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The nanostructural adaptation of bone is crucial for its biocompatibility with orthopedic implants. The bone nanostructure also determines its mechanical properties and performance. However, the bone's temporal and spatial nanoadaptation around degrading implants remains largely unknown. Here, we present insights into this important bone adaptation by applying scanning electron microscopy, elemental analysis, and small-angle X-ray scattering tensor tomography (SASTT). We extend the novel SASTT reconstruction method and provide a 3D scattering reciprocal space map per voxel of the sample's volume. From this reconstruction, parameters such as the thickness of the bone mineral particles are quantified, which provide additional information on nanostructural adaptation of bone during healing. We selected a rat femoral bone and a degrading ZX10 magnesium implant as model system, and investigated it over the course of 18 months, using a sham as control. We observe that the bone's nanostructural adaptation starts with an initially fast interfacial bone growth close to the implant, which spreads by a re-orientation of the nanostructure in the bone volume around the implant, and is consolidated in the later degradation stages. These observations reveal the complex bulk bone-implant interactions and enable future research on the related biomechanical bone responses. Statement of significance Traumatic bone injuries are among the most frequent causes of surgical treatment, and often require the placement of an implant. The ideal implant supports and induces bone formation, while being mechanically and chemically adapted to the bone structure, ensuring a gradual load transfer. While magnesium implants fulfill these requirements, the nanostructural changes during bone healing and implant degradation remain not completely elucidated. Here, we unveil these processes in rat femoral bones with ZX10 magnesium implants and show different stages of bone healing in such a model system., Acta Biomaterialia, 134, ISSN:1742-7061, ISSN:1878-7568

The nanostructural adaptation of bone is crucial for its compatibility with orthopedic implants. The bone’s nanostructure determines its mechanical properties, however little is known about its temporal and spatial adaptation in degrading implants. This study presents insights into this adaptation by applying electron microscopy, elemental analysis, and small-angle X-ray scattering tensor-tomography (SASTT). We extend the SASTT reconstruction to multiple radii of the reciprocal space vector q, providing a 3D reciprocal-space map per voxel. Each scattering curve is spatially linked to one voxel in the volume, and properties such as the thickness of the mineral particles are quantified. This reconstruction provides information on nanostructural adaptation during healing around a degrading ZX10 magnesium implant over the course of 18 months, using a sham as control. The nanostructural adaptation process is observed to start with an initially fast interfacial organization towards the implant direction, followed by a substantial reorganization of the volume around the implant, and an adaptation in the later degradation stages. The study sheds light on the complex bone-implant interaction in 3D, allowing a more guided approach towards the design of future implant materials, which are expected to be of great interest for further clinical studies on the bone-implant interaction.TOC text and figureDegrading Magnesium implants are mechanically and chemically well adapted orthopedic implant materials and ensure a gradual load transfer during bone healing due to their degradation. The impact of the implant degradation on the bone nanostructure is however not fully understood. This study unveils the processes 3D and shows different stages of bone healing.

Item does not contain fulltext Fracture treatment in children needs new implant materials to overcome disadvantages associated with removal surgery. Magnesium-based implants constitute a biocompatible and bioresorbable alternative. In adults and especially in children, implant safety needs to be evaluated. In children the bone turnover rate is higher and implant material might influence growth capacity, and the long-term effect of accumulated particles or ions is more critical due to the host's prolonged post-surgery lifespan. In this study we aimed to investigate the degradation behavior of ZX00 (Mg-0.45Zn-0.45Ca; in wt.%) in a small and a large animal model to find out whether there is a difference between the two models (i) in degradation rate and (ii) in bone formation and in-growth. Our results 6, 12 and 24weeks after ZX00 implantation showed no negative effects on bone formation and in-growth, and no adverse effects such as fibrotic or sclerotic encapsulation. The degradation rate did not significantly differ between the two growing-animal models, and both showed slow and homogeneous degradation performance. Our conclusion is that small animal models may be sufficient to investigate degradation rates and provide preliminary evidence on bone formation and in-growth of implant materials in a growing-animal model. STATEMENT OF SIGNIFICANCE: The safety of implant material is of the utmost importance, especially in children, who have enhanced bone turnover, more growth capacity and longer postoperative lifespans. Magnesium (Mg)-based implants have long been of great interest in pediatric orthopedic and trauma surgery, due to their good biocompatibility, biodegradability and biomechanics. In the study documented in this manuscript we investigated Mg-Zn-Ca implant material without rare-earth elements, and compared its outcome in a small and a large growing-animal model. In both models we observed bone formation and in-growth which featured no adverse effects such as fibrotic or sclerotic encapsulation, and slow homogeneous degradation performance of the Mg-based implant material.

