Biodegradable Magnesium-based Implants Research Articles

In Vivo Analysis of a Biodegradable Magnesium Alloy Implant in an Animal Model Using Near-Infrared Spectroscopy

Biodegradable magnesium-based implants offer mechanical properties similar to natural bone, making them advantageous over nonbiodegradable metallic implants. However, monitoring the interaction between magnesium and tissue over time without interference is difficult. A noninvasive method, optical near-infrared spectroscopy, can be used to monitor tissue's functional and structural properties. In this paper, we collected optical data from an in vitro cell culture medium and in vivo studies using a specialized optical probe. Spectroscopic data were acquired over two weeks to study the combined effect of biodegradable Mg-based implant disks on the cell culture medium in vivo. Principal component analysis (PCA) was used for data analysis. In the in vivo study, we evaluated the feasibility of using the near-infrared (NIR) spectra to understand physiological events in response to magnesium alloy implantation at specific time points (Day 0, 3, 7, and 14) after surgery. Our results show that the optical probe can detect variations in vivo from biological tissues of rats with biodegradable magnesium alloy "WE43" implants, and the analysis identified a trend in the optical data over two weeks. The primary challenge of in vivo data analysis is the complexity of the implant interaction near the interface with the biological medium.

In Vitro Electrochemical Corrosion Assessment of Magnesium Nanocomposites Reinforced with Samarium(III) Oxide and Silicon Dioxide Nanoparticles

Recent research on biodegradable magnesium-based implants has been focusing on increasing their mechanical strength and controlling their corrosion rate. One promising approach to significantly improve the mechanical properties of magnesium is the addition of nanoparticles to the magnesium matrix. However, there is limited research on the corrosion behavior of these new magnesium nanocomposites. In this study, the electrochemical corrosion characteristics of this new class of biomaterials are investigated. Two magnesium nanocomposites reinforced with nanoparticles (0.5, 1.0, and 1.5 Vol%) of samarium oxide (Sm2O3), and silicon dioxide (SiO2), were fabricated and tested. Corrosion behavior was assessed in comparison with high-purity magnesium samples as the control group. The addition of the nanoparticles to the magnesium matrix strengthened the materials, which was represented in an increase in the microhardness. However, the fabricated nanocomposite samples exhibited a slightly reduced corrosion resistance compared to the high-purity magnesium control due to the differences in the purity level and fabrication methods. Both nanocomposites showed the highest corrosion resistance, represented in the slowest corrosion rates, at the 1.0 Vol% content. Hence, the developed nanocomposites are still promising candidates as biodegradable materials for bone-fixation application owing to their superior mechanical properties and acceptable corrosion characteristics.

Evaluating metallic artefact of biodegradable magnesium-based implants in magnetic resonance imaging

Magnesium (Mg) implants have shown to cause image artefacts or distortions in magnetic resonance imaging (MRI). Yet, there is a lack of information on how the degradation of Mg-based implants influences the image quality of MRI examinations. In this study, Mg-based implants are analysed in vitro, ex vivo, and in the clinical setting for various magnetic field strengths with the aim to quantify metallic artefact behaviour. In vitro corroded Mg-based screws and a titanium (Ti) equivalent were imaged according to the ASTM F2119. Mg-based and Ti pins were also implanted into rat femurs for different time points and scanned to provide insights on the influence of soft and hard tissue on metallic artefact. Additionally, MRI data of patients with scaphoid fractures treated with CE-approved Mg-based compression screws (MAGNEZIX®) were analysed at various time points post-surgery. The artefact production of the Mg-based material decreased as implant material degraded in all settings. The worst-case imaging scenario was determined to be when the imaging plane was selected to be perpendicular to the implant axis. Moreover, the Mg-based implant outperformed the Ti equivalent in all experiments by producing lower metallic artefact (p < 0.05). This investigation demonstrates that Mg-based implants generate significantly lower metallic distortion in MRI when compared to Ti. Our positive findings suggest and support further research into the application of Mg-based implants including post-operative care facilitated by MRI monitoring of degradation kinetics and bone/tissue healing processes.

