Accumulated knowledge

Background: For the treatment of hallux valgus commonly distal metatarsal osteotomies are performed. Persistent problems due to the hardware and the necessity of hardware removal has led to the development of absorbable implants. To overcome the limitations of formerly used materials for biodegradable implants, recently magnesium has been introduced as a novel implant material. This is the first study showing mid-term clinical and radiological (MRI) data after using magnesium implants for fixation of distal metatarsal osteotomies.

Material and methods: 26 patients with symptomatic hallux valgus were included in the study. They were randomly selected to be treated with a magnesium or standard titanium screw for fixation of a modified distal metatarsal osteotomy. The patients had a standardized clinical follow up and MRI investigation 3 years' post-surgery. The clinical tests included the range of motion of the MTP 1, the AOFAS, FAAM and SF-36 scores. Further on the pain was evaluated on a VAS.

Results: Eight patients of the magnesium group and 6 of the titanium group had a full clinical and MRI follow up 3 years postoperatively. One patient was lost to follow-up. All other patients could be interviewed, but denied full study participation. There was a significant improvement for all tested clinical scores (AOFAS, SF-36, FAAM, Pain-NRS) from pre-to postoperative investigation, but no statistically relevant difference between the groups. Magnesium implants showed significantly less artifacts in the MRI, no implant related cysts were found and the implant was under degradation three years postoperatively.

Conclusion: In this study, bioabsorbable magnesium implants showed comparable clinical results to titanium standard implants 3 years after distal modified metatarsal osteotomy and were more suitable for radiologic analysis.

MAGNEZIX^® CS (Syntellix AG, Hanover, Germany) is a bioabsorbable compression screw made of a magnesium alloy (MgYREZr). Currently there are only two clinical studies reporting on a limited number of elective patients who received this screw in a hallux valgus operation. We applied MAGNEZIX^® CS for fixation of distal fibular fracture in a trauma patient who had sustained a bimalleolar fracture type AO 44-B2.3. Clinical course was uneventful, fracture healing occurred within three months. Follow-up X-rays showed a radiolucent area around the implant for some months, yet this radiolucent area had disappeared in the 17-months follow-up X-ray.

Background: Magnesium alloys have recently been rediscovered as biodegradable implants in musculoskeletal surgery. This study is an ex-vivo trial to evaluate the imaging characteristics of magnesium implants in different imaging modalities as compared to conventional metallic implants.

Methods: A CE-approved magnesium Herbert screw (MAGNEZIX^®) and a titanium screw of the same dimensions (3.2x20 mm) were imaged using different modalities: digital radiography (DX), multidetector computed tomography (MDCT), high resolution flat panel CT (FPCT) and magnetic resonance imaging (MRI). The screws were scanned invitro and after implantation in a fresh chicken tibia in order to simulate surrounding bone and soft tissue.The images were quantitatively evaluated with respect to the overall image quality and the extent and intensity of artifacts.

Results: In all modalities, the artifacts generated by the magnesium screw had a lesser extent and were less severe as compared to the titanium screw (mean difference of artifact size of solo scanned screws in DX: 0.7 mm, MDCT: 6.2 mm, FPCT: 5.9 mm and MRI: 4.73 mm; p < 0.05). In MDCT and FPCT multiplanar reformations and 3D reconstructions were superior as compared with the titanium screw and the metal-bone interface after implanting the screws in chicken cadavers was more clearly depicted. While the artifacts of the titanium screw could be effectively reduced using metal-artifact reduction sequences in MRI (WARP, mean reduction of 2.5 mm, p < 0.05), there was no significant difference for the magnesium screw.

Conclusions: Magnesium implants generate significantly less artifacts in common imaging modalities (DX, MDCT, FPCT and MRI) as compared with conventional titanium implants and therefore may facilitate post-operative follow-up.

The clinical application of degradable orthopedic magnesium implants is a tangible vision in medical science. This interdisciplinary review discusses many different aspects of magnesium alloys comprising the manufacturing process and the latest research. We present the challenges of the manufacturing process of magnesium implants with the risk of contamination with impurities and its effect on corrosion. Furthermore, this paper provides a summary of the current examination methods used in in vitro and in vivo research of magnesium alloys. The influence of various parameters (most importantly the effect of the corrosive media) in in vitro studies and an overview about the current in vivo research is given.

