In vitro and in vivo degradation behavior of Mg-0.45Zn-0.45Ca (ZX00) screws for orthopedic applications

Martinez, Diana C.; Dobkowska, Anna; Marek, Romy; Ćwieka, Hanna; Jaroszewicz, Jakub; Płociński, T.; Donik, Črtomir; Helmholz, Heike; Luthringer-Feyerabend, Bérengère; Zeller‐Plumhoff, Berit; Willumeit‐Römer, Regine; Święszkowski, Wojciech

doi:10.1016/j.bioactmat.2023.05.004

Cited by 11 publications

(5 citation statements)

References 153 publications

(256 reference statements)

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“…The rapid degradation rate of Mg‐based materials leads to a sharp decline in mechanical properties, and the generation of excessive hydrogen gas alkalizes the local microenvironment, affecting tissue healing. [ 36 ] Fe‐based alloys degrade slowly, and their ferromagnetism interferes with the radiological examination. Zn‐based alloys have degradation rates that better match the bone‐healing cycle than those of Fe‐ and Mg‐based alloys, making them more suitable as fracture‐fixation materials.…”

Section: Discussionmentioning

confidence: 99%

Biodegradable Zn‐5Dy Alloy with Enhanced Osteo/Angio‐Genic Activity and Osteointegration Effect via Regulation of SIRT4‐Dependent Mitochondrial Function

Han,

Tong,

Zhou

et al. 2024

Advanced Science

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Zinc (Zn)–dysprosium (Dy) binary alloys are promising biodegradable bone fracture fixation implants owing to their attractive biodegradability and mechanical properties. However, their clinical application is a challenge for bone fracture healing, due to the lack of Zn–Dy alloys with tailored proper bio‐mechanical and osteointegration properties for bone regeneration. A Zn‐5Dy alloy with high strength and ductility and a degradation rate aligned with the bone remodeling cycle is developed. Here, mechanical stability is further confirmed, proving that Zn‐5Dy alloy can resist aging in the degradation process, thus meeting the mechanical requirements of fracture fixation. In vitro cellular experiments reveal that the Zn‐5Dy alloy enhances osteogenesis and angiogenesis by elevating SIRT4‐mediated mitochondrial function. In vivo Micro‐CT, SEM‐EDS, and immunohistochemistry analyses further indicate good biosafety, suitable biodegradation rate, and great osteointegration of Zn‐5Dy alloy during bone healing, which also depends on the upregulation of SIRT4‐mediated mitochondrial events. Overall, the study is the first to report a Zn‐5Dy alloy that exerts remarkable osteointegration properties and has a strong potential to promote bone healing. Furthermore, the results highlight the importance of mitochondrial modulation and shall guide the future development of mitochondria‐targeting materials in enhancing bone fracture healing.

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Section: Discussionmentioning

confidence: 99%

Biodegradable Zn‐5Dy Alloy with Enhanced Osteo/Angio‐Genic Activity and Osteointegration Effect via Regulation of SIRT4‐Dependent Mitochondrial Function

Han,

Tong,

Zhou

et al. 2024

Advanced Science

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“…In the studies of Marek et al., , Mg-based alloy ZX00 (Mg < 0.5 Zn < 0.5 Ca, in wt %) was implanted in sheep tibia, and the osteointegration potential as well as biodegradation were studied radiologically and histopathologically. In another study, Mg-0.45Zn-0.45Ca (ZX00) screws were implanted in sheep tibia again, and the osteogenic potential as well as the degradation profile were assessed. To the best of our knowledge, this study is novel in terms of investigating the vascularized bone regeneration (osteogenic and angiogenic) potential of Mg-based implants in a sheep cranial defect model, which is important to assess the bone–implant interactions free of biomechanical stresses.…”

Section: Discussionmentioning

confidence: 99%

MgCa-Based Alloys Modified with Zn- and Ga-Doped CaP Coatings Lead to Controlled Degradation and Enhanced Bone Formation in a Sheep Cranium Defect Model

Gokyer,

Monsef,

Buyuksungur

et al. 2024

ACS Biomater. Sci. Eng.