Advances of biodegradable magnesium-based implants for orthopaedics

Advances of biodegradable magnesium-based implants for orthopaedics

Effect of Galvanic Corrosion on the Degradability of Biomedical Magnesium

With recent progress in clinical trials and scale-up applications of biodegradable magnesium-based implants, the scenarios of transplanting biodegradable Mg with other non-degradable metals may occur inevitably. Galvanic corrosion appears between two metallic implants with different electrochemical potentials and leads to accelerated degradation. However, a quantitative measurement on the galvanic corrosion of Mg in contact with other metallic implants has not been conducted. Here we study the corrosion behaviors and mechanical attenuation of high purity magnesium (Mg)in contact with stainless steel (316L), pure titanium (TA2), and magnesium alloy (AZ91) respectively to form different galvanic couples in simulated body fluids. The results show that all of these three heterogeneous metal pairs accelerate the degradation of high purity Mg to different degrees, yielding declined tensile strength and mechanical failure after 4 days of immersion. Our observations alert the potential risk of co-implanting different metallic devices in clinical trials.

Multi-scale mechanical and morphological characterisation of sintered porous magnesium-based scaffolds for bone regeneration in critical-sized defects

Magnesium (Mg) and its alloys are very promising degradable, osteoconductive and osteopromotive materials to be used as regenerative treatment for critical-sized bone defects. Under load-bearing conditions, Mg alloys must display sufficient morphological and mechanical resemblance to the native bone they are meant to replace to provide adequate support and enable initial bone bridging. In this study, unique highly open-porous Mg-based scaffolds were mechanically and morphologically characterised at different scales. In situ X-ray computed tomography (XCT) mechanics, digital volume correlation (DVC), electron microscopy and nanoindentation were combined to assess the influence of material properties on the apparent (macro) mechanics of the scaffold. The results showed that Mg exhibited a higher connected structure (38.4mm−3 and 6.2mm−3 for Mg and trabecular bone (Tb), respectively) and smaller spacing (245µm and 629µm for Mg and Tb, respectively) while keeping an overall appropriate porosity of 55% in the range of trabecular bone (30-80%). This fully connected and highly porous structure promoted lower local strain compared to the trabecular bone structure at material level (i.e. -22067 ± 8409µε and -40120 ± 18364µε at 6% compression for Mg and trabecular bone, respectively) and highly ductile mechanical behaviour at apparent level preventing premature scaffold failure. Furthermore, the Mg scaffolds exceeded the physiological strain of bone tissue generated in daily activities such as walking or running (500-2000µε) by one order of magnitude. The yield stress was also found to be close to trabecular bone (2.06MPa and 6.67MPa for Mg and Tb, respectively). Based on this evidence, the study highlights the overall biomechanical suitability of an innovative Mg-based scaffold design to be used as a treatment for bone critical-sized defects. Statement of significanceBone regeneration remains a challenging field of research where different materials and solutions are investigated. Among the variety of treatments, biodegradable magnesium-based implants represent a very promising possibility. The novelty of this study is based on the characterisation of innovative magnesium-based implants whose structure and manufacturing have been optimised to enable the preservation of mechanical integrity and resemble bone microarchitecture. It is also based on a multi-scale approach by coupling high-resolution X-ray computed tomography (XCT), with in situ mechanics, digital volume correlation (DVC) as well as nano-indentation and electron-based microscopy imaging to define how degradable porous Mg-based implants fulfil morphological and mechanical requirements to be used as critical bone defects regeneration treatment.

Safety and performance of biodegradable magnesium-based implants in children and adolescents

AimsBiodegradable magnesium-based alloy implants represent a promising option in orthopedic surgery, as the clinical outcomes have been reported to be comparable to those of titanium implants and no surgical interventions are required for removal. To date, little is known about the results of the use of these implants in children and adolescents. Therefore, the aim of the present study was to analyze the safety and performance of these implants in children and adolescents. Patients and MethodsEighty-nine patients treated with magnesium-based implants for fracture stabilization, osteotomy and osteochondral refixation were analyzed; 38 were treated by osteosynthesis; 18, osteotomy; and 33, osteochondral refixation. The mean follow-up duration was 8.2 months (range, 1.5–30 months). Clinical and radiographical follow-up examinations were performed at 4–8 weeks and 3–6 months, respectively, to evaluate implant performance and osseous consolidation. ResultsClinical outcomes were rated as good to very good in all patients. Radiolucent zones were apparent after surgery in all patients but were noted to decrease in size during the follow-up period. Revision surgery was necessary in 1 of 89 patients who had a highly unstable osteochondritis dissecans lesion of the knee. None of the magnesium-based implants required surgical removal. ConclusionMagnesium-based implants in children and adolescents results in good clinical outcomes when used for fracture stabilization, osteotomy and osteochondral defect refixation. Future studies are needed to further analyze the significance of the transient appearance and temporal development of radiolucent zones in the growing skeleton as well as the long-term performance of these implants.

