Temporary Implants Research Articles

Ceria-based coatings on magnesium alloys for biomedical applications: a literature review.

Magnesium alloys are being studied for use in temporary orthopedic implants because of their mechanical properties, which are similar to those of human bone, and their good biocompatibility. However, their application is limited due to their rapid degradation, and early loss of their mechanical properties, decreasing the stability of the implant and its proper synchronization with tissue regeneration. In this regard, various surface coatings have been used to improve their biological, physico-chemical and biodegradation properties. Currently, one of the most explored strategies is using smart coatings because of their self-healing properties that can slow down the corrosion process of Mg and its alloys. Ceria-based materials show promise as coatings for these alloys. Their unique redox capacity not only provides Mg alloys with good self-healing properties but also interesting biological properties, which are described in this paper. Despite this, some problems and challenges related to the biocompatibility and application of these materials in coatings remain unsolved. In this article, a critical review is presented summarizing the most representative literature on ceria-based coatings on Mg alloys for their potential use as biomaterials. The results show that ceria is a versatile material that may be used in industrial and biomedical applications.

The Evaluation of a Cost-Effective Method for Tumour Marking Prior to Neo-Adjuvant Chemotherapy Using Silver Rods.

The lack of objective documentation of pre-neoadjuvant chemotherapy (NAC) tumour margins is a major constraint in performing safe breast conserving surgery (BCS) in patients with breast cancer. Using a novel method of marking pre-NACT tumour margins with indigenous silver wire markers, this retrospective observational study attempted to assess the feasibility of safe BCS in breast cancer patients by performing excision wide of the marked pre-NACT margins. This retrospective observational study was conducted on breast cancer patients who were attending our oncology centre between May, 2015 and April, 2022. All patients had received NAC followed by surgery as recommended by our multidisciplinary team. All the patients had a primary operable solitary breast cancer. We used radiopaque metallic rods made from silver to localize tumour margins prior to NAC. Sixty-four breast cancer patients were included; none had marker-related complications. Following NAC, BCS could be easily performed in 60 patients guided by the silver markers, which were used as temporary implants and removed during surgery. Only 2 patients were seen with positive margins and were converted to mastectomy. Breast cancer localization using sterile silver markers before the initiation of NAC is safe, easy, inexpensive, and effective, causing no morbidity or significant pain to the patients.

Biodegradable Materials for Transient Organic Transistors

AbstractElectronic devices that can physically disappear in a controlled manner without harmful by‐products unveil a wide range of opportunities in medical devices, environmental monitoring, and next‐generation consumer electronics. Their property of transience is indispensable for mitigating the global problem of electronic waste accumulation. Additionally, transient technologies that are biocompatible and can be biologically resorbed are of great potential for applications in temporary medical implants, since it eliminates the need for expensive device recovery surgery. Transistors are the key building blocks of modern electronics, and their fabrication using organic materials is beneficial due to their low cost, unprecedented flexibility and facile processing. This contribution reviews the technological application of biodegradable materials in four major classes of organic transistors, namely organic field‐effect transistors (OFETs), organic synaptic transistors, electrolyte‐gated OFETs, and organic electrochemical transistors. The fundamental biodegradation mechanism is discussed in detail, followed by a perspective of various biodegradable materials utilized as active semiconductors, dielectrics, electrolytes and substrates in the various types of organic transistor devices. This contribution comprehensively discusses the role and application of biodegradable materials in all of the key modern‐day organic transistors, highlighting their unique properties that allow the fabrication of biodegradable, eco‐friendly, and sustainable devices.

Finite element simulations of mechanical behaviour and degradation of iron lattices

Biodegradable metals such as iron have become appealing for usage in temporary bone implants. Although iron possesses excellent properties of biocompatibility, it shows a very slow degradation rate and presents a higher stiffness and strength when compared to human bone. Several strategies can be applied to decrease the strength of the iron, one of them being the use of porous/cellular structures. The present work aims to study the mechanical properties and the degradation behaviour of porous iron with cellular structures composed of lattice struts. Six lattice geometries, which were previously studied, and inspired by crystalline structures, were designed. The mechanical behaviour of the lattice arrangements was studied numerically using the finite element software NX Nastran. The corrosion module of the finite element software COMSOL was used to simulate the degradation behaviour of the cellular structure immersed in simulated body fluid. After the degradation process, the compressive properties of the porous cellular structures were also assessed. Under compression, the iron lattice structures showed an elastic limit stress close to the values determined for the trabecular bone yield stress. Geometries selected to simulate degradation have shown mass loss percentage and corrosion rates close to the degradation rate established for an ideal bone substitute. The present study confirms that the structural arrangement has a strong influence on the mechanical properties of iron cellular structures. The degradation behaviour of iron lattices also appears to be affected by the unit cell topology.

