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BackgroundRecent 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 in vivo.MethodsA 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.ResultsClinically, 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.ConclusionsModerate 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.

Magnesium alloys are promising implant materials for use in orthopaedic applications. In the present study, screws made of the Mg-alloy ZEK100 (n = 12) were implanted in rabbit tibiae for four and six weeks, respectively. For degradation analysis, in vivo µ-computed tomography (µCT), a determination of the weight changes and SEM/EDX examinations of the screws were performed. Screw retention forces were verified by uniaxial pull-out tests. Additionally, soft-tissue biocompatibility was estimated using routine histological methods (H&E staining) and the immunohistological characterization of B- and T-cells. After six weeks, a 7.5% weight reduction occurred and, in dependence of the implant surrounding, the volume loss (µCT) reached 9.6% (screw head) and 5.0% for the part of the thread in the marrow cavity. Pull-out forces significantly decreased to 44.4% in comparison with the origin value directly after implantation. Soft tissue reactions were characterized by macrophage and lymphocyte infiltration, whereas T-cells as well as B-cells could be observed. In comparison to MgCa0.8-screws, the degradation rate and inflammatory tissue response were increased and the screw holding power was decreased after six weeks. In conclusion, ZEK100-screws seem to be inferior to MgCa0.8-screws, although their initial strength was more appropriate.

BackgroundMagnesium 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.MethodsThe 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.ResultsThe 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.ConclusionBoth 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.

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Biallelic variants in the kaptin gene KPTN were identified recently in individuals with a novel syndrome referred to as autosomal recessive intellectual developmental disorder 41 (MRT41). MRT41 is characterized by developmental delay, predominantly in language development, behavioral abnormalities, and epilepsy. Only about 15 affected individuals have been described in the literature, all with primary or secondary macrocephaly. Using exome sequencing, we identified three different biallelic variants in KPTN in five affected individuals from three unrelated families. In total, two KPTN variants were already reported as a loss of function variants. A novel splice site variant in KPTN was detected in two unrelated families of this study. The core phenotype with neurodevelopment delay was present in all patients. However, macrocephaly was not present in at least one patient. In total, two patients exhibited developmental and epileptic encephalopathies with generalized tonic-clonic seizures that were drug-resistant in one of them. Thus, we further delineate the KPTN-related syndrome, especially emphasizing the severity of epilepsy phenotypes and difficulties in treatment in patients of our cohort.

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