/j.actbio.2021.03.063 ↗
47. Bio-Adaption between Magnesium Alloy Stent and the Blood Vessel: A Review10.1016/j.jmst.2015.12.018 ↗
48. Additively Manufactured Biodegradable Porous Magnesium Implants for Elimination of Implant-Related Infections: An in Vitro and in Vivo Study
49. The in Vitro Biocompatibility and Macrophage Phagocytosis of Mg17Al12 Phase in Mg–Al–Zn Alloys10.1002/jbm.a.35374 ↗
50. Second Messenger Role for Mg2+ Revealed by Human T-Cell Immunodeficiency10.1038/nature10246 ↗
51. Rod-Shaped and Substituted Hydroxyapatite Nanoparticles Stimulating Type 1 and 2 Cytokine Secretion10.1016/j.colsurfb.2015.12.004 ↗
52. Comprehensive Study on the Roles of Released Ions from Biodegradable Mg–5 Wt% Ca–1 Wt% Zn Alloy in Bone Regeneration10.1002/term.2166 ↗
53. Inflammatory Response to Magnesium-Based Biodegradable Implant Materials10.1016/j.actbio.2019.10.014 ↗
54. Early Osteoimmunomodulatory Effects of Magnesium–Calcium–Zinc Alloys10.1177/20417314211047100 ↗
55. The Increased Ratio of Mg2+/Ca2+ from Degrading Magnesium Alloys Directs Macrophage Fate for Functionalized Growth of Endothelial Cells10.1016/j.smaim.2022.01.001 ↗
56. Macrophage-Derived Oncostatin M/Bone Morphogenetic Protein 6 in Response to Mg-Based Materials Influences pro-Osteogenic Activity of Human Umbilical Cord Perivascular Cells10.1016/j.actbio.2020.12.016 ↗
57. Peng, F., Cheng, S., Zhang, R., Li, M., Zhou, J., Wang, D., and Zhang, Y. (2021). Zn-Contained Mussel-Inspired Film on Mg Alloy for Inhibiting Bacterial Infection and Promoting Bone Regeneration. Regen. Biomater., 8.10.1093/rb/rbaa044 ↗
58. Improved Osteogenesis and Angiogenesis of Magnesium-Doped Calcium Phosphate Cement via Macrophage Immunomodulation10.1039/C6BM00290K ↗
59. Promoting Musculoskeletal System Soft Tissue Regeneration by Biomaterial-Mediated Modulation of Macrophage Polarization
60. In Vitro Immunomodulation of Magnesium on Monocytic Cell toward Anti-Inflammatory Macrophages10.1093/rb/rbaa010 ↗
61. A Biodegradable Mg-Based Alloy Inhibited the Inflammatory Response of THP-1 Cell-Derived Macrophages Through the TRPM7–PI3K–AKT1 Signaling Axis10.3389/fimmu.2019.02798 ↗
62. Magnesium and the Inflammatory Response: Potential Physiopathological Implications10.1016/j.abb.2006.03.031 ↗
63. Zhao, J., Wu, H., Wang, L., Jiang, D., Wang, W., Yuan, G., Pei, J., and Jia, W. (2022). The Beneficial Potential of Magnesium-Based Scaffolds to Promote Chondrogenesis through Controlled Mg2+ Release in Eliminating the Destructive Effect of Activated Macrophages on Chondrocytes. Biomater. Adv., 134.10.1016/j.msec.2022.112719 ↗
64. Phosphoinositide 3-Kinase/Akt Pathway Is Involved in Mediating the Anti-Inflammation Effects of Magnesium Sulfate10.1016/j.jss.2013.06.030 ↗
65. Properties and in Vitro Assessment of ZrO2-Based Coatings Obtained by Atmospheric Plasma Jet Spraying on Biodegradable Mg-Ca and Mg-Ca-Zr Alloys10.1016/j.ceramint.2020.03.138 ↗
66. Biodegradable Magnesium Alloys Promote Angio-Osteogenesis to Enhance Bone Repair10.1002/advs.202000800 ↗
67. Targeting Local Osteogenic and Ancillary Cells by Mechanobiologically Optimized Magnesium Scaffolds for Orbital Bone Reconstruction in Canines10.1021/acsami.0c00553 ↗
68. Biodegradable Mg-Cu Alloys with Enhanced Osteogenesis, Angiogenesis, and Long-Lasting Antibacterial Effects10.1038/srep27374 ↗
69. Magnesium Ion Stimulation of Bone Marrow Stromal Cells Enhances Osteogenic Activity, Simulating the Effect of Magnesium Alloy Degradation10.1016/j.actbio.2014.02.002 ↗
70. Localized Delivery of Growth Factors for Angiogenesis and Bone Formation in Tissue Engineering10.1016/j.intimp.2013.04.001 ↗
71. Multifunctions of Dual Zn/Mg Ion Co-Implanted Titanium on Osteogenesis, Angiogenesis and Bacteria Inhibition for Dental Implants10.1016/j.actbio.2016.11.067 ↗
72. Effect of Magnesium-Degradation Products and Hypoxia on the Angiogenesis of Human Umbilical Vein Endothelial Cells10.1016/j.actbio.2019.02.018 ↗
73. Chapter One—Biochemical and Biological Attributes of Matrix Metalloproteinases10.1016/bs.pmbts.2017.02.005 ↗
