Detailing the influence of PEO-coated biodegradable Mg-based implants on the lacuno-canalicular network in sheep bone: A pilot study.

An increasing prevalence of bone-related injuries and aging geriatric populations continue to drive the orthopaedic implant market. A hierarchical analysis of bone remodelling after material implantation is necessary to better understand the relationship between implant and bone. Osteocytes, which are housed and communicate through the lacuno-canalicular network (LCN), are integral to bone health and remodelling processes. Therefore, it is essential to examine the framework of the LCN in response to implant materials or surface treatments. Biodegradable materials offer an alternative solution to permanent implants, which may require revision or removal surgeries. Magnesium alloys have resurfaced as promising materials due to their bone-like properties and safe degradation in vivo. To further tailor their degradation capabilities, surface treatments such as plasma electrolytic oxidation (PEO) have demonstrated to slow degradation. For the first time, the influence of a biodegradable material on the LCN is investigated by means of non-destructive 3D imaging. In this pilot study, we hypothesize noticeable variations in the LCN caused by altered chemical stimuli introduced by the PEO-coating. Utilising synchrotron-based transmission X-ray microscopy, we have characterised morphological LCN differences around uncoated and PEO-coated WE43 screws implanted into sheep bone. Bone specimens were explanted after 4, 8, and 12 weeks and regions near the implant surface were prepared for imaging. Findings from this investigation indicate that the slower degradation of PEO-coated WE43 induces healthier lacunar shapes within the LCN. However, the stimuli perceived by the uncoated material with higher degradation rates induces a greater connected LCN better prepared for bone disturbance.

Multiscale morphological analysis of bone microarchitecture around Mg-10Gd implants.

The utilization of biodegradable magnesium (Mg)-based implants for restoration of bone function following trauma represents a transformative approach in orthopaedic application. One such alloy, magnesium-10 weight percent gadolinium (Mg-10Gd), has been specifically developed to address the rapid degradation of Mg while enhancing its mechanical properties to promote bone healing. Previous studies have demonstrated that Mg-10Gd exhibits favorable osseointegration; however, it exhibits distinct ultrastructural adaptation in comparison to conventional implants like titanium (Ti). A crucial aspect that remains unexplored is the impact of Mg-10Gd degradation on the bone microarchitecture. To address this, we employed hierarchical three-dimensional imaging using synchrotron radiation in conjunction with image-based finite element modelling. By using the methods outlined, the vascular porosity, lacunar porosity and the lacunar-canaliculi network (LCN) morphology of bone around Mg-10Gd in comparison to Ti in a rat model from 4 weeks to 20 weeks post-implantation was investigated. Our investigation revealed that within our observation period, the degradation of Mg-10Gd implants was associated with significantly lower (p < 0.05) lacunar density in the surrounding bone, compared to Ti. Remarkably, the LCN morphology and the fluid flow analysis did not significantly differ for both implant types. In summary, a more pronounced lower lacunae distribution rather than their morphological changes was detected in the surrounding bone upon the degradation of Mg-10Gd implants. This implies potential disparities in bone remodelling rates when compared to Ti implants. Our findings shed light on the intricate relationship between Mg-10Gd degradation and bone microarchitecture, contributing to a deeper understanding of the implications for successful osseointegration.

Degradation behavior and osseointegration of Mg-Zn-Ca screws in different bone regions of growing sheep: a pilot study.

Magnesium (Mg)-based implants are highly attractive for the orthopedic field and may replace titanium (Ti) as support for fracture healing. To determine the implant-bone interaction in different bony regions, we implanted Mg-based alloy ZX00 (Mg < 0.5 Zn < 0.5 Ca, in wt%) and Ti-screws into the distal epiphysis and distal metaphysis of sheep tibiae. The implant degradation and osseointegration were assessed in vivo and ex vivo after 4, 6 and 12 weeks, using a combination of clinical computed tomography, medium-resolution micro computed tomography (µCT) and high-resolution synchrotron radiation µCT (SRµCT). Implant volume loss, gas formation and bone growth were evaluated for both implantation sites and each bone region independently. Additionally, histological analysis of bone growth was performed on embedded hard-tissue samples. We demonstrate that in all cases, the degradation rate of ZX00-implants ranges between 0.23 and 0.75 mm/year. The highest degradation rates were found in the epiphysis. Bone-to-implant contact varied between the time points and bone types for both materials. Mostly, bone-volume-to-total-volume was higher around Ti-implants. However, we found an increased cortical thickness around the ZX00-screws when compared with the Ti-screws. Our results showed the suitability of ZX00-screws for implantation into the distal meta- and epiphysis.

