Magnesium Alloys in Orthopedics: A Systematic Review on Approaches, Coatings and Strategies to Improve Biocompatibility, Osteogenic Properties and Osteointegration Capabilities

There is increasing interest in using magnesium (Mg) alloy orthopedic devices because of their mechanical properties and bioresorption potential. Concerns related to their rapid degradation have been issued by developing biodegradable micro- and nanostructured coatings to enhance corrosion resistance and limit the release of hydrogen during degradation. This systematic review based on four databases (PubMed®, Embase, Web of Science™ and ScienceDirect®) aims to present state-of-the-art strategies, approaches and materials used to address the critical factors currently impeding the utilization of Mg alloy devices. Forty studies were selected according to PRISMA guidelines and specific PECO criteria. Risk of bias assessment was conducted using OHAT and SYRCLE tools for in vitro and in vivo studies, respectively. Despite limitations associated with identified bias, the review provides a comprehensive analysis of preclinical in vitro and in vivo studies focused on manufacturing and application of Mg alloys in orthopedics. This attests to the continuous evolution of research related to Mg alloy modifications (e.g., AZ91, LAE442 and WE43) and micro- and nanocoatings (e.g., MAO and MgF2), which are developed to improve the degradation rate required for long-term mechanical resistance to loading and excellent osseointegration with bone tissue, thereby promoting functional bone regeneration. Further research is required to deeply verify the safety and efficacy of Mg alloys.

[1]  G. Duda,et al.  Long-term in vivo observations show biocompatibility and performance of ZX00 magnesium screws surface-modified by plasma-electrolytic oxidation in Göttingen miniature pigs. , 2022, Acta biomaterialia.

[2]  Xianrong Zhang,et al.  Zinc-doped Ferric Oxyhydroxide Nano-layer Enhances the Bactericidal Activity and Osseointegration of a Magnesium Alloy through Augmenting the Formation of Neutrophil Extracellular Traps. , 2022, Acta biomaterialia.

[3]  Shi Cheng,et al.  Oxyhydroxide-Coated PEO–Treated Mg Alloy for Enhanced Corrosion Resistance and Bone Regeneration , 2022, Journal of functional biomaterials.

[4]  Oluwole K. Bowoto,et al.  A review of current challenges and prospects of magnesium and its alloy for bone implant applications , 2022, Progress in Biomaterials.

[5]  Zainen Qin,et al.  Hydroxyapatite/chitosan-metformin composite coating enhances the biocompatibility and osteogenic activity of AZ31 magnesium alloy , 2022, Journal of Alloys and Compounds.

[6]  I. Antoniac,et al.  Magnesium-Based Alloys Used in Orthopedic Surgery , 2022, Materials.

[7]  O. Kose,et al.  Bioabsorbable Magnesium Screw Fixation for Tibial Tubercle Osteotomy; A Preliminary Study , 2022, Acta bio-medica : Atenei Parmensis.

[8]  A. Vinogradov,et al.  On the Corrosion Fatigue of Magnesium Alloys Aimed at Biomedical Applications: New Insights from the Influence of Testing Frequency and Surface Modification of the Alloy ZK60 , 2022, Materials.

[9]  Peng Liu,et al.  Construction of multifunctional micro-patterned PALNMA/PDADMAC/PEGDA hydrogel and intelligently responsive antibacterial coating HA/BBR on Mg alloy surface for orthopedic application. , 2021, Materials science & engineering. C, Materials for biological applications.

[10]  A. Wennerberg,et al.  High-resolution ex vivo analysis of the degradation and osseointegration of Mg-xGd implant screws in 3D , 2021, Bioactive materials.

[11]  To Ngai,et al.  Polymer coatings on magnesium‐based implants for orthopedic applications , 2021, Journal of Polymer Science.

[12]  I. Rehman,et al.  Improving the in vitro Degradation, Mechanical and Biological Properties of AZ91-3Ca Mg Alloy via Hydrothermal Calcium Phosphate Coatings , 2021, Frontiers in Materials.

[13]  G. Duda,et al.  Improved in vivo osseointegration and degradation behavior of PEO surface-modified WE43 magnesium plates and screws after 6 and 12 months. , 2021, Materials science & engineering. C, Materials for biological applications.