Purpose: Nondegradable steel-and titanium-based implants are commonly used in orthopedic surgery. Although they provide maximal stability, they are also associated with interference on imaging modalities, may induce stress shielding, and additional explantation procedures may be necessary. Alternatively, degradable polymer implants are mechanically weaker and induce foreign body reactions. Degradable magnesium-based stents are currently being investigated in clinical trials for use in cardiovascular medicine. The magnesium alloy MgYREZr demonstrates good biocompatibility and osteoconductive properties. The aim of this prospective, randomized, clinical pilot trial was to determine if magnesium-based MgYREZr screws are equivalent to standard titanium screws for fixation during chevron osteotomy in patients with a mild hallux valgus.

Methods: Patients (n=26) were randomly assigned to undergo osteosynthesis using either titanium or degradable magnesium based implants of the same design. The 6 month follow-up period included clinical, laboratory, and radiographic assessments.

Results: No significant differences were found in terms of the American Orthopaedic Foot and Ankle Society (AOFAS) score for hallux, visual analog scale for pain assessment, or range of motion (ROM) of the first metatarsophalangeal joint (MTPJ). No foreign body reactions, osteolysis, or systemic inflammatory reactions were detected. The groups were not significantly different in terms of radiographic or laboratory results.

Conclusion: The radiographic and clinical results of this prospective controlled study demonstrate that degradable magnesium-based screws are equivalent to titanium screws for the treatment of mild hallux valgus deformities.

Degradable magnesium alloys are promising biomaterials for orthopedic applications. The aim of this study was to evaluate the potential effects on both the synovial membrane (synovialis) and the synovial fluid (synovia) of the degradation products of a MgYREZr-pin implanted in the intercondylar femoral notch in a rabbit model. Thirty-six animals were randomized into two groups (MgYREZr or Ti6Al4V alloy) of 18 animals each. Each group was then divided into three subgroups with implantation periods of 1, 4, and 12 weeks, with six animals in each subgroup. The initial inflammatory reaction caused by the surgical trauma declined after 12 weeks of implantation, and elucidated a progressive recovery of the synovial membrane. Compared with control Ti6Al4V pins, there were no significant differences between the groups. However, after 12 weeks, recovery of the synovial membrane was more advanced in the titanium group, in which 92% showed no signs of synovitis, than in the magnesium group. A cytotoxicity test with L929 cells and human osteoblasts (HOB) was also conducted, according to EN ISO 10993-5/12, and no toxic leachable products were observed after 24 h of incubation. In conclusion, the MgYREZr alloy seems to be a suitable material for intra-articular degradable implants.

Aims and objectives: Magnesium (Mg) alloys have recently been rediscovered as biodegradable implants in musculoskeletal surgery [1,2]. A major advantage of Mg-based biomaterials is their property to produce only little artifacts in the common imaging modalities [3]. However, there is very limited experience with imaging of Mg-based orthopedic materials. This study is an ex-vivo trial to evaluate the imaging characteristics of Mg implants in different imaging modalities as compared to conventional titanium (Ti) implants.

Methods and materials: A CE-approved Mg Herbert screw (MAGNEZIX®) and a Ti screw of the same dimensions (3.2x20 mm) were imaged using different modalities: digital radiography (DX), multidetector computed tomography (MDCT), high resolution flat panel CT (FPCT) and magnetic resonance imaging (MRI). The screws were scanned native and after implantation in a fresh chicken tibia in order to simulate surrounding bone and soft tissue. Different scanning protocols and screw positions with respect to the longitudinal scanner axis were compared. The images were quantitatively evaluated with respect to the overall image quality and the extent and intensity of artifacts. All artifacts were assessed in an axial plane or reconstruction of the screw.