Mg-based biodegradable materials are considered promising candidates in the paediatric field due to their favourable mechanical and biological properties and their biodegrading potential that makes a second surgery for implant removal unnecessary. In many cases the surgical fixation technique requires a crossing of the growth plate by the implant in order to achieve an adequate fragment replacement or fracture stabilisation. This study investigates the kinetics of slowly and rapidly degrading Mg alloys in a transphyseal rat model, and also reports on their dynamics in the context of the physis and consecutive bone growth. Twenty-six male Sprague–Dawley rats received either a rapidly degrading (ZX50; n = 13) or a slowly degrading (WZ21; n = 13) Mg alloy, implanted transphyseal into the distal femur. The contralateral leg was drilled in the same manner and served as a direct sham specimen. Degradation behaviour, gas formation, and leg length were measured by continuous in vivo micro CT for up to 52 weeks, and additional high-resolution µCT (HRS) scans and histomorphological analyses of the growth plate were performed. The growth plate was locally destroyed and bone growth was significantly diminished by the fast degradation of ZX50 implants and the accompanying release of large amounts of hydrogen gas. In contrast, WZ21 implants showed homogenous and moderate degradation performance, and the effect on bone growth did not differ significantly from a single drill-hole defect. Statement of Significance This study is the first that reports on the effects of degrading magnesium implants on the growth plate in a living animal model. The results show that high evolution of hydrogen gas due to rapid Mg degradation can damage the growth plate substantially. Slow degradation, however, such as seen for WZ21 alloys, does not affect the growth plate more than drilling alone, thus meeting one important prerequisite for deployment in paediatric osteosynthesis.

Biodegradable materials are under investigation due to their promising properties for biomedical applications as implant material. In the present study, two binary magnesium (Mg) alloys (Mg2Ag and Mg10Gd) and pure Mg (99.99%) were used in order to compare the degradation performance of the materials in in vitro to in vivo conditions. In vitro analysis of cell distribution and viability was performed on discs of pure Mg, Mg2Ag and Mg10Gd. The results verified viable pre-osteoblast cells on all three alloys and no obvious toxic effect within the first two weeks. The degradation rates in in vitro and in vivo conditions (Sprague–Dawley® rats) showed that the degradation rates differ especially in the 1st week of the experiments. While in vitro Mg2Ag displayed the fastest degradation rate, in vivo, Mg10Gd revealed the highest degradation rate. After four weeks of in vitro immersion tests, the degradation rate of Mg2Ag was significantly reduced and approached the values of pure Mg and Mg10Gd. Interestingly, after 4 weeks the estimated in vitro degradation rates approximate in vivo values. Our systematic experiment indicates that a correlation between in vitro and in vivo observations still has some limitations that have to be considered in order to perform representative in vitro experiments that display the in vivo situation.

Aim of this study was to evaluate the response of bone to novel biodegradable polymeric composite implants in the femora of growing rats. Longitudinal observation of bone reaction at the implant site (BV/TV) as well as resorption of the implanted pins were monitored using in vivo micro-focus computed tomography (µCT). After 12, 24 and 36 weeks femora containing the implants were explanted, scanned with high resolution ex vivo µCT, and the surface roughness of the implants was measured to conclude on the ingrowth capability for bone tissue. Scanning electron microscope (SEM) and energy dispersive X-ray spectroscopy (EDX) were used to observe changes on the surface of Polyhydroxybutyrate (PHB) during degradation and cell ingrowth. Four different composites with zirconium dioxide (ZrO2) and Herafill(®) were compared. After 36 weeks in vivo, none of the implants did show significant degradation. The PHB composite with ZrO2 and a high percentage (30%) of Herafill® as well as the Mg-alloy WZ21 showed the highest values of bone accumulation (increased BV/TV) around the implant. The lowest value was measured in PHB with 3% ZrO2 containing no Herafill®. Roughness measurements as well as EDX and SEM imaging could not reveal any changes on the PHB composites׳ surfaces. Biomechanical parameters, such as the adhesion strength between bone and implant were determined by measuring the shear strength as well as push-out energy of the bone-implant interface. The results showed that improvement of these mechanical properties of the studied PHBs P3Z, P3Z10H and P3Z30H is necessary in order to obtain appropriate load-bearing material. The moduli of elasticity, tensile strength and strain properties of the PHB composites are close to that of bone and thus promising. Compared to clinically used PLGA, PGA and PLA materials, their additional benefit is an unchanged local pH value during degradation, which makes them well tolerated by cells and immune system. They might be used successfully for personalized 3D printed implants or as coatings of rapidly dissolving implants.