[14]  M. Yao,et al.  Pure Mg–Al Layered Double Hydroxide Film on Magnesium Alloys for Orthopedic Applications , 2021, ACS omega.

[15]  Xinkun Shen,et al.  Osteoinduction Evaluation of Fluorinated Hydroxyapatite and Tantalum Composite Coatings on Magnesium Alloys , 2021, Frontiers in Chemistry.

[16]  Puneet Katyal,et al.  Effects of alloying elements on performance of biodegradable magnesium alloy , 2021, Materials Today: Proceedings.

[17]  A. Cochis,et al.  Osteosynthesis devices in absorbable Magnesium alloy in comparison to standard ones: a Systematic Review on effectiveness and safety , 2021, Acta bio-medica : Atenei Parmensis.

[18]  Cecilia Prata,et al.  Magnesium: Biochemistry, Nutrition, Detection, and Social Impact of Diseases Linked to Its Deficiency , 2021, Nutrients.

[19]  E. Mayo-Wilson,et al.  The PRISMA 2020 statement: An updated guideline for reporting systematic reviews , 2021, PLoS medicine.

[20]  G. Yuan,et al.  Effects of composition and hierarchical structures of calcium phosphate coating on the corrosion resistance and osteoblast compatibility of Mg alloys. , 2021, Materials science & engineering. C, Materials for biological applications.

[21]  M. Costache,et al.  In Vitro Macrophage Immunomodulation by Poly(ε-caprolactone) Based-Coated AZ31 Mg Alloy , 2021, International journal of molecular sciences.

[22]  R. Misra,et al.  The effect of different coatings on bone response and degradation behavior of porous magnesium-strontium devices in segmental defect regeneration , 2020, Bioactive materials.

[23]  Hyoung-Seop Kim,et al.  Biocompatible Magnesium Implant Double-Coated with Dexamethasone-Loaded Black Phosphorus and Poly(lactide-co-glycolide). , 2020, ACS applied bio materials.

[24]  P. Wriggers,et al.  Influence of coatings on degradation and osseointegration of open porous Mg scaffolds in vivo , 2020 .

[25]  H. Lee,et al.  Construction of tantalum/poly(ether imide) coatings on magnesium implants with both corrosion protection and osseointegration properties , 2020, Bioactive materials.

[26]  Donghui Wang,et al.  Zn-contained mussel-inspired film on Mg alloy for inhibiting bacterial infection and promoting bone regeneration , 2020, Regenerative biomaterials.

[27]  Xuanyong Liu,et al.  Osteogenesis, angiogenesis and immune response of Mg-Al layered double hydroxide coating on pure Mg , 2020, Bioactive materials.

[28]  Ulrich Dirnagl,et al.  The ARRIVE guidelines 2.0: updated guidelines for reporting animal research , 2020, The Journal of physiology.

[29]  Ulrich Dirnagl,et al.  The ARRIVE guidelines 2.0: Updated guidelines for reporting animal research* , 2020, BMC Veterinary Research.

[30]  C. Gu,et al.  Advances in coatings on biodegradable magnesium alloys , 2020 .

[31]  P. Wriggers,et al.  Comparison of degradation behaviour and osseointegration of the two magnesium scaffolds, LAE442 and La2, in vivo , 2019 .

[32]  G. Thevendran,et al.  Magnesium-based bioabsorbable screw fixation for hallux valgus surgery - A suitable alternative to metallic implants. , 2019, Foot and ankle surgery : official journal of the European Society of Foot and Ankle Surgeons.

[33]  Yufeng Zheng,et al.  In vitro and in vivo studies of Mg-30Sc alloys with different phase structure for potential usage within bone. , 2019, Acta biomaterialia.

[34]  Yufeng Zheng,et al.  A functionalized TiO2/Mg2TiO4 nano-layer on biodegradable magnesium implant enables superior bone-implant integration and bacterial disinfection. , 2019, Biomaterials.

[35]  W. Lu,et al.  One-pot hydrothermal synthesis, in vitro biodegradation and biocompatibility of Sr-doped nanorod/nanowire hydroxyapatite coatings on ZK60 magnesium alloy , 2019, Journal of Alloys and Compounds.