Oxygen-sensitive nanoparticles reveal the spatiotemporal dynamics of oxygen reduction during magnesium implant biodegradation

Magnesium (Mg) alloys are becoming increasingly important in the biomedical field as temporary bone implants. However, the biodegradation process of Mg alloys is highly complex and recent findings suggest that oxygen (O2) consumption is non-negligible. In this study, we give experimental proof of O2 consumption during Mg degradation under physiological conditions. Specifically, we study pure Mg, Mg–6 wt%Ag and Mg–5 wt%Gd in Hanks’ balanced salt solution and Dulbecco’s modified Eagle’s medium. We show that O2 consumption and hydrogen evolution are inversely correlated and that O2 concentrations remain below 7.5% in certain cases, which could have significant implications for bone healing.

PEO/Polymer hybrid coatings on magnesium alloy to improve biodegradation and biocompatibility properties

There is an increasing tendency towards replacing permanent implants with biodegradable magnesium implants in temporary bone applications like screws and pins. This inclination arises from the close mechanical properties and biocompatibility of magnesium (Mg) to bone. Nonetheless, the high degradation rate of Mg can be a reason for implant loosening even in the early weeks after implantation. This study aims to design a multifunctional multilayered coating based on a combination of inorganic and organic layers for controlling the degradation behaviour. An inorganic layer was created on the substrate of magnesium alloy, AZ31B Mg, via plasma electrolytic oxidation (PEO) process while an organic layer of elastic poly trimethylene carbonate (PTMC) polymer was deposited by dip coating in the vacuum condition to have open pores of the PEO layer sealed. Subsequently, the coating was functionalized with a biomimetic polydopamine layer. The electrochemical corrosion measurements in simulated body fluid (SBF) showed the resistance against corrosion increases after deposition of the polydopamine functionalized PTMC on the PEO layer. In-vitro investigations in SBF evaluated the bioactivity of the multilayered coating. Moreover, MTT assays did not show cytotoxicity in the coating. Cell culture evaluations helped to determine the cell spreading and adhesion on the multilayered coating. Based on our findings, the fabricated layered composite on the biodegradable AZ31B alloy would add privileges to the sector of temporary implants.

Enhancing the corrodibility of biodegradable iron and zinc using poly(lactic) acid (PLA) coating for temporary medical implant applications

Iron (Fe) and zinc (Zn) are attractive materials for fabricating temporary implants. However, for some applications, the use of these materials is limited by their relatively slow corrosion rates. This study investigates the use of poly(lactic) acid (PLA) coating to control corrosion rates of biodegradable pure Fe and Zn in a physiological environment. PLA accelerated the degradation of both Fe and Zn, attributed to the occurrence of localized acidic environments at the metal-coating interface generated by the hydrolytic decomposition of the polymer. Corrosion enhancement favoured an amorphous polymer structure (poly (dl-lactide)), low molecular weight, and thicker coatings. Polarization and immersion tests indicated an optimum coating thickness (Fe = 15 μm, Zn = 10 μm) at which maximum corrosion acceleration is achieved, as determined by the interaction of the rate of polymer hydrolysis and metal surface passivation.

Corrosion processes of sintered materials based on Fe

All currently used metal-based implants have the disadvantage of often requiring secondary surgery to remove the implant. This is why there is a lot of research into biodegradable bone implants these days. Biodegradable iron-based alloys are potential candidates for use as materials for temporary implants. This work deals with the current topic of Fe-based biodegradable sintered materials and their corrosion. These materials are suitable for applications where gradual decomposition is required. Sintered materials based on Fe-Mg are investigated in this work. The manufactured samples were immersed in NaCl solution and simulated body fluid – SBF. Subsequently, changes in corrosion potential and current, pH, conductivity and observations under the microscope were regularly analysed.