Biodegradable magnesium screws in elbow fracture fixation: Clinical case series

Biodegradable magnesium-based implants are innovative alternatives that potentially eliminate the need for implant removal. Recent studies have demonstrated the osteogenic properties and bacterial inhibition potentials of magnesium screws. We reported a clinical series of three elbow fracture cases, where magnesium screws were used in the treatment of one radial head and two capitellum fractures. Postoperative clinical courses were uneventful, and fracture healing occurred within 3 months. In all cases, radiolucencies were observed around implants especially in the screw head region at 2 months post-operation, but disappeared with consolidation at 1 year post-operation. All patients achieved near normal range of motion, minimal symptoms and good functional outcomes. No complication such as failure of fixation, loss of reduction, malunion or infection was seen. No implant revision or removal was necessary. Magnesium bioabsorbable screws are shown to be a viable option for these fractures.

Biodegradable Magnesium-Based Implants in Orthopedics-A General Review and Perspectives.

Biodegradable Mg‐based metals may be promising orthopedic implants for treating challenging bone diseases, attributed to their desirable mechanical and osteopromotive properties. This Review summarizes the current status and future research trends for Mg‐based orthopedic implants. First, the properties between Mg‐based implants and traditional orthopedic implants are compared on the following aspects: in vitro and in vivo degradation mechanisms of Mg‐based implants, peri‐implant bone responses, the fate of the degradation products, and the cellular and molecular mechanisms underlying the beneficial effects of Mg ions on osteogenesis. Then, the preclinical studies conducted at the low weight bearing sites of animals are introduced. The innovative strategies (for example, via designing Mg‐containing hybrid systems) are discussed to address the limitations of Mg‐based metals prior to their clinical applications at weight‐bearing sites. Finally, the available clinical studies are summarized and the challenges and perspectives of Mg‐based orthopedic implants are discussed. Taken together, the progress made on the development of Mg‐based implants in basic, translational, and clinical research has laid down a foundation for developing a new era in the treatment of challenging and prevalent bone diseases.

Mechanical properties and in vivo biodegradability of Mg–Zr–Y–Nd–La magnesium alloy produced by a combined severe plastic deformation

Permanent implants are going to be replaced by the implementation of biodegradable magnesium-based implants in fixation of internal bone fractures because of many concerns associated with conventional implants. However, biodegradable magnesium-based biomaterials exhibit higher biodegradation rate and low mechanical properties which are the main challenges. This work aims to almost overcome both disadvantageous by grain refining of a WE43 magnesium alloy containing 93.04 wt% Mg, 4.12 wt% Y, 2.15 wt% Nd, 0.43 wt% Zr, and 0.26 wt% La. In this study, the consequences of combined severe plastic deformation (SPD) on the mechanical properties, microstructure, and in vivo degradation behavior of WE43 magnesium alloy were investigated. To do so, WE43 magnesium alloy was chosen and processed through multi-pass equal channel angular pressing (ECAP) at 330 °C for up to four passes followed by an extrusion process. The results showed that higher strength and hardness with minimum ductility less was obtained in the sample processed via two-pass ECAP followed by extrusion. In vivo biodegradation experiments showed higher degradation rate for the unprocessed coarse-grained (CG) WE43 sample. The two-pass ECAP and extruded sample with ultrafine-grained (UFG) structure exhibited the lowest in vivo biodegradation rate besides appropriate mechanical properties. It may be concluded that the WE43 magnesium alloy processed via two-pass ECAP and extrusion could be a very promising candidate for biodegradable implants from both mechanical and biocorrosion viewpoints.

Development of magnesium implants by application of conjoint-based quality function deployment.

