Correction to: Biodegradable magnesium-based screw clinically equivalent to titanium screw in hallux valgus surgery: short term results of the first prospective, randomized, controlled clinical pilot study.

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Bioabsorbable magnesium versus standard titanium compression screws for fixation of distal metatarsal osteotomies - 3 year results of a randomized clinical trial.

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. LEVEL OF EVIDENCE: 2.

Phosphate conversion coating reduces the degradation rate and suppresses side effects of metallic magnesium implants in an animal model.

Magnesium alloys have promising mechanical and biological properties for the development of degradable implants. However, rapid implant corrosion and gas accumulations in tissue impede clinical applications. With time, the implant degradation rate is reduced by a highly biocompatible, phosphate-containing corrosion layer. To circumvent initial side effects after implantation it was attempted to develop a simple in vitro procedure to generate a similarly protective phosphate corrosion layer. To this end magnesium samples were pre-incubated in phosphate solutions. The resulting coating was well adherent during routine handling procedures. It completely suppressed the initial burst of corrosion and it reduced the average in vitro magnesium degradation rate over 56 days almost two-fold. In a small animal model phosphate coatings on magnesium implants were highly biocompatible and abrogated the appearance of gas cavities in the tissue. After implantation, the phosphate coating was replaced by a layer with an elemental composition that was highly similar to the corrosion layer that had formed on plain magnesium implants. The data demonstrate that a simple pre-treatment could improve clinically relevant properties of magnesium-based implants. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1622-1635, 2017.

Magnesium alloys: A stony pathway from intensive research to clinical reality. Different test methods and approval-related considerations.

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. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 329-347, 2017.

Differential magnesium implant corrosion coat formation and contribution to bone bonding.

Magnesium alloys are presently under investigation as promising biodegradable implant materials with osteoconductive properties. To study the molecular mechanisms involved, the potential contribution of soluble magnesium corrosion products to the stimulation of osteoblastic cell differentiation was examined. However, no evidence for the stimulation of osteoblast differentiation could be obtained when cultured mesenchymal precursor cells were differentiated in the presence of metallic magnesium or in cell culture medium containing elevated magnesium ion levels. Similarly, in soft tissue no bone induction by metallic magnesium or by the corrosion product magnesium hydroxide could be observed in a mouse model. Motivated by the comparatively rapid accumulation solid corrosion products physicochemical processes were examined as an alternative mechanism to explain the stimulation of bone growth by magnesium-based implants. During exposure to physiological solutions a structured corrosion coat formed on magnesium whereby the elements calcium and phosphate were enriched in the outermost layer which could play a role in the established biocompatible behavior of magnesium implants. When magnesium pins were inserted into avital bones, corrosion lead to increases in the pull out force, suggesting that the expanding corrosion layer was interlocking with the surrounding bone. Since mechanical stress is a well-established inducer of bone growth, volume increases caused by the rapid accumulation of corrosion products and the resulting force development could be a key mechanism and provide an explanation for the observed stimulatory effects of magnesium-based implants in hard tissue. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 697-709, 2017.

Early results using a biodegradable magnesium screw for modified chevron osteotomies.

This is the first larger study analyzing the use of magnesium-based screws for fixation of modified Chevron osteotomies in hallux valgus surgery. Forty-four 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. Forty patients could be provided with the implant, in four 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 3 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. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:2207-2214, 2016.

Corrosion behavior, biocompatibility and biomechanical stability of a prototype magnesium-based biodegradable intramedullary nailing system.

Implants made of degradable magnesium alloys are a potential alternative to conventional orthopaedic implant materials, e.g. stainless steel or titanium. Intramedullary nails made of the magnesium alloy LAE442 were subjected to cyclic fatigue tests in both distilled water and Hank's Balanced Salt Solution (HBSS) at 37.5°C until implant failure or a limit of 500,000cycles was reached. In distilled water, four of the five nails were still intact after the end of the biomechanical test. In HBSS, a breakage within the first 70,000 bending cycles was observed. Additionally, the degradation rate of this alloy was determined in HBSS according to the weight loss method (0.24±0.12mmyear(-1)) and based on gas release (0.21±0.03mmyear(-1)) with a standard eudiometer. A cytotoxicity test with L929 cells was carried out in accordance with EN ISO 10993-5/12. This test demonstrated sufficient cell viability of the diluted extracts (50%, 25% and 12.5%). The relative metabolic activity of the 100% extract was reduced slightly below 70%, which is classified as a threshold value for cytotoxicity. In conclusion, this in vitro study indicates that intramedullary nails made of LAE442 may not have the required fatigue resistance for load-bearing applications and the development of a corrosion-protective coating may be necessary to prevent early failure of the implant.

Examination of a biodegradable magnesium screw for the reconstruction of the anterior cruciate ligament: A pilot in vivo study in rabbits.

