In Vivo Corrosion of Two Novel Magnesium Alloys ZEK100 and AX30 and Their Mechanical Suitability as Biodegradable Implants

In magnesium alloys, the components used modify the alloy properties. For magnesium implants in contact with bone, rare earths alloys are commonly examined. These were shown to have a higher corrosion resistance than other alloys and a high mechanical strength, but their exact composition is hard to predict. Therefore a reduction of their content could be favorable. The alloys ZEK100 and AX30 have a reduced content or contain no rare earths at all. The aim of the study was to investigate their in vivo degradation and to assess the suitability of the in vivo μCT for the examination of their corrosion. Implants were inserted in rabbit tibiae. Clinical examinations, X-rays and in vivo μCT scans were done regularly. Afterwards implants were analyzed with REM, electron dispersive X-ray (EDX), weighing and mechanical testing. The in vivo μCT is of great advantage, because it allows a quantification of the corrosion rate and qualitative 3D assessment of the corrosion morphology. The location of the implant has a remarkable effect on the corrosion rate. Due to its mechanical characteristics and its corrosion behavior, ZEK100 was judged to be suitable, while AX30, which displays favorable degradation behavior, has too little mechanical strength for applications in weight bearing bones

Increased accumulation of magnetic nanoparticles by magnetizable implant materials for the treatment of implant-associated complications

Background: In orthopaedic surgery, accumulation of agents such as anti-infectives in the bone as target tissue is difficult. The use of magnetic nanoparticles (MNPs) as carriers principally enables their accumulation via an externally applied magnetic field. Magnetizable implants are principally able to increase the strength of an externally applied magnetic field to reach also deep-seated parts in the body. Therefore, the integration of bone-addressed therapeutics in MNPs and their accumulation at a magnetic orthopaedic implant could improve the treatment of implant related infections. In this study a martensitic steel platelet as implant placeholder was used to examine its accumulation and retention capacity of MNPs in an in vitro experimental set up considering different experimental frame conditions as magnet quantity and distance to each other, implant thickness and flow velocity.Results: The magnetic field strength increased to approximately 112% when a martensitic stainless steel platelet was located between the magnet poles. Therewith a significantly higher amount of magnetic nanoparticles could be accumulated in the area of the platelet compared to the sole magnetic field. During flushing of the tube system mimicking the in vivo blood flow, the magnetized platelet was able to retain a higher amount of MNPs without an external magnetic field compared to the set up with no mounted platelet during flushing of the system. Generally, a higher flow velocity led to lower amounts of accumulated MNPs. A higher quantity of magnets and a lower distance between magnets led to a higher magnetic field strength. Albeit not significantly the magnetic field strength tended to increase with thicker platelets.Conclusion: A martensitic steel platelet significantly improved the attachment of magnetic nanoparticles in an in vitro flow system and therewith indicates the potential of magnetic implant materials in orthopaedic surgery. The use of a remanent magnetic implant material could improve the efficiency of capturing MNPs especially when the external magnetic field is turned off thus facilitating and prolonging the effect. In this way higher drug levels in the target area might be attained resulting in lower inconveniences for the patient

Influence of Heat Treatment on the Degradation Behaviour of Degradable Magnesium Based Implants

Aim of the study was to characterise the influence of heat treatment on the degradation behaviour and stability of degradable magnesium based implants. For this purpose two groups (untreated/ heat treated) of LAE442 pins were separately analysed in an in vitro and in vivo study. The corrosion behaviour was evaluated during 8 weeks degradation in SBF (in vitro) and 48 weeks degradation intramedullary in the rabbit tibia (in vivo). The analyses were made by using μ-computed tomography and three-point-bending tests. Heat treatment led to altered mechanical and corrosion properties of LAE442.While the initial stability declined significantly a reduction of the degradation rate over either in vitro and in vivo evaluation period is determined. If these alterations are still reasonable for osteosynthesis implants remains to be investigated in further projects.DFG/SFB/59

Comparison of morphological changes in efferent lymph nodes after implantation of resorbable and non-resorbable implants in rabbits