In vitro characterization of anodized magnesium alloy as a potential biodegradable material for biomedical applications

Pure metals and their alloys are used to partially or completely restore bone fractures. Biodegradable metals emerged as promising candidates for fracture fixation devices since they are able to self-degrade in the body environment. The main challenge of the devices is to reach an adequate degradation rate relative to the bone healing and also to present safe degradation by-products. Magnesium alloys are very much studied because of their promising properties, but the main limitation for their application in biomedical devices is the hydrogen evolution that results from their corrosion in aqueous media. This work assesses the effects of low potential anodizing process of AZ91 alloys in basic media on surface topography, electrochemical response, hydrogen evolution and cell attachment compared with the non-treated alloys. A comparative approach to determine the electrochemical parameters for assessing the degradation rate is also discussed. Results show that the electrochemical treatment of anodizing at low voltage in 5 mol/L KOH solution generates magnesium oxide/hydroxide on the surface which could act as a barrier to prevent fast degradation, and consequently to reduce hydrogen release. In turn, this treatment improved the adhesion of bovine embryonic fibroblasts (BEFs) and MCT3T3 pre-osteoblastic cells to the surface, showing that it could be a good candidate to be used in temporary implants.

Experimental Characterization and Numerical Modeling of the Corrosion Effect on the Mechanical Properties of the Biodegradable Magnesium Alloy WE43 for Orthopedic Applications.

Computational modeling plays an important role in the design of orthopedic implants. In the case of biodegradable magnesium alloys, a modeling approach is required to predict the effects of degradation on the implant’s capacity to provide the desired stabilization of fractured bones. In the present work, a numerical corrosion model is implemented to predict the effects of biodegradation on the structural integrity of temporary trauma implants. A non-local average pitting corrosion model is calibrated based on experimental data collected from in vitro degradation experiments and mechanical testing of magnesium WE43 alloy specimens at different degradation stages. The localized corrosion (pitting) model was implemented by developing a user material subroutine (VUMAT) with the program Abaqus®/Explicit. In order to accurately capture both the linear mechanical reduction in specimen resistance, as well as the non-linear corrosion behavior of magnesium WE43 observed experimentally, the corrosion model was extended by employing a variable corrosion kinetic parameter, which is time-dependent. The corrosion model was applied to a validated case study involving the pull-out test of orthopedic screws and was able to capture the expected loss of screw pull-out force due to corrosion. The proposed numerical model proved to be an efficient tool in the evaluation of the structural integrity of biodegradable magnesium alloys and bone-implant assembly and can be used in future works in the design optimization and pre-validation of orthopedic implants.

(Digital Presentation) Electrodeposition of Thin Films of Femn Alloys for Biodegradable Scaffolds Fabrication

Biodegradable metallic scaffolds are interesting biomaterials for applications in temporary implants for bone regeneration because of their good mechanical properties. In addition, the need for a second surgery to remove the implant is reduced if biodegradable metals are used. Fe has adequate mechanical properties for scaffolds manufacture and suitable biocompatibility. However, Fe shows slow biodegradation rates for the application and, therefore, different approaches have been developed such as the development of alloys or by reducing the thickness of the Fe strut in the scaffold. FeMn alloys are considered ideal materials, as they are not ferromagnetic. In addition, additive manufacturing technologies (3D printing) are considered appropriate to manufacture these scaffolds due to the ability to obtain complicated geometries and customized parts for a specific bone injury site. Electrodeposition is also an interesting technique because it allows the deposition of thinner strut walls of Fe (or alloys) with high purity, in addition to providing a good surface finishing. The aim of the first part of this work is to electrodeposit thin films of FeMn alloys and to evaluate its microstructure and mechanical properties. The thin films were electrodeposited potentiostatically from sulfate electrolytes with different concentrations of FeSO4 and MnSO4. The effect of deaeration, substrate material and electrodeposition potential were evaluated. The microstructure of the electrodeposited films was characterized by SEM/EDX and XRD. The surface finishing was evaluated by AFM and the mechanical properties by microhardness measurements.