Biodegradable magnesium-based implants are the subject of a great deal of research for different orthopedic and vascular applications. The targeted design and properties depend on the specific medical function and location in the body. Development of the biomaterial requires a comprehensive understanding of the biological interaction between the implant and the host tissue, as well as of the behavior in the physiological environment in vivo. Research into and the development of innovative magnesium implants entails interdisciplinary research efforts and communication between materials science, bioscience, and medical experts. The present study provides a transparent planning and communication tool for market-oriented implant development processes. The objective was to identify medical needs at an early stage of the development process and to quantify the importance of the engineering characteristics of different research fields that cater to specific implant requirements. The method is demonstrated by the performance of a survey-based conjoint analysis, which was integrated into a quality function deployment approach. Twenty-seven medical professionals and 29 biomaterial scientists assessed the importance of identified medical requirements, whereby the control of mechanical integrity and degradation along with nontoxicity and nonimmunogenicity showed the highest number of preferences. The evaluation of implant options by 31 experts indicated that the engineering characteristic with the highest importance was the condition and sterilization of the surface. These values can be used to set priorities in strategic decisions. Research trials can be aligned to medical preferences, ensuring high product quality and an effective development process. This is the first paper to report on the application of conjoint-based quality function deployment in biomaterial research.

Comparison of SCAphoid fracture osteosynthesis by MAGnesium-based headless Herbert screws with titanium Herbert screws: protocol for the randomized controlled SCAMAG clinical trial

BackgroundScaphoid fractures are the most common carpal fractures. They often need to be treated by surgery, where the use of a compression screw is the globally accepted gold standard. Surgeons may choose between different implant materials including titanium alloys, which remain in the body or are removed after healing. An alternative are biodegradable magnesium-based implants. Properties of magnesium alloys include high stability, osteoconductivity, potential reduction of infections and few artifacts in magnetic resonance imaging (MRI). The aim of this trial is to demonstrate non-inferiority of magnesium-based compression screws compared with titanium Herbert screws for scaphoid fractures.MethodsThe trial is designed as a multicenter, blinded observer, randomized controlled parallel two-group post market trial. Approximately 190 patients will be randomized (1:1) with stratification by center either to titanium or magnesium-based compression screws. Follow-up is 1 year per patient. Surgical procedures and aftercare will be performed according to the German treatment guideline for scaphoid fractures. The first primary endpoint is the patient-rated wrist evaluation (PRWE) score after 6 months. The second primary endpoint is a composite safety endpoint including bone union until 6 months, no adverse device effect (ADE) during surgery or wound healing and no serious ADE or reoperation within 1 year. The third primary endpoint is the difference in change MRI artifacts over time. Non-inferiority will be investigated for primary endpoints 1 (t-test confidence interval) and 2 (Wilson’s score interval) using both the full analysis set (FAS) and the per protocol population at the one-sided 2.5% test-level. Superiority of magnesium over titanium screws will be established using the FAS at the two-sided 5% test-level (Welch test) only if non-inferiority has been established for both primary endpoints. Secondary endpoints include quality of life.DiscussionThis study will inform care providers whether biodegradable magnesium-based implants are non-inferior to standard titanium Herbert screws for the treatment of scaphoid fractures in terms of wrist function and safety. Furthermore, superiority of magnesium-based implants may be demonstrated using MRI, which is used as surrogate endpoint for screw degradation.Trial registrationDRKS, DRKS00013368. Registered Dec 04, 2017.

Elemental mapping of biodegradable magnesium-based implants in bone and soft tissue by means of μ X-ray fluorescence analysis

Besides the biocompatibility and potential support of bone-healing, homogeneous degradation and the uniform distribution of degradation products are key factors for a successful medical application of magnesium (Mg)-based materials as biodegradable implants in orthopedic therapies.

Dual modulation of bone formation and resorption with zoledronic acid-loaded biodegradable magnesium alloy implants improves osteoporotic fracture healing: An in vitro and in vivo study.

Management of osteoporotic fracture has posed a major challenge in orthopedics, as the imbalance between diminished osteogenesis and excessive bone remodeling often leads to delayed and compromised fracture repair. Among various efforts expended on augmenting osteoporotic fracture healing, herein we reported a new strategy by engineering and utilizing a biodegradable magnesium-based implant integrated with local drug delivery, specifically, zoledronic acid (ZA)-loaded polylactic acid/brushite bilayer coating on a biodegradable Mg-Nd-Zn-Zr alloy (denoted as Mg/ZA/CaP), aiming to combine the favorable properties of Mg and zoledronic acid for simultaneous modulation of bone formation and bone resorption. In vitro and in vivo studies demonstrated its superior treatment efficacy along with adequate degradation. It stimulated new bone formation while suppressing remodeling, ascribed to the local release of magnesium degradation products and zoledronic acid. To our knowledge, the enhanced fracture repair capability of Mg-based implants was for the first time demonstrated in an osteoporotic fracture animal model. This innovative biodegradable Mg-based orthopedic implant presents great potential as a superior alternative to current internal fixation devices for treating osteoporotic fracture.