<p>Abstract</p> <p>Background</p> <p>Magnesium alloys as biodegradable implant materials received much interest in recent years. It is known that products of implant degradation can induce several types of immune response. Hence, the aim of this study was to examine the morphological changes of efferent lymph nodes after implantation of different resorbable magnesium alloys (MgCa0.8, LAE442) in comparison to commercially available resorbable (PLA) and non-resorbable (titanium) implant materials as well as control groups without implant material.</p> <p>Methods</p> <p>The different implant materials were inserted intramedullary into the rabbit tibia. After postoperative observation periods of three and six months, popliteal lymph nodes were examined histologically and immunhistologically and compared to lymph nodes of sham operated animals and animals without surgery. Haematoxylin and eosin staining was performed for cell differentiation. Mouse anti-CD79α and rat anti-CD3 monoclonal primary antibodies were used for B- and T-lymphocyte detection, mouse anti-CD68 primary antibodies for macrophage detection. Evaluation of all sections was performed applying a semi quantitative score.</p> <p>Results</p> <p>The histological evaluation demonstrated low and moderate levels of morphological changes for both magnesium alloys (LAE442 and MgCa0.8). Higher than moderate values were reached for titanium in sinus histiocytosis and histiocytic apoptosis (3 months) and for PLA in histiocytic apoptosis (3 and 6 months). The immune response to all investigated implants had a non-specific character and predominantly was a foreign-body reaction. LAE442 provoked the lowest changes which might be due to a lower degradation rate in comparison to MgCa0.8. Therewith it is a promising candidate for implants with low immunogenic potential.</p> <p>Conclusion</p> <p>Both examined magnesium alloys did not cause significantly increased morphological changes in efferent lymph nodes in comparison to the widely used implant materials titanium and PLA. LAE442 induced even lower immunological reactions. Therewith MgCa0.8 and especially LAE442 are appropriate candidates for biomedical use.</p

Evaluation of the soft tissue biocompatibility of MgCa0.8 and surgical steel 316L in vivo: a comparative study in rabbits

<p>Abstract</p> <p>Background</p> <p>Recent studies have shown the potential suitability of magnesium alloys as biodegradable implants. The aim of the present study was to compare the soft tissue biocompatibility of MgCa0.8 and commonly used surgical steel <it>in vivo</it>.</p> <p>Methods</p> <p>A biodegradable magnesium calcium alloy (MgCa0.8) and surgical steel (S316L), as a control, were investigated. Screws of identical geometrical conformation were implanted into the tibiae of 40 rabbits for a postoperative follow up of two, four, six and eight weeks. The tibialis cranialis muscle was in direct vicinity of the screw head and thus embedded in paraffin and histologically and immunohistochemically assessed. Haematoxylin and eosin staining was performed to identify macrophages, giant cells and heterophil granulocytes as well as the extent of tissue fibrosis and necrosis. Mouse anti-CD79α and rat anti-CD3 monoclonal primary antibodies were used for B- and T-lymphocyte detection. Evaluation of all sections was performed by applying a semi-quantitative score.</p> <p>Results</p> <p>Clinically, both implant materials were tolerated well. Histology revealed that a layer of fibrous tissue had formed between implant and overlying muscle in MgCa0.8 and S316L, which was demarcated by a layer of synoviocyte-like cells at its interface to the implant. In MgCa0.8 implants cavities were detected within the fibrous tissue, which were surrounded by the same kind of cell type. The thickness of the fibrous layer and the amount of tissue necrosis and cellular infiltrations gradually decreased in S316L. In contrast, a decrease could only be noted in the first weeks of implantation in MgCa0.8, whereas parameters were increasing again at the end of the observation period. B-lymphocytes were found more often in MgCa0.8 indicating humoral immunity and the presence of soluble antigens. Conversely, S316L displayed a higher quantity of T-lymphocytes.</p> <p>Conclusions</p> <p>Moderate inflammation was detected in both implant materials and resolved to a minimum during the first weeks indicating comparable biocompatibility for MgCa0.8 and S316L. Thus, the application of MgCa0.8 as biodegradable implant material seems conceivable. Since the inflammatory parameters were re-increasing at the end of the observation period in MgCa0.8 it is important to observe the development of inflammation over a longer time period in addition to the present study.</p

Preparation and PET/CT imaging of implant directed 68Ga-labeled magnetic nanoporous silica nanoparticles