Results: In all modalities, the artifacts generated by the Mg screw had a lesser extent and were less severe as compared to the Ti screw. The mean difference of artifact size of the native screws was in DX: 0.7 mm, MDCT: 6.2 mm, FPCT: 5.9 mm, MRI PD TSE: 2.6 mm and in MRI T1: 4.5 mm with p < 0.005. Fig. 1 illustrates the artifacts in a FPCT scan of a Mg and a Ti screw without any surrounding soft or bony tissue. Moreover it demonstrates the superiority of a 3D reconstruction of the Mg screw in comparison to Ti. [...]

Conlusion: Mg implants generate significantly less artifacts in common imaging modalities as compared with conventional implants and therefore may facilitate post-operative follow-up.

Purpose: Degradable magnesium implants have received increasing interest in recent years. In anterior cruciate ligament reconstruction surgery, the well-known osteoconductive effects of biodegradable magnesium alloys may be useful. The aim of this study was to examine whether interference screws made of MgYREZr have comparable biomechanical properties to commonly used biodegradable screws and whether a different thread on the magnesium screw has an influence on the fixation strength.

Methods: Five magnesium (MgYREZr-alloy) screws were tested per group. Three different groups with variable thread designs (Designs 1, 2, and 3) were produced and compared with the commercially available bioabsorbable Bioacryl rapid polylactic-co-glycolic acid screw Milagro®. In vitro testing was performed in synthetic bone using artificial ligament fixed by an interference screw. The constructs were pretensioned with a constant load of 60 N for 30 s followed by 500 cycles between 60 N and 250 N at 1 Hz. Construct displacements between the 1st and 20th and the 21st and 500th cycles were recorded. After a 30 s break, a maximum load to failure test was performed at 1 mm/s measuring the maximum pull-out force.

Results: The maximum loads to failure of all three types of magnesium interference screws (Design 1: 1,092 ± 133.7 N; Design 2: 1,014 ± 103.3 N; Design 3: 1,001 ± 124 N) were significantly larger than that of the bioabsorbable Milagro® interference screw (786.8 ± 62.5 N) (p < 0.05). However, the greatest maximum load was found with magnesium screw Design 1. Except for a significant difference between Designs 1 and 2, there were no further significant differences among the four groups in displacement after the 20th cycle.

Conclusions: Biomechanical testing showed higher pullout forces for magnesium compared with a commercial polymer screw. Hence, they suggest better stability and are a potential alternative. The thread geometry does not significantly influence the stability provided by the magnesium implants. This study shows the first promising results of a degradable material, which may be a clinical alternative in the future.

By utilising its rapid corrosion reaction and controlling its degradation process through Zn and Mn alloying, purification and anodization, chemically active magnesium can be developed into a biodegradable biocompatible implant material with a specific biodegradation process and tolerable hydrogen evolution rate, which may replace current problematic biodegradable polymers in applications.

Introduction: magnesium alloys represent a novel implant material for the production of resorbable implants. Only a minor amount of experience has been gained to date in the behaviour of these implants in MRT. Visualising the degradation process in humans via MRT has so far not taken place. 

Materials and methods: four patients who had received implants of an absorbable magnesium (Mg) screw after distal metatarsal-I-osteotomy, were subsequently investigated using MRT. The investigations took place after 3, 6, and 36 months.

Findings: in vivo investigations revealed that fewer susceptibility artefacts when using magnesium implants were found compared to standard implants made of steel or titanium alloys. Bone healing pursued without any delay. The degradation process of the implant could be documented. This revealed an accompanying bone oedema, but this did not correlate at all with the clinical and subjective findings. 

Discussion: this first study revealed the degradation of the Mg implants as well as a medulla oedema Additional studies and comparison with a collective using standard implants is necessary to be able to reach a final conclusion.