The reconstruction of the anterior cruciate ligament is, for the most part, currently performed with interference screws made of titanium or degradable polymers. The aim of this study was to investigate the use of biodegradable magnesium interference screws for such a procedure because of their known biocompatibility and reported osteoconductive effects. The left tibiae of each of 18 rabbits were implanted with a magnesium-based (MgYREZr-alloy) screw, and another 18 with a titanium-based control. Each group was divided into observation periods of 4, 12 and 24weeks. After sacrifice, µCT scans were acquired to assess the amount of the gas liberated and the degradation rate of the implant. Histological evaluations were performed to investigate the local tissue response adjacent to the implant and to assess the status of the attachment between the tendon and the bone tissue. The µCT scans showed that liberation of gas was most prominent 4weeks after implantation and was significantly decreased by 24weeks. All screws remained in situ and formed a sufficient connection with the tendon and sufficient osseous integration at 24weeks. Histological evaluations showed neither inflammatory reactions nor necrosis of the tendon. The results of this pilot study in rabbits indicate that this magnesium-based interference screw should be considered as an alternative to conventional implant materials.

Magnesium-containing layered double hydroxides as orthopaedic implant coating materials--An in vitro and in vivo study.

The total hip arthroplasty is one of the most common artificial joint replacement procedures. Several different surface coatings have been shown to improve implant fixation by facilitating bone ingrowth and consequently enhancing the longevity of uncemented orthopaedic hip prostheses. In the present study, two different layered double hydroxides (LDHs), Mg-Fe- and Mg-Al-LDH, were investigated as potential magnesium (Mg)-containing coating materials for orthopaedic applications in comparison to Mg hydroxide (Mg(OH)2). In vitro direct cell compatibility tests were carried out using the murine fibroblast cell line NIH 3T3 and the mouse osteosarcoma cell line MG 63. The host response of bone tissue was evaluated in in vivo experiments with nine rabbits. Two cylindrical pellets (3 × 3 mm) were implanted into each femoral condyle of the left hind leg. The samples were analyzed histologically and with µ-computed tomography (µ-CT) 6 weeks after surgery. An in vitro cytotoxicity test determined that more cells grew on the LDH pellets than on the Mg(OH)2-pellets. The pH value and the Mg(2+) content of the cell culture media were increased after incubation of the cells on the degradable samples. The in vivo tests demonstrated the formation of fibrous capsules around Mg(OH)2 and Mg-Fe-LDH. In contrast, the host response of the Mg-Al-LDH samples indicated that this Mg-containing biomaterial is a potential candidate for implant coating.

Biomechanical characteristics of bioabsorbable magnesium-based (MgYREZr-alloy) interference screws with different threads.

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 pull-out 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.

The influence of storage and heat treatment on a magnesium-based implant material: an in vitro and in vivo study.

BACKGROUND: Magnesium alloys are recommended as a potential material for osteosynthesis. It is known that storage-induced property modifications can occur in materials like aluminum. Thus the aim of this study was to analyze the influence of storage durations of up to 48 weeks on the biomechanical, structural, and degradation properties of the degradable magnesium alloy LAE442. METHODS: Extruded implants (n = 104; Ø 2.5 mm × 25 mm) were investigated after storage periods of 0, 12, 24, and 48 weeks in three different sub-studies: (I) immediately after the respective storage duration and after an additional (II) 56 days of in vitro corrosion in simulated body fluid (SFB), and (III) 48 weeks in vivo corrosion in a rabbit model, respectively. In addition, the influence of a T5-heat treatment (206 °C for 15 h in an argon atmosphere) was tested (n = 26; 0 week of storage). Evaluation was performed by three-point bending, scanning electron microscopy, radiography, µ-computed tomography, evaluation of the mean grain size, and contrast analysis of precipitations (such as aluminum or lithium). RESULTS: The heat treatment induced a significant reduction in initial stability, and enhanced the corrosion resistance. In vivo experiments showed a good biocompatibility for all implants. During the storage of up to 48 weeks, no significant changes occurred in the implant properties. CONCLUSIONS: LAE442 implants can be safely used after up to 48 weeks of storage.

Novel magnesium alloy Mg-2La caused no cytotoxic effects on cells in physiological conditions.

Using several different in vitro assays, a new biodegradable magnesium alloy Mg-2La, composed of 98% magnesium and 2% lanthanum, was investigated as a possible implant material for biomedical applications. An in vitro cytotoxicity test, according to EN ISO 10993-5/12, with L929 and human osteoblastic cells identified no toxic effects on cell viability at physiological concentrations (at 50% dilutions and higher). The metabolic activity of human osteoblasts in the 100% extract was decreased to <70% and was therefore rated as cytotoxic. The degradation rates of Mg-2La were evaluated in phosphate buffered saline and four different cell culture media. The degradation rates were shown to be influenced by the composition of the solution, and the addition of fetal bovine serum slightly accelerated the corrosive process. The results of these in vitro experiments suggest that Mg-2La is a promising candidate for use as an orthopedic implant material.