Radiofrequency induced heating of biodegradable orthopaedic screw implants during magnetic resonance imaging.

Magnesium (Mg)-based implants have re-emerged in orthopaedic surgery as an alternative to permanent implants. Literature reveals little information on how the degradation of biodegradable implants may introduce safety implications for patient follow-up using medical imaging. Magnetic resonance imaging (MRI) benefits post-surgery monitoring of bone healing and implantation sites. Previous studies demonstrated radiofrequency (RF) heating of permanent implants caused by electromagnetic fields used in MRI. Our investigation is the first to report the effect of the degradation layer on RF-induced heating of biodegradable orthopaedic implants. WE43 orthopaedic compression screws underwent in vitro degradation. Imaging techniques were applied to assess the corrosion process and the material composition of the degraded screws. Temperature measurements were performed to quantify implant heating with respect to the degradation layer. For comparison, a commercial titanium implant screw was used. Strongest RF induced heating was observed for non-degraded WE43 screw samples. Implant heating had shown to decrease with the formation of the degradation layer. No statistical differences were observed for heating of the non-degraded WE43 material and the titanium equivalent. The highest risk of implant RF heating is most pronounced for Mg-based screws prior to degradation. Amendment to industry standards for MRI safety assessment is warranted to include biodegradable materials.

Development of a Bioreactor-Coupled Flow-Cell Setup for 3D In Situ Nanotomography of Mg Alloy Biodegradation.

Functional materials feature hierarchical microstructures that define their unique set of properties. The prediction and tailoring of these require a multiscale knowledge of the mechanistic interaction of microstructure and property. An important material in this respect is biodegradable magnesium alloys used for implant applications. To correlate the relationship between the microstructure and the nonlinear degradation process, high-resolution in situ three-dimensional (3D) imaging experiments must be performed. For this purpose, a novel experimental flow cell is presented which allows for the in situ 3D-nano imaging of the biodegradation process of materials with nominal resolutions below 100 nm using nanofocused hard X-ray radiation from a synchrotron source. The flow cell setup can operate under adjustable physiological and hydrodynamic conditions. As a model material, the biodegradation of thin Mg-4Ag wires in simulated body fluid under physiological conditions and a flow rate of 1 mL/min is studied. The use of two full-field nanotomographic imaging techniques, namely transmission X-ray microscopy and near-field holotomography, is compared, revealing holotomography as the superior imaging technique for this purpose. Additionally, the importance of maintaining physiological conditions is highlighted by the preliminary results. Supporting measurements using electron microscopy to investigate the chemical composition of the samples after degradation are performed.

In vitro and in vivo degradation behavior of Mg-0.45Zn-0.45Ca (ZX00) screws for orthopedic applications.

Magnesium (Mg) alloys have become a potential material for orthopedic implants due to their unnecessary implant removal, biocompatibility, and mechanical integrity until fracture healing. This study examined the in vitro and in vivo degradation of an Mg fixation screw composed of Mg-0.45Zn-0.45Ca (ZX00, in wt.%). With ZX00 human-sized implants, in vitro immersion tests up to 28 days under physiological conditions, along with electrochemical measurements were performed for the first time. In addition, ZX00 screws were implanted in the diaphysis of sheep for 6, 12, and 24 weeks to assess the degradation and biocompatibility of the screws in vivo. Using scanning electron microscopy (SEM) coupled with energy dispersive X-ray spectroscopy (EDX), micro-computed tomography (µCT), X-ray photoelectron spectroscopy (XPS), and histology, the surface and cross-sectional morphologies of the corrosion layers formed, as well as the bone-corrosion-layer-implant interfaces, were analyzed. Our findings from in vivo testing demonstrated that ZX00 alloy promotes bone healing and the formation of new bone in direct contact with the corrosion products. In addition, the same elemental composition of corrosion products was observed for in vitro and in vivo experiments; however, their elemental distribution and thicknesses differ depending on the implant location. Our findings suggest that the corrosion resistance was microstructure-dependent. The head zone was the least corrosion-resistant, indicating that the production procedure could impact the corrosion performance of the implant. In spite of this, the formation of new bone and no adverse effects on the surrounding tissues demonstrated that the ZX00 is a suitable Mg-based alloy for temporary bone implants.