This is the first larger study analyzing the use of magnesium-based screws for fixation of modified Chevron osteotomies in hallux valgus surgery. 44 patients (45 feet) were included in this prospective study. A modified Chevron osteotomy was performed on every patient and a magnesium screw used for fixation. The mean clinical follow up was 21.4 weeks. The mean age of the patients was 45.5 years. 40 patients could be provided with the implant, in 4 patients the surgeon decided to change to a standard metallic implant. The AOFAS, FAAM and pain NRS-scale improved markedly. The hallux valgus angle, intermetatarsal angle and sesamoid position improved significantly. Seven patients showed dorsal subluxation, rotation or medial shifting of the metatarsal heads within the first three months. One of these patients was revised, in all others the findings were considered clinically not significant or the patients refused revision. This study shows the feasibility of using magnesium screws in Hallux valgus-surgery. Surgeons starting with the use of these implants should be aware of the proper handling of these implants and should know about corrosion effects during healing and its radiographic appearance. 

Abstract

It is difficult to fix fractures of the condylar head of the mandible. Several techniques have been described which show satisfactory outcomes,but stability can be questionable, and some can cause irritation of the soft tissues. We describe a technique and first results of treating suchfractures with resorbable magnesium-based headless bone screws (Magnezix®2.7 mm CS; Syntellix AG, Hanover, Germany).

Background: The use of a resorbable implant can help avoid the need to reoperate to remove metal after operations on the front foot. Magnesium alloys are an innovative material for the production of biodegradable implants. 

Materials and methods: in a prospective clinical study, patients received a biodegradable magnesium implant in our hospital and were prospectively followed up. During the study period from August 2013 to February 2015, 22 patients with distal metatarsal-1-osteotomies by mild to moderate Hallux valgus deformity were treated with a MAGNEZIX®-screw.

Results: one patient suffered from a traumatic dislocation of the osteotomy, all of the others showed safe bony healing after 6 to 12 weeks. Prolonged swelling appeared in one patient. The clinical findings were comparable to published series using steel or titanium implants.

Discussion: biodegradable Mg implants are an alternative for osteosynthesis by distal metatarsal osteotomies. There are currently only short-term to medium-term findings available which means that final assessment requires longer term observation periods and a larger patient collective. 

Abstract

Orthopedic implants containing biodegradable magnesium have been used for fracture repair with considerable efficacy; however, the underlying mechanisms by which these implants improve fracture healing remain elusive. Here we show the formation of abundant new bone at peripheral cortical sites after intramedullary implantation of a pin containing ultrapure magnesium into the intact distal femur in rats. This response was accompanied by substantial increases of neuronal calcitonin gene-related polypeptide-α (CGRP) in both the peripheral cortex of the femur and the ipsilateral dorsal root ganglia (DRG). Surgical removal of the periosteum, capsaicin denervation of sensory nerves or knockdown in vivo of the CGRP-receptor-encoding genes Calcrl or Ramp1substantially reversed the magnesium-induced osteogenesis that we observed in this model. Overexpression of these genes, however, enhanced magnesium-induced osteogenesis. We further found that an elevation of extracellular magnesium induces magnesium transporter 1 (MAGT1)-dependent and transient receptor potential cation channel, subfamily M, member 7 (TRPM7)-dependent magnesium entry, as well as an increase in intracellular adenosine triphosphate (ATP) and the accumulation of terminal synaptic vesicles in isolated rat DRG neurons. In isolated rat periosteum-derived stem cells, CGRP induces CALCRL- and RAMP1-dependent activation of cAMP-responsive element binding protein 1 (CREB1) and SP7 (also known as osterix), and thus enhances osteogenic differentiation of these stem cells. Furthermore, we have developed an innovative, magnesium-containing intramedullary nail that facilitates femur fracture repair in rats with ovariectomy-induced osteoporosis. Taken together, these findings reveal a previously undefined role of magnesium in promoting CGRP-mediated osteogenic differentiation, which suggests the therapeutic potential of this ion in orthopedics.