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Mg-based biodegradable metallic implants are gaining increased attraction for applications in orthopedics and dentistry. However, their current applications are hampered by their high rate of corrosion, degradation, and rapid release of ions and gas bubbles into the physiological medium. The aim of the present study is to investigate the osteogenic and angiogenic potential of coated Mg-based implants in a sheep cranial defect model. Although their osteogenic potential was studied to some extent, their potential to regenerate vascularized bone formation was not studied in detail. We have studied the potential of magnesium−calcium (MgCa)-based alloys modified with zinc (Zn)-or gallium (Ga)-doped calcium phosphate (CaP) coatings as a strategy to control their degradation rate while enhancing bone regeneration capacity. MgCa and its implants with CaP coatings (MgCa/CaP) as undoped or as doped with Zn or Ga (MgCa/CaP + Zn and MgCa/CaP + Ga, respectively) were implanted in bone defects created in the sheep cranium. MgCa implants degraded faster than the others at 4 weeks postop and the weight loss was ca. 50%, while it was ca. 15% for MgCa/CaP and <10% in the presence of Zn and Ga with CaP coating. Scanning electron microscopy (SEM) analysis of the implant surfaces also revealed that the MgCa implants had the largest degree of structural breakdown of all the groups. Radiological evaluation revealed that surface modification with CaP to the MgCa implants induced better bone regeneration within the defects as well as the enhancement of bone−implant surface integration. Bone volume (%) within the defect was ca. 25% in the case of MgCa/CaP + Ga, while it was around 15% for undoped MgCa group upon micro-CT evaluation. This >1.5-fold increase in bone regeneration for MgCa/CaP + Ga implant was also observed in the histopathological examination of the H&E-and Masson's trichrome-stained sections. Immunohistochemical analysis of the bone regeneration (antiosteopontin) and neovascularization (anti-CD31) at the defect sites revealed >2-fold increase in the expression of the markers in both Ga-and Zn-doped, CaP-coated implants. Zn-doped implants further presented low inflammatory reaction, notable bone regeneration, and neovascularization among all the implant groups. These findings indicated that Ga-and Zn-doped CaP coating is an important strategy to control the degradation rate as well as to achieve enhanced bone regeneration capacity of the implants made of Mg-based alloys.

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“…Investigations into the in vitro [ 20,21,25–30 ] and in vivo [ 22,31–33 ] degradation behavior on the macro‐ and centimeter‐scale have been numerous. It has been reported that the addition of Zn can stabilize the otherwise rapid degradation of Mg. [ 34–37 ] The corrosion rates are highly dependent on various parameters, such as the material purity, shape, and composition, as well as the surrounding medium, pH, fluid flows, etc., but overall Mg is expected to degrade two to twenty times faster than Zn.…”

Section: Introductionmentioning

confidence: 99%

Degradable and Biocompatible Magnesium Zinc Structures for Nanomedicine: Magnetically Actuated Liposome Microcarriers with Tunable Release

Peter,

Kadiri,

Goyal

et al. 2024

Adv Funct Materials

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Inorganic therapeutic carriers and implants should not only be biocompatible, but should also degrade under physiological conditions. Ideally, the time of the degradation can be controlled, and ideally the degradation products are fully biocompatible and metabolized by the body. This proves a challenge for carriers used in nanomedicine, including microswimmers and nanorobotic systems destined for targeted delivery, as these generally require inorganic materials to enable coupling to external fields. Taking inspiration from macroscopic orthopedic implants that are made from magnesium (Mg) and zinc (Zn) and that are fully biocompatible and degradable, it is showed the growth of complex microstructures, including micropropellers, containing Mg and Zn. By varying the content of Mg, the corrosion time of the microstructures can be tuned from hours to over a month. Incorporation of biocompatible hard‐magnetic iron (Fe)‐platinum (Pt) permits the controlled motion of the micropropellers. The surface of the MgZn structures can be functionalized with liposomes, rendering the structures microcarriers that allow for a time‐dependent release of their cargo as a results of their degradation in aqueous environments. This suggests a powerful platform for targeted drug or gene delivery, that can be integrated with established systems for magnetic actuation and transfection.

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In vitro and in vivo degradation behavior of Mg-0.45Zn-0.45Ca (ZX00) screws for orthopedic applications

Cited by 11 publications

References 153 publications

Biodegradable Zn‐5Dy Alloy with Enhanced Osteo/Angio‐Genic Activity and Osteointegration Effect via Regulation of SIRT4‐Dependent Mitochondrial Function

Biodegradable Zn‐5Dy Alloy with Enhanced Osteo/Angio‐Genic Activity and Osteointegration Effect via Regulation of SIRT4‐Dependent Mitochondrial Function

MgCa-Based Alloys Modified with Zn- and Ga-Doped CaP Coatings Lead to Controlled Degradation and Enhanced Bone Formation in a Sheep Cranium Defect Model

Degradable and Biocompatible Magnesium Zinc Structures for Nanomedicine: Magnetically Actuated Liposome Microcarriers with Tunable Release

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