Nanolaminated HfO2/Al2O3 Dielectrics for High‐Performance Silicon Nanomembrane Based Field‐Effect Transistors on Biodegradable Substrates

AbstractEmerging transient electronics offer great potential in eco‐friendly and bioresorbable electronic applications. In this study, bendable and biodegradable metal‐oxide‐semiconductor field‐effect transistors (MOSFETs) and metal‐oxide‐semiconductor capacitors (MOSCAPs) have been fabricated by integrating HfO2/Al2O3 high‐k bilayers on the transferred silicon nanomembranes (Si NMs) and utilizing PLGA‐gelatin‐chitosan polymeric substrates. The transient n‐channel MOSFETs demonstrate high effective mobility of 871 cm2 V−1 s−1, high on‐state current of 27.6 µA µm−1, high on/off current ratio > 107, and low gate leakage current ≤2.7 × 10−7 A cm−2. The accumulation capacitance of the transient MOSCAPs exceeds 6.5 × 10−7 F cm−2, indicating an enhanced gate control over the Si NM channel. The presented excellent performance is on par with the highest performance of the reported transient devices. Accelerated soaking tests in aqueous environments combined with systematic studies of the electrical characteristics as a function of the transience stage reveal the dissolution chemistry and kinetics of the biodegradable devices associated with the underlying transient behaviors. Moreover, detailed analysis of mechanics provides insights into the optimized device‐grade geometries for precise control of the functional lifetimes. These results will be beneficial to paving a realistic path for achieving high‐performance and on‐demand water‐soluble Si NM based MOSFETs toward futuristic applications in disposable electronics and temporary biomedical implants.

Ultra-low Young's modulus Zr-Nb thin films on Mg substrate for enhanced corrosion resistance

Controlling the degradation rate of magnesium (Mg) via applying the (Zr-Nb) thin films was investigated in this study. The Zr-2.5Nb coatings were deposited on the Mg with thicknesses of 250, 450, 650, and 900 nm (hereafter named [email protected], [email protected], [email protected], and [email protected]), respectively. Grazing incidence angle X-ray diffraction of (Zr-Nb) coatings revealed the alpha phase of zirconium and dominant (002) texture, with the film thickness increasing from 450 nm to 900 nm. Potentiodynamic polarization, electrochemical impedance spectroscopy, and corrosion morphology observations in Dulbecco's Modified Eagle's cell culture medium (DMEM) solution revealed the (Zr-2.5Nb)-coated mg with the thickness of [email protected] sample provides the highest corrosion resistance compared to other studied thicknesses. [email protected] sample increases the corrosion potential from −1.49 V to −1.38 V and decreases the current corrosion density and corrosion rate from 149.32 (μA.cm−2) to 39.01 (μA.cm−2) and from 3.49 (mm.y−1) to 0.912 (mm.y−1), respectively. Further studies on the surface of the [email protected] sample in terms of nano-mechanical properties demonstrated that Young's modulus and hardness are 47.95± 4.43 GPa and 2.25± 0.41 GPa, respectively, which increases the hardness to reduced Young's modulus ratio, which is known as one of the important parameters in developing of temporary orthopedic implants, of the Mg from 0.03 to 0.06. Furthermore, nano-tribological measurements and atomic force microscopy observations confirmed that detachment or breakage are not observed. Zr-2.5Nb coating, owing to the influence only on the first stage of the degradation reduced the degradation rate of Mg surafce, and therefore, can be considered as a practical strategy for further development of Mg in orthopedic applications.

GEC-ESTRO ACROP recommendations on calibration and traceability of HE HDR-PDR photon-emitting brachytherapy sources at the hospital level

The vast majority of radiotherapy departments in Europe using brachytherapy (BT) perform temporary implants of high- or pulsed-dose rate (HDR-PDR) sources with photon energies higher than 50 keV. Such techniques are successfully applied to diverse pathologies and clinical scenarios. These recommendations are the result of Working Package 21 (WP-21) initiated within the BRAchytherapy PHYsics Quality Assurance System (BRAPHYQS) GEC-ESTRO working group with a focus on HDR-PDR source calibration. They provide guidance on the calibration of such sources, including practical aspects and issues not specifically accounted for in well-accepted societal recommendations, complementing the BRAPHYQS WP-18 Report dedicated to low energy BT photon emitting sources (seeds). The aim of this report is to provide a European-wide standard in HDR-PDR BT source calibration at the hospital level to maintain high quality patient treatments.

Temporary Protective Shoulder Implants for Revision Surgery with Bone Glenoid Grafting.