Differential apoptotic response of MC3T3-E1 pre-osteoblasts to biodegradable magnesium alloys in an in vitro direct culture model

The biodegradable magnesium-based implants have been widely utilized in medical orthopedic applications in recent years. We have recently shown that direct culture on Pure Mg and Mg2Ag alloys lead to a progressive differentiation impairment of MC3T3-E1 pre-osteoblasts. In this study, we aimed to analyze the apoptotic reaction of MC3T3-E1 cells in response to the direct culture on Pure Mg, Mg2Ag and Extreme High Pure Mg (XHP Mg) alloy samples. Our results demonstrated that long-term culturing of MC3T3-E1 cells on Pure Mg and Mg2Ag alloys induce time-dependent expression of active caspase-3 (active casp-3) and cleaved PARP-1 (cl. PARP-1), the hallmark of apoptosis reactions concomitant with a significant increase in the number of dead cells. However, direct culture on XHP Mg material results in a lower number of dead cells in comparison to Pure Mg and Mg2Ag alloys. Furthermore, XHP Mg materials influence expression of apoptotic markers in a process resembles that of observed in osteogenic condition apparently indicative of MC3T3-E1 osteodifferentiation. This study indicates that Mg alloy samples mediated differential apoptotic reactions of MC3T3-E1 cells can be ascribed to factors such as distinct topography and hydrophobicity features of Mg material surfaces, contrasting nature/composition of corrosion products as well as different impurities of these materials. Therefore, initial Mg alloys surface preparation, controlling the growth and composition of corrosion products and Mg alloys purity enhancement are necessary steps towards optimizing the Mg alloys usage in medical orthopedic applications.Graphical

In vitro degradation behavior and cytocompatibility of biodegradable AZ31 alloy with PEO/HT composite coating

Biodegradable magnesium-based implants have attracted much attention recently in orthopedic applications because of their good mechanical properties and biocompatibility. However, their rapid degradation in vivo will not only reduce their mechanical strength, but also induce some side effects, such as local alkalization and gas cavity, which may lead to a failure of the implant. In this work, a hydroxyapatite (HA) layer was prepared on plasma electrolytic oxidization (PEO) coating by hydrothermal treatment (HT) to fabricate a PEO/HT composite coating on biodegradable AZ31 alloy. The in vitro degradation behaviors of all samples were evaluated in simulated body fluid (SBF) and their surface cytocompatibility was also investigated by evaluating the adhesion and proliferation of osteoblast cells (MC3T3-E1). The results showed that the HA layer consisted of a dense inner layer and a needle-like outer layer, which successfully sealed the PEO coating. The in vitro degradation tests showed that the PEO/HT composite coating improved the corrosion resistance of AZ31 alloy in SBF, presenting nearly no severe local alkalization and hydrogen evolution. The lasting corrosion resistance of the PEO/HT composite coating may attribute to the new hydroxyapatite formation during the degradation process. Moreover, compared with AZ31 alloy and PEO coating, PEO/HT composite coating was more suitable for cells adhesion and proliferation, indicating improved surface cytocompatibility. The results show that the PEO/HT composite coating is promising as protective coating on biodegradable magnesium-based implants to enhance their corrosion resistance as well as improve their surface cytocompatibility for orthopedic applications.

In vivo study of a biodegradable orthopedic screw (MgYREZr-alloy) in a rabbit model for up to 12 months

Biodegradable magnesium-based implants are currently being developed for use in orthopedic applications. The aim of this study was to investigate the acute, subacute, and chronic local effects on bone tissue as well as the systemic reactions to a magnesium-based (MgYREZr-alloy) screw containing rare earth elements. The upper part of the screw was implanted into the marrow cavity of the left femora of 15 adult rabbits (New Zealand White), and animals were euthanized 1 week, 12 weeks, and 52 weeks postoperatively. Blood samples were analyzed at set times, and radiographic examinations were performed to evaluate gas formation. There were no significant increased changes in blood values compared to normal levels. Histological examination revealed moderate bone formation with direct implant contact without a fibrous capsule. Histopathological evaluation of lung, liver, intestine, kidneys, pancreas, and spleen tissue samples showed no abnormalities. In summary, our data indicate that these magnesium-based screws containing rare earth elements have good biocompatibility and osteoconductivity without acute, subacute, or chronic toxicity.