Implant degradation of low-alloyed Mg-Zn-Ca in osteoporotic, old and juvenile rats.

Implant removal is unnecessary for biodegradable magnesium (Mg)-based implants and, therefore, the related risk for implant-induced fractures is limited. Aging, on the other hand, is associated with low bone-turnover and decreased bone mass and density, and thus increased fracture risk. Osteoporosis is accompanied by Mg deficiency, therefore, we hypothesized that Mg-based implants may support bone formation by Mg2+ ion release in an ovariectomy-induced osteoporotic rat model. Hence, we investigated osseointegration and implant degradation of a low-alloyed, degrading Mg-Zn-Ca implant (ZX00) in ovariectomy-induced osteoporotic (Osteo), old healthy (OH), and juvenile healthy (JH) groups of female Sprague Dawley rats via in vivo micro-computed tomography (µCT). For the Osteo rats, we demonstrate diminished trabecular bone already after 8 weeks upon ovariectomy and significantly enhanced implant volume loss, with correspondingly pronounced gas formation, compared to the OH and JH groups. Sclerotic rim development was observed in about half of the osteoporotic rats, suggesting a prevention from foreign-body and osteonecrosis development. Synchrotron radiation-based µCT confirmed lower bone volume fractions in the Osteo group compared to the OH and JH groups. Qualitative histological analysis additionally visualized the enhanced implant degradation in the Osteo group. To date, ZX00 provides an interesting implant material for young and older healthy patients, but it may not be of advantage in pharmacologically untreated osteoporotic conditions. STATEMENT OF SIGNIFICANCE: Magnesium-based implants are promising candidates for treatment of osteoporotic fractures because of their biodegradable, biomechanical, anti-bacterial and bone regenerative properties. Here we investigate magnesium‒zinc‒calcium implant materials in a rat model with ovariectomy-induced osteoporosis (Osteo group) and compare the related osseointegration and implant degradation with the results obtained for old healthy (OH) and juvenile healthy (JH) rats. The work applied an appropriate disease model for osteoporosis and focused in particular on long-term implant degradation for different bone conditions. Enhanced implant degradation and sclerotic rim formation was observed in osteoporotic rats, which illustrates that the setting of different bone models generates significantly modified clinical outcome. It further illustrated that these differences must be taken into account in future biodegradable implant development.

Scaling the U-net: segmentation of biodegradable bone implants in high-resolution synchrotron radiation microtomograms.

Highly accurate segmentation of large 3D volumes is a demanding task. Challenging applications like the segmentation of synchrotron radiation microtomograms (SRµCT) at high-resolution, which suffer from low contrast, high spatial variability and measurement artifacts, readily exceed the capacities of conventional segmentation methods, including the manual segmentation by human experts. The quantitative characterization of the osseointegration and spatio-temporal biodegradation process of bone implants requires reliable, and very precise segmentation. We investigated the scaling of 2D U-net for high resolution grayscale volumes by three crucial model hyper-parameters (i.e., the model width, depth, and input size). To leverage the 3D information of high-resolution SRµCT, common three axes prediction fusing is extended, investigating the effect of adding more than three axes prediction. In a systematic evaluation we compare the performance of scaling the U-net by intersection over union (IoU) and quantitative measurements of osseointegration and degradation parameters. Overall, we observe that a compound scaling of the U-net and multi-axes prediction fusing with soft voting yields the highest IoU for the class "degradation layer". Finally, the quantitative analysis showed that the parameters calculated with model segmentation deviated less from the high quality results than those obtained by a semi-automatic segmentation method.