Background: Implant infections caused by biofilm forming bacteria are a major threat in orthopedic surgery. Delivering antibiotics directly to an implant affected by a bacterial biofilm via superparamagnetic nanoporous silica nanoparticles could present a promising approach. Nevertheless, short blood circulation half-life because of rapid interactions of nanoparticles with the host’s immune system hinder them from being clinically used. The aim of this study was to determine the temporal in vivo resolution of magnetic nanoporous silica nanoparticle (MNPSNP) distribution and the effect of PEGylation and clodronate application using PET/CT imaging and gamma counting in an implant mouse model. Methods: PEGylated and non-PEGylated MNPSNPs were radiolabeled with gallium-68 (68Ga), implementing the chelator tris(hydroxypyridinone). 36 mice were included in the study, 24 mice received a magnetic implant subcutaneously on the left and a titanium implant on the right hind leg. MNPSNP pharmacokinetics and implant accumulation was analyzed in dependence on PEGylation and additional clodronate application. Subsequently gamma counting was performed for further final analysis. Results: The pharmacokinetics and biodistribution of all radiolabeled nanoparticles could clearly be visualized and followed by dynamic PET/CT imaging. Both variants of 68Ga-labeled MNPSNP accumulated mainly in liver and spleen. PEGylation of the nanoparticles already resulted in lower liver uptakes. Combination with macrophage depletion led to a highly significant effect whereas macrophage depletion alone could not reveal significant differences. Although MNPSNP accumulation around implants was low in comparison to the inner organs in PET/CT imaging, gamma counting displayed a significantly higher %I.D./g for the tissue surrounding the magnetic implants compared to the titanium control. Additional PEGylation and/or macrophage depletion revealed no significant differences regarding nanoparticle accumulation at the implantation site. Conclusion: Tracking of 68Ga-labeled nanoparticles in a mouse model in the first critical hours post-injection by PET/CT imaging provided a better understanding of MNPSNP distribution, elimination and accumulation. Although PEGylation increases circulation time, nanoparticle accumulation at the implantation site was still insufficient for infection treatment and additional efforts are needed to increase local accumulation

Biodistribution, biocompatibility and targeted accumulation of magnetic nanoporous silica nanoparticles as drug carrier in orthopedics

Background: In orthopedics, the treatment of implant-associated infections represents a high challenge. Especially, potent antibacterial effects at implant surfaces can only be achieved by the use of high doses of antibiotics, and still often fail. Drug-loaded magnetic nanoparticles are very promising for local selective therapy, enabling lower systemic antibiotic doses and reducing adverse side effects. The idea of the following study was the local accumulation of such nanoparticles by an externally applied magnetic field combined with a magnetizable implant. The examination of the biodistribution of the nanoparticles, their effective accumulation at the implant and possible adverse side effects were the focus. In a BALB/c mouse model (n = 50) ferritic steel 1.4521 and Ti90Al6V4 (control) implants were inserted subcutaneously at the hindlimbs. Afterwards, magnetic nanoporous silica nanoparticles (MNPSNPs), modified with rhodamine B isothiocyanate and polyethylene glycol-silane (PEG), were administered intravenously. Directly/1/7/21/42 day(s) after subsequent application of a magnetic field gradient produced by an electromagnet, the nanoparticle biodistribution was evaluated by smear samples, histology and multiphoton microscopy of organs. Additionally, a pathohistological examination was performed. Accumulation on and around implants was evaluated by droplet samples and histology. Results: Clinical and histological examinations showed no MNPSNP-associated changes in mice at all investigated time points. Although PEGylated, MNPSNPs were mainly trapped in lung, liver, and spleen. Over time, they showed two distributional patterns: early significant drops in blood, lung, and kidney and slow decreases in liver and spleen. The accumulation of MNPSNPs on the magnetizable implant and in its area was very low with no significant differences towards the control. Conclusion: Despite massive nanoparticle capture by the mononuclear phagocyte system, no significant pathomorphological alterations were found in affected organs. This shows good biocompatibility of MNPSNPs after intravenous administration. The organ uptake led to insufficient availability of MNPSNPs in the implant region. For that reason, among others, the nanoparticles did not achieve targeted accumulation in the desired way, manifesting future research need. However, with different conditions and dimensions in humans and further modifications of the nanoparticles, this principle should enable reaching magnetizable implant surfaces at any time in any body region for a therapeutic reason. © 2020 The Author(s)

Influence of stress on the degradation behavior of Mg LAE442 implant systems

In this paper the performance of a magnesium based implant system is analyzed. A special emphasis is placed on the impact of stress on the corrosion behavior of the magnesium alloy. An implant system containing a plate and 4 corresponding screws is machined from Mg LAE442. Its corrosion behavior is tested in-vivo in New Zealand White Rabbits for 6 and 12 weeks of implantation. The plate is monocortically fixated on the medial tibia. At the interface between screw and plate increased corrosion is observed. This phenomenon is stronger on the caudal side of the screw. Parallel to the in-vivo test the influence of stress load on the corrosion rate is analyzed for LAE442 in in-vitro tests. Compressive load is applied on cylindrical specimens in axial direction and the corrosion rate is measured in 0.9 wt% NaCl solution by eudiometry and mass loss. Additionally rectangular samples are bent to apply tensile stress on the surface. A drop of 5 wt% NaCl is deposited on the surface and the corrosion is evaluated by microscopic images. It is shown that stress essentially influences the corrosion rate. While tensile stress decreases the corrosion, compressive stress leads to higher corrosion rates