This study investigates the degradation performance of three Fe-based materials in a growing rat skeleton over a period of 1 year. Pins of pure Fe and two Fe-based alloys (Fe-10 Mn-1Pd and Fe-21 Mn-0.7C-1Pd, in wt.%) were implanted transcortically into the femur of 38 Sprague-Dawley rats and inspected after 4, 12, 24 and 52 weeks. The assessment was performed by ex vivo microfocus computed tomography, weight-loss determination, surface analysis of the explanted pins and histological examination. The materials investigated showed signs of degradation; however, the degradation proceeded rather slowly and no significant differences between the materials were detected. We discuss these unexpected findings on the basis of fundamental considerations regarding iron corrosion. Dense layers of degradation products were formed on the implants' surfaces, and act as barriers against oxygen transport. For the degradation of iron, however, the presence of oxygen is an indispensable prerequisite. Its availability is generally a critical factor in bony tissue and rather limited there, i.e. in the vicinity of our implants. Because of the relatively slow degradation of both pure Fe and the Fe-based alloys, their suitability for bulk temporary implants such as those in osteosynthesis applications appears questionable.

In the present paper, first results of the influence of the degradation of biodegradable materials on the hardness of the bone are presented in detail. For this purpose, different materials (Mg, Ti and biopolymers) were implanted into the femora of growing rats and bone cross sections were examined for the micro-hardness (MH). The aim of the present paper was to examine the mechanical response of the bone areas surrounding the implant at defined sites and at specified periods after implantation. A special focus was set on Mg alloys. In earlier in-vitro and in-vivo studies, an accumulation of Magnesium in the vicinity of the implant was detected by using different techniques. Therefore, micro-hardness measurements were performed, and the mechanical strength of bone was correlated with the exchange of Magnesium and Calcium in Hydroxyapatite. After the operation and implantation, the micro-hardness values became temporarily lower, but after complete degradation of the implants, the values were identical with those of specimens containing no implants.

Flexible intramedullary nailing (FIN) is a minimally invasive and widespread standard method for osteosynthesis of pediatric long bone fractures. In the case of unstable fractures of the lower extremity, interlocking systems need to be used to prevent axial shortening and subsequent perforation of the nail at its insertion site. In the present study, four different screw-fixed interlocking systems for FINs (Hofer TwinPlug with two 3-mm titanium interlocking screws, Hofer FixPlug with 3-mm titanium interlocking screw, Hofer Plug with 3.5-mm titanium interlocking screw, and Hofer Plug with 3-mm titanium interlocking screw) in comparison with the commonly used Ender stainless steel nails (locked with 3.5-mm screw) were experimentally investigated in cadaveric lamb tibiae, regarding their load characteristics and failure modes in the case of heavy loading. The specimens were subjected to sequential axial cyclic loading of 5000cycles with stepwise increase of the load amplitude until failure. Migration of locking screws and internal damage of bone tissue was quantified by micro-computed tomography (CT) imaging. Ender nails failed on average at a peak load of 800 N, TwinPlugs at 1367 N, FixPlugs at 1222 N, Plugs 3.5mm at 1225 N and Plugs 3.0mm at 971 N. TwinPlugs, FixPlugs, and Plugs 3.5mm failed in a slow manner over several hundred loading cycles, whereas Ender nails and Plugs 3.0mm exhibited abrupt failure without any prior indication. Our results confirm that axial stability of FIN can be further improved by screw-fixed plugs by simultaneously avoiding shortcomings of an eye-locked system, which the Ender nails are. Considering biomechanical results, plug interlocking systems with 3.5-mm screws should be favored over conventional Ender nails and plugs with 3-mm screws.

Bioresorbable magnesium materials are widely investigated because of their promising properties as orthopedic devices. Pure magnesium (99.99%) and two binary magnesium alloys (Mg2Ag and Mg10Gd) were used to investigate the degradation behavior, the bone adherence and bone-implant interface mechanics of these materials in growing Sprague-Dawley® rats in a long-term study of 36 weeks. In vivo micro-computed tomography (μCT) scans were performed at specific time points to observe the longitudinal degradation of each alloy within the same animal. Pin volume and surface, gas volume and degradation rates were calculated. The results showed a slower degradation of pure magnesium and Mg2Ag in comparison to the fast disintegrating Mg10Gd. Changes in bone morphology were determined by high resolution ex vivo μCT scans and bone sections stained with Toluidine blue. Pure magnesium and Mg2Ag were well integrated and surrounded by bony tissue 24 weeks after implantation. On the contrary, Mg10Gd remnants were surrounded by fibrous and bone tissue. Push-out tests revealed higher bone-implant-interface strengths of pure magnesium pins compared to Mg2Ag and Mg10Gd. Mg10Gd induces less beneficial tissue reactions, while Mg2Ag showed adequate biodegradation and no adverse reactions in bone healing process which might be promising as an orthopedic device.