This article describes the development of a temporary protective glenoid prosthesis placed between the augmentation and humeral head prosthesis during the healing phase of shoulder prosthesis revision with necessary reconstruction of the bony structure of the glenoid. The glenoid protection prosthesis ensures the fixation of the augmentation material and protects the screws from contact with the metallic humeral head prosthesis. Another approach of the development is a reduction of the resorption of the augmentation by targeted mechanical stimulation of the tissue. The aim should be to achieve significantly improved conditions for the implantation of a new glenoid component at the end of the healing phase of the augmentation material in comparison to the current standard method. The development of the protective prosthesis was carried out according to specific needs and includes the collection of requirements and boundary conditions, the design and technical detailing of the implant, the verification of the development results as well as the validation of the design. For the verification, FEM simulations (Finite Element Analysis) were performed to estimate the mechanical stability in advance. Mechanical tests to confirm the stability and abrasion behavior have been carried out and confirm the suitability of the protective implant. The result of the present work is the detailed technical design of two variants of a glenoid protective prosthesis “GlenoProtect” for use in revision procedures on shoulder joints—with large-volume defects on the glenoid—treated by arthroplasty and the necessity of augmenting the glenoid, including a description of the surgical procedure for implantation.

Processing and properties optimisation of carbon nanofibre-reinforced magnesium composites for biomedical applications

In the last decade, magnesium alloys have been considered as absorbable metals for biomedical applications, while some have reached their clinical use as temporary bone implants. However, their widespread use is still limited by its strength and degradability. One way of improvement can be done by reinforcing magnesium alloys with carbon nanofibres to form composites. This work aims at developing carbon nanofibre-reinforced magnesium-zinc (Mg–Zn/CNF) composites with optimum strength and degradability while ensuring their biocompatibility. A response surface method was used to determine their optimum process parameters (composition, compaction pressure, and sintering temperature), and analyse the resulting properties (elastic modulus, hardness, weight loss, and cytocompatibility). Results showed that the optimal parameters were reached at 1.8% of CNF, 425 MPa of compaction pressure, and 500 °C of sintering temperature, whereby it gave an elastic modulus of 5 GPa, hardness of 60 Hv, and a weight loss of 51% after three days immersion in PBS. The composites exhibited a hydrophobic surface that controlled the liberation of Mg2+ and Zn2+ ions, leading to more than 70% osteoblast cells viability up to seven days of incubation. This study can also serve as a starting point for future researchers interested in finding methods to fabricate Mg–Zn/CNF composites with high mechanical characteristics, corrosion resistance, and biocompatibility.

Long-term antimicrobial effect of polylactide-based composites suitable for biomedical use

This work deals with the preparation and characterization of antimicrobial polymeric composite materials based on polylactide, which is currently widely investigated to produce temporary implants. Polylactide was blended with antimicrobial fillers: silver, hexadecylpyridinium or hexadecyltrimethylammonium bromides anchored on vermiculite or graphene oxide matrices in an amount of 1% wt. The prepared samples were characterized by conventional methods, further they were exposed to degradation tests in physiological saline conditions and characterized for their antimicrobial properties using common pathogen microorganisms. It has been proven that the prepared polylactide composites change their antimicrobial effects after being in physiological saline of pH 7 and 9 for 0–6 months. The weight of the composites changed by about 10%, and antimicrobial properties were growing over time. The effectiveness of the composites was confirmed for 6 months at minimum. Therefore, they are suitable for the preparation of temporary stents, catheters or implants suitable for fracture fixation.

Biodegradable Bone Implants as a New Hope to Reduce Device-Associated Infections-A Systematic Review.

Bone fractures often require fixation devices that frequently need to be surgically removed. These temporary implants and procedures leave the patient more prone to developing medical device-associated infections, and osteomyelitis associated with trauma is a challenging complication for orthopedists. In recent years, biodegradable materials have gained great importance as temporary medical implant devices, avoiding removal surgery. The purpose of this systematic review was to revise the literature regarding the use of biodegradable bone implants in fracture healing and its impact on the reduction of implant-associated infections. The systematic review followed the PRISMA guidelines and was conducted by searching published studies regarding the in vivo use of biodegradable bone fixation implants and its antibacterial activity. From a total of 667 references, 23 studies were included based on inclusion and exclusion criteria. Biodegradable orthopedic implants of Mg-Cu, Mg-Zn, and Zn-Ag have shown antibacterial activity, especially in reducing infection burden by MRSA strains in vivo osteomyelitis models. Their ability to prevent and tackle implant-associated infections and to gradually degrade inside the body reduces the need for a second surgery for implant removal, with expectable gains regarding patients’ comfort. Further in vivo studies are mandatory to evaluate the efficiency of these antibacterial biodegradable materials.