Degrading metal alloys are a new class of implant materials suitable for bone surgery. The aim of this study was to investigate the degradation mechanism at the bone–implant interface of different degrading magnesium alloys in bone and to determine their effect on the surrounding bone. Sample rods of four different magnesium alloys and a degradable polymer as a control were implanted intramedullary into the femora of guinea pigs. After 6 and 18 weeks, uncalcified sections were generated for histomorphologic analysis. The bone–implant interface was characterized in uncalcified sections by scanning electron microscopy (SEM), element mapping and X-ray diffraction. Results showed that metallic implants made of magnesium alloys degrade in vivo depending on the composition of the alloying elements. While the corrosion layer of all magnesium alloys accumulated with biological calcium phosphates, the corrosion layer was in direct contact with the surrounding bone. The results further showed high mineral apposition rates and an increased bone mass around the magnesium rods, while no bone was induced in the surrounding soft tissue. From the results of this study, there is a strong rationale that in this research model, high magnesium ion concentration could lead to bone cell activation.

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.

The first degradable implant made of a magnesium alloy, a compression screw, was launched to the clinical market in March 2013. Many different complex considerations are required for the marketing authorization of degradable implant materials. This review gives an overview of existing and proposed standards for implant testing for marketing approval. Furthermore, different common in vitro and in vivo testing methods are discussed. In some cases, animal tests are inevitable to investigate the biological safety of a novel medical material. The choice of an appropriate animal model is as important as subsequent histological examination. Further, this review focuses on the results of various mechanical tests to investigate the stability of implants for temporary use. All the above aspects are examined in the context of development and testing of magnesium-based biomaterials and their progress them from bench to bedside. A brief history of the first market launch of a magnesium-based degradable implant is given.

Abstract

The first degradable implant made of a magnesium alloy, a compression screw, was launched to the clinical market in March 2013. Many different complex considerations are required for the marketing authorization of degradable implant materials. This review gives an overview of existing and proposed standards for implant testing for marketing approval. Furthermore, different common in vitro and in vivo testing methods are discussed. In some cases, animal tests are inevitable to investigate the biological safety of a novel medical material. The choice of an appropriate animal model is as important as subsequent histological examination. Furthermore, this review focuses on the results of various mechanical tests to investigate the stability of implants for temporary use. All the above aspects are examined in the context of development and testing of magnesium-based biomaterials and their progress them from bench to bedside. A brief history of the first market launch of a magnesium-based degradable implant is given.

Owing to their mechanical properties, metallic materials present a promising solution in the field of resorbable implants. The magnesium metabolism in humans differs depending on its introduction. The natural, oral administration of magnesium via, for example, food, essentially leads to an intracellular enrichment of Mg2+. In contrast, introducing magnesium-rich substances or implants into the tissue results in a different decomposition behavior. Here, exposing magnesium to artificial body electrolytes resulted in the formation of the following products: magnesium hydroxide, magnesium oxide, and magnesium chloride, as well as calcium and magnesium apatites. Moreover, it can be assumed that Mg2+, OH− ions, and gaseous hydrogen are also present and result from the reaction for magnesium in an aqueous environment. With the aid of physiological metabolic processes, the organism succeeds in either excreting the above mentioned products or integrating them into the natural metabolic process. Only a burst release of these products is to be considered a problem. A multitude of general tissue effects and responses from the Mg's degradation products is considered within this review, which is not targeting specific implant classes. Furthermore, common alloying elements of magnesium and their hazardous potential in vivo are taken into account.

MAGNEZIX^® (Syntellix AG, Hanover, Germany) is a biodegradable magnesium-based alloy (MgYREZr) which is currently used to manufacture bioabsorbable compression screws. To date, there are very few studies reporting on a limited number of elective foot surgeries using this innovative implant. This case report describes the application of this screw for osteochondral fracture fixation at the humeral capitulum next to a loose radial head prosthesis, which was revised at the same time. The clinical course was uneventful. Degradation of the magnesium alloy did not interfere with fracture healing. Showing an excellent clinical result and free range-of-motion, the contour of the implant was still visible in a one-year follow-up.

Magnesium alloys are currently subject to much research for use in biodegradable implant applications. The challenge in this field of material development comprises the design of an alloy that provides adequate mechanical and corrosion properties combined with an excellent biocompatibility. While there are many approaches in current literature only one Mgbased application shows the potential to hit the market. MAGNEZIX Compression Screws are the world’s first approved/CE-certified magnesium-based implants designed for use in biodegradable osteosyntheses applications in humans. Therefore, this paper focusses on challenges and current clinical results achieved by means of degradable compression screws. Insights into the screws’ process chain and approval processes are given. As these innovative screws have already been on the market for 2 years long-term results based on their use in surgery are discussed.