Biodegradation of a magnesium alloy implant in the intercondylar femoral notch showed an appropriate response to the synovial membrane in a rabbit model in vivo.

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.

Comparative in vitro study and biomechanical testing of two different magnesium alloys.

In this in vitro study, magnesium plates of ZEK100 and MgCa0.8 alloy similar to common titanium alloy osteosynthesis plates were investigated as degradable biomedical materials with a focus on primary stability. Immersion tests were performed in Hank's Balanced Salt Solution at 37. The bending strength of the samples was determined using the four-point bending test according to ISO 9585:1990. The initial strength of the noncorroded ZEK100 plate was 11% greater than that of the MgCa0.8 plate; both were approximately 65% weaker than a titanium plate. The bending strength was determined after 48 and 96 h of immersion in Hank's Balanced Salt Solution; both magnesium alloys decreased by approximately 7% after immersion for 96 h. The degradation rate and the Mg(2+) release of ZEK100 were lower than those of MgCa0.8. Strong pitting and filiform corrosion were observed in the MgCa0.8 samples after 96 h of immersion. The surface of the ZEK100 plates exhibited only small areas of filiform corrosion. The results of this in vitro study indicate that the ZEK100 alloy may be more suitable for biomedical 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.

Biodegradable magnesium-based screw clinically equivalent to titanium screw in hallux valgus surgery: short term results of the first prospective, randomized, controlled clinical pilot study.

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.

In vitro corrosion of ZEK100 plates in Hank's Balanced Salt Solution.

BACKGROUND: In recent years magnesium alloys have been intensively investigated as potential resorbable materials with appropriate mechanical and corrosion properties. Particularly in orthopedic research magnesium is interesting because of its mechanical properties close to those of natural bone, the prevention of both stress shielding and removal of the implant after surgery. METHODS: ZEK100 plates were examined in this in vitro study with Hank's Balanced Salt Solution under physiological conditions with a constant laminar flow rate. After 14, 28 and 42 days of immersion the ZEK100 plates were mechanically tested via four point bending test. The surfaces of the immersed specimens were characterized by SEM, EDX and XRD. RESULTS: The four point bending test displayed an increased bending strength after 6 weeks immersion compared to the 2 week group and 4 week group. The characterization of the surface revealed the presence of high amounts of O, P and Ca on the surface and small Mg content. This indicates the precipitation of calcium phosphates with low solubility on the surface of the ZEK100 plates. CONCLUSIONS: The results of the present in vitro study indicate that ZEK100 is a potential candidate for degradable orthopedic implants. Further investigations are needed to examine the degradation behavior.

Biomechanical characterisation of a degradable magnesium-based (MgCa0.8) screw.

Magnesium alloys have been in the focus of research in recent years as degradable biomaterial. The purpose of this study was the biomechanical characterisation of MgCa0.8-screws. The maximum pull out force of screws was determined in a synthetic bone without corrosion and after fixed intervals of corrosion: 24, 48, 72 and 96 h. This in vitro study has been carried out with Hank's solution with a flow rate corresponding to the blood flow in natural bone. A maximum pull out force (F(max)) of 201.5 ± 9.3 N was measured without corrosion. The biomechanical parameter decreased by 30% after 96 h in corrosive medium compared to the non-corrosion group. A maximum load capacity of 28 ± 7.6 N/h was determined. Our biomechanical data suggests that this biodegradable screw provides a promising bone-screw-fixation and has great potential for medical application.

Coating of titanium implants with copolymer supports bone regeneration: a comparative in vivo study in rabbits.

PURPOSE: In modern orthopedics aseptic loosening caused by the formation of micro-wear particles remains a problem for endoprosthetic joint replacements as revision surgery is necessary with corresponding costs and exertions by patients. This study is devoted to the question of how the osseous ingrowth of implants can be supported. It was investigated whether the developed copolymer, p-VBP-co-GMA, coated on the surface of the implants, supports bone healing. In addition, it was analyzed whether covalent linkage of Bone Morphogenetic Protein 2 (BMP-2) to the copolymer layer enhances bone formation. METHODS: Eight adult New Zealand White Rabbits were implanted with four different foils (control, copolymer, copolymer + BMP-2, control + BMP-2) each. The histomorphometric analysis of all samples was made 28 days after implantation. RESULTS: The copolymer had a positive effect on bone remodeling compared to the control group. We observed that the copolymer group had a significantly increased bone volume per tissue volume ratio and bone density to the control group. In contrast, this in-vivo study showed that the immobilization of BMP-2 onto the copolymer layer did not enhance bone healing. The bone volume per tissue volume ratio was decreased as well as the bone density compared to control + BMP-2 group. CONCLUSION: The analysis showed that the bone remodeling process in the copolymer + BMP-2-group is in an early phase comparable to the control group. These results suggest that the coating with the developed copolymer has major potential for medical use as it enhances bone mass around the implant.