Outcomes of two circular external fixation systems in the definitive treatment of acute tibial fracture related infections

IntroductionAcute tibial fracture-related infection (FRI) is one of the most feared and challenging complications after a tibial fracture. The most appropriate treatment in this scenario is far from a resolved topic. Circular external fixators (CEFs) offer multiplanar control and minimize soft tissue injury using temporary implants far from the infected area. This study aimed to investigate the outcomes of two different types of CEFs (Ilizarov and hexapod) in the treatment of a series of acute tibial FRIs. Material and MethodsA retrospective study at two specialized limb reconstruction centres identified all patients with an acute tibial FRI (≤4 weeks after index procedure) definitively treated with a CEF from January 2015 to December 2020. Primary outcomes: fracture healing and infection eradication rate with a minimum FU of 12 months after frame removal. Secondary outcomes: to investigate the differences between the two types of circular frames regarding final post-treatment deformity magnitude. ResultsWe included 31 patients with acute tibial FRIs: 18 treated with hexapod-type and 13 with Ilizarov-type CEFs. Average age was 45.5±16.56 years. Fracture healing and infection eradication were achieved in all patients (31/31) after a mean follow-up of 24.7 months (range 12.1-55.3). Patients treated with an Ilizarov-type fixator presented shorter time to fracture union (5.5±2.2 months vs. 9.2±6.0 months; p-value 0.021) and shorter duration of external fixation (p-value 0.001). Regarding residual post-treatment deformity, the hexapod system presented significantly less residual coronal translation deformity (p-value 0.034) and better callus quality. Fixator-related complications were similar when comparing the two groups. No significant differences were seen in pain (p-value 0.25), RTW rate (35% vs. 45%; p-value 0.7) or functionality (p-value 0.4). ConclusionsDefinitive circular external fixation is an excellent treatment for acute tibial FRI. Both Ilizarov and hexapod systems offer a very high rate of fracture healing and infection eradication. Although both presented very low radiological post-operative residual deformity, the hexapod system showed less residual coronal translation deformity and better callus quality.

Precipitation in lean Mg–Zn–Ca alloys

While lean Mg–Zn–Ca alloys are promising materials for temporary implants, questions remain on the impact of Zn and Ca on the microstructure. In this context, the precipitation of Zn and Ca in Mg-1.5Zn-0.25Ca (in wt.%), initially extruded at 330°C, towards Mg–Ca binary precipitates or Ca–Mg–Zn ternary precipitates was probed in a multiscale correlative approach using atom probe tomography (APT) and analytical transmission electron microscopy (TEM). Particular focus was set on the ternary precipitate phase whose structure is debated. In the as-extruded material, the binary precipitates are made of hexagonal C14 Mg2Ca containing up to about 3 at.% of Zn. The ternary ones are based on the hexagonal Ca2Mg5Zn5 prototype structure with a composition close to Ca3Mg11Zn4, as deduced from atomically resolved EDS mapping and scanning TEM imaging, supported by simulations. The precipitation sequence was scrutinized upon linear heating from room temperature to 375°C, starting from the solutionized material. Three exothermic differential scanning calorimetry (DSC) peaks were observed, at respectively 125, 250 and 320°C. Samples were taken after the peak decays, at respectively 205, 260 and 375°C for structural analysis. At 205°C, APT analysis revealed Ca-rich, Zn-rich and Zn‒Ca-rich clusters of about 3 nm in size and with a number density of 5.7 × 1023 m−3. At 260°C, APT and TEM showed mono-layered Zn‒Ca-rich Guinier‒Preston (GP) zones of about 8 nm in size and with a number density of 1.3 × 1023 m−3. At 375°C, larger and highly coherent elongated precipitates were found, with a size of about 50 nm. They occur as binary Mg–Ca precipitates or ternary Ca2Mg6Zn3 precipitates, as deduced from scanning TEM-based energy dispersive X-ray spectroscopy (EDS) and nanodiffraction in TEM. Here, the binary precipitates outnumber the ternary ones, while in the as-extruded material the ternary precipitates outnumber the binary ones, which corresponds well to the calculated phase diagram. We correlated the microstructure to hardness probed by Vickers testing. The largest hardening relates to the end of the 125°C DSC peak and thus to GP zones, which outperform the hardening induced by the nanometer-sized clusters and the larger intermetallic particles. The complexity of the precipitation sequence in lean Mg–Zn–Ca alloys is discussed.