The goal of this review is to bring to the attention of the readership of Magnesium Research another facet of the importance of magnesium, i.e. magnesium-based biomaterials. A concise history of biomaterials and magnesium are thus presented. In addition, historical and current, clinical magnesium-based applications are presented.

Magnesium and magnesium-based alloys in biomaterial applications have shifted again into the focus of the biomedical industry. Thanks to the first CE mark approvals of magnesium-based implants interest will increase further, as the hurdles for approval by e.g. the FDA have been lowered. One important aspect is the understanding/improvement of the production processes of the materials, and their quality. The other, even more important aspect is a deeper understanding of the underlying biological cell and tissue mechanisms in the targeted tissues, which is a prerequisite for facilitating future regulatory applications. Therefore, it is of the utmost importance to establish the correlations between the biological, biochemical, mechanical and microstructural properties of magnesium-based implants. This demands a highly interdisciplinary approach, requiring specialist input from each discipline.

In recent years, much progress has been made on the development of biodegradable magnesium alloys as “smart” implants in cardiovascular and orthopedic applications. Mg-based alloys as biodegradable implants have outstanding advantages over Fe-based and Zn-based ones. However, the extensive applications of Mg-based alloys are still inhibited mainly by their high degradation rates and consequent loss in mechanical integrity. Consequently, extensive studies have been conducted to develop Mg-based alloys with superior mechanical and corrosion performance. This review focuses on the following topics: (i) the design criteria of biodegradable materials; (ii) alloy development strategy; (iii) in vitro performances of currently developed Mg-based alloys; and (iv) in vivo performances of currently developed Mg-based implants, especially Mg-based alloys under clinical trials.

Background: Chevron osteotomies are one of the most common treatment options for Hallux valgus. Different degradable materials have been proposed for fixation, to avoid later hardware removal. This is the first larger series, describing the use of a novel Mg-based metallic biodegradable screw for the fixation of Chevron Osteotomies.

Material and methods: 44 (45 feet) patients with Hallux valgus deformity were included in this prospective study. In all patients a modified Chevron Osteotomie was done. In all but 4 patients (5 feet) the osteotomie was fixed using a Herbert-type Mg-based screw. Clincial and radiological analysis were shedulded preoperative, 6, 12 weeks and 1 year postoperative.

Results: The AOFAS (71–78.5; p = 0.71), FAAM-ADL (76.2– 98.3; p = 0.052), FAAM-Sport (57.2–95.5 (p = 0.03) and painNRS-scale (3.7–0.3; p = 0.096) all showed an improvement. The hallux valgus angle (25.1–10.3; p < 0.0001), intermetatarsal angle (12.8–7.4; p < 0.0001) and sesamoid position (2.3–1.0; p < 0.0001) improved significantly. Radiolucencies could be seen around the implants in all but one after 6 weeks and in 78% after 12 weeks. In seven patients there was some dorsal subluxation, rotation or medial shifting of the metatarsal heads within the first three month. One patient underwent revision.

Conclusion: Mg-based implants can be used for the fixation of distal metatarsal osteotomies, but surgeons starting with the use of these implants should be aware of its proper use and radiographic appearance during healing

The purpose of this paper is to provide a succinct but nevertheless complete mechanistic overview of the various types of magnesium corrosion. The understanding of the corrosion processes of magnesium alloys builds upon our understanding of the corrosion of pure magnesium. This provides an understanding of the types of corrosion exhibited by magnesium alloys, and also of the environmental factors of most importance. This deep understanding is required as a foundation if we are to produce magnesium alloys much more resistant to corrosion than the present alloys. Much has already been achieved, but there is vast scope for improvement. This present analysis can provide a foundation and a theoretical framework for further, much needed research. There is still vast scope both for better fundamental understanding of corrosion processes, engineering usage of magnesium, and also on the corrosion protection of magnesium alloys in service.