[36]  Natalie S Blencowe,et al.  RoB 2: a revised tool for assessing risk of bias in randomised trials , 2019, BMJ.

[37]  Chao Yang,et al.  Lithium-Incorporated Nanoporous Coating Formed by Micro Arc Oxidation (MAO) on Magnesium Alloy with Improved Corrosion Resistance, Angiogenesis and Osseointegration. , 2019, Journal of biomedical nanotechnology.

[38]  Min-Ho Lee,et al.  Enhancement of bone formation on LBL-coated Mg alloy depending on the different concentration of BMP-2. , 2019, Colloids and surfaces. B, Biointerfaces.

[39]  M. Doble,et al.  Nanostructure coated AZ31 magnesium cylindrical mesh cage for potential long bone segmental defect repair applications. , 2018, Colloids and surfaces. B, Biointerfaces.

[40]  F. Witte,et al.  Biodegradable Metals , 2018, Biomaterials Science.

[41]  Yufeng Zheng,et al.  Osteoimmunomodulation, osseointegration, and in vivo mechanical integrity of pure Mg coated with HA nanorod/pore-sealed MgO bilayer. , 2018, Biomaterials science.

[42]  James F Curtin,et al.  Effect of High- and Low-Molecular-Weight Hyaluronic-Acid-Functionalized-AZ31 Mg and Ti Alloys on Proliferation and Differentiation of Osteoblast Cells. , 2018, ACS biomaterials science & engineering.

[43]  Shu Cai,et al.  Biomimetic fluoridated hydroxyapatite coating with micron/nano-topography on magnesium alloy for orthopaedic application , 2018 .

[44]  Yufeng Zheng,et al.  Development of magnesium-based biodegradable metals with dietary trace element germanium as orthopaedic implant applications. , 2017, Acta biomaterialia.

[45]  V. Thakur,et al.  Cellulose acetate membranes functionalized with resveratrol by covalent immobilization for improved osseointegration , 2017 .

[46]  Ke Yang,et al.  Comparison study of different coatings on degradation performance and cell response of Mg-Sr alloy. , 2016, Materials science & engineering. C, Materials for biological applications.

[47]  Xianlong Zhang,et al.  Dual ions implantation of zirconium and nitrogen into magnesium alloys for enhanced corrosion resistance, antimicrobial activity and biocompatibility. , 2016, Colloids and surfaces. B, Biointerfaces.

[48]  H. Wiltsche,et al.  Effects of Corroded and Non-Corroded Biodegradable Mg and Mg Alloys on Viability, Morphology and Differentiation of MC3T3-E1 Cells Elicited by Direct Cell/Material Interaction , 2016, PloS one.

[49]  Diego Mantovani,et al.  Long-term clinical study and multiscale analysis of in vivo biodegradation mechanism of Mg alloy , 2016, Proceedings of the National Academy of Sciences.

[50]  M. Rovers,et al.  SYRCLE’s risk of bias tool for animal studies , 2014, BMC Medical Research Methodology.

[51]  S. Stanzl-Tschegg,et al.  Comparative biomechanical and radiological characterization of osseointegration of a biodegradable magnesium alloy pin and a copolymeric control for osteosynthesis. , 2013, Journal of the mechanical behavior of biomedical materials.

[52]  C. Stukenborg-Colsman,et al.  Biodegradable magnesium-based screw clinically equivalent to titanium screw in hallux valgus surgery: short term results of the first prospective, randomized, controlled clinical pilot study , 2013, Biomedical engineering online.

[53]  Daljit Singh,et al.  Functional outcome of ankle fracture patients treated with biodegradable implants. , 2012, Foot and ankle surgery : official journal of the European Society of Foot and Ankle Surgeons.

[54]  S. Bhat Orthopaedic Implants , 2000 .

[55]  Yufeng Zheng,et al.  A self-healing coating containing curcumin for osteoimmunomodulation to ameliorate osseointegration , 2021, Chemical Engineering Journal.

[56]  Ke Yang,et al.  In vitro and in vivo evaluation of MgF2 coated AZ31 magnesium alloy porous scaffolds for bone regeneration. , 2017, Colloids and surfaces. B, Biointerfaces.