74. Mg–Zn–Mn Alloy Extract Induces the Angiogenesis of Human Umbilical Vein Endothelial Cells via FGF/FGFR Signaling Pathway10.1016/j.bbrc.2019.04.198 ↗
75. Magnesium Promotes Bone Formation and Angiogenesis by Enhancing MC3T3-E1 Secretion of PDGF-BB10.1016/j.bbrc.2020.05.113 ↗
76. Li, Y., Xu, J., Mi, J., He, X., Pan, Q., Zheng, L., Zu, H., Chen, Z., Dai, B., and Li, X. (2021). Biodegradable Magnesium Combined with Distraction Osteogenesis Synergistically Stimulates Bone Tissue Regeneration via CGRP-FAK-VEGF Signaling Axis. Biomaterials, 275.10.1016/j.biomaterials.2021.120984 ↗
77. PDGF-BB Secreted by Preosteoclasts Induces Angiogenesis during Coupling with Osteogenesis10.1038/nm.3668 ↗
78. Degradability and in Vivo Biocompatibility of Micro-Alloyed Mg-Ca-La Alloys as Orthopedic Implants10.1016/j.matlet.2021.131510 ↗
79. In Vitro and in Vivo Studies on As-Extruded Mg- 5.25wt.%Zn-0.6wt.%Ca Alloy as Biodegradable Metal10.1007/s40843-017-9205-x ↗
80. Improving in Vitro and in Vivo Corrosion Resistance and Biocompatibility of Mg–1Zn–1Sn Alloys by Microalloying with Sr
81. Wang, W.-H., Wang, F., Zhao, H.-F., Yan, K., Huang, C.-L., Yin, Y., Huang, Q., Chen, Z.-Z., and Zhu, W.-Y. (2020). Injectable Magnesium-Zinc Alloy Containing Hydrogel Complex for Bone Regeneration. Front. Bioeng. Biotechnol., 8.10.3389/fbioe.2020.617585 ↗
82. In Vitro and in Vivo Assessment of the Effect of Biodegradable Magnesium Alloys on Osteogenesis10.1016/j.actbio.2021.12.032 ↗
83. In Vitro and in Vivo Investigation on Biodegradable Mg-Li-Ca Alloys for Bone Implant Application10.1007/s40843-018-9293-8 ↗
84. Effects of Extracellular Magnesium Extract on the Proliferation and Differentiation of Human Osteoblasts and Osteoclasts in Coculture10.1016/j.actbio.2015.08.042 ↗
85. Osteogenic Effects of Bioabsorbable Magnesium Implant in Rat Mandibles and in Vitro10.1002/JPER.20-0162 ↗
86. Unraveling the Osteogenesis of Magnesium by the Activity of Osteoblasts in Vitro10.1039/C8TB01746H ↗
87. A Magnesium-Enriched 3D Culture System That Mimics the Bone Development Microenvironment for Vascularized Bone Regeneration10.1002/advs.201900209 ↗
88. Facile Distribution of an Alkaline Microenvironment Improves Human Bone Marrow Mesenchymal Stem Cell Osteogenesis on a Titanium Surface through the ITG/FAK/ALP Pathway10.1186/s40729-021-00341-y ↗
89. Role of pH—The Essential Step for Osteoporotic Bone Regeneration10.1016/j.bone.2010.09.298 ↗
90. Increased Osteoblast Viability at Alkaline pH in Vitro Provides a New Perspective on Bone Regeneration
91. Magnesium/Gallium-Layered Nanosheets on Titanium Implants Mediate Osteogenic Differentiation of MSCs and Osseointegration under Osteoporotic Condition10.1016/j.cej.2021.130982 ↗
92. Effect of Local Alkaline Microenvironment on the Behaviors of Bacteria and Osteogenic Cells10.1021/acsami.8b15724 ↗
93. Cell Adhesion on Surface-Functionalized Magnesium10.1021/acsami.6b01747 ↗
94. The Influence of Biodegradable Magnesium Implants on the Growth Plate10.1016/j.actbio.2017.11.031 ↗
95. Degradation of Bioresorbable Mg–4Zn–1Sr Intramedullary Pins and Associated Biological Responses in Vitro and in Vivo10.1021/acsami.7b15975 ↗
96. Hydrogen Inhibits the Osteoclastogenesis of Mouse Bone Marrow Mononuclear Cells10.1016/j.msec.2020.110640 ↗
97. Tuning Surface Properties of Bone Biomaterials to Manipulate Osteoblastic Cell Adhesion and the Signaling Pathways for the Enhancement of Early Osseointegration10.1016/j.colsurfb.2018.01.022 ↗
98. A Novel Biodegradable Mg-1Zn-0.5Sn Alloy: Mechanical Properties, Corrosion Behavior, Biocompatibility, and Antibacterial Activity10.1016/j.jma.2020.02.008 ↗
99. Mg2+ in β-TCP/Mg–Zn Composite Enhances the Differentiation of Human Bone Marrow Stromal Cells into Osteoblasts through MAPK-Regulated Runx2/Osx10.1002/jcp.29395 ↗
100. Stimulatory Effects of the Degradation Products from Mg-Ca-Sr Alloy on the Osteogenesis through Regulating ERK Signaling Pathway10.1038/srep32323 ↗