Multi-modal investigation of the bone micro- and ultrastructure, and elemental distribution in the presence of Mg-xGd screws at mid-term healing stages.

Magnesium (Mg) - based alloys are becoming attractive materials for medical applications as temporary bone implants for support of fracture healing, e.g. as a suture anchor. Due to their mechanical properties and biocompatibility, they may replace titanium or stainless-steel implants, commonly used in orthopedic field. Nevertheless, patient safety has to be assured by finding a long-term balance between metal degradation, osseointegration, bone ultrastructure adaptation and element distribution in organs. In order to determine the implant behavior and its influence on bone and tissues, we investigated two Mg alloys with gadolinium contents of 5 and 10 wt percent in comparison to permanent materials titanium and polyether ether ketone. The implants were present in rat tibia for 10, 20 and 32 weeks before sacrifice of the animal. Synchrotron radiation-based micro computed tomography enables the distinction of features like residual metal, degradation layer and bone structure. Additionally, X-ray diffraction and X-ray fluorescence yield information on parameters describing the bone ultrastructure and elemental composition at the bone-to-implant interface. Finally, with element specific mass spectrometry, the elements and their accumulation in the main organs and tissues are traced. The results show that Mg-xGd implants degrade in vivo under the formation of a stable degradation layer with bone remodeling similar to that of Ti after 10 weeks. No accumulation of Mg and Gd was observed in selected organs, except for the interfacial bone after 8 months of healing. Thus, we confirm that Mg-5Gd and Mg-10Gd are suitable material choices for bone implants.

Sheep Bone Ultrastructure Analyses Reveal Differences in Bone Maturation around Mg-Based and Ti Implants.

Magnesium alloys are some of the most convenient biodegradable materials for bone fracture treatment due to their tailorable degradation rate, biocompatibility, and mechanical properties resembling those of bone. Despite the fact that magnesium-based implants and ZX00 (Mg-0.45Zn-0.45Ca in wt.%), in particular, have been shown to have suitable degradation rates and good osseointegration, knowledge gaps remain in our understanding of the impact of their degradation properties on the bone's ultrastructure. Bone is a hierarchically structured material, where not only the microstructure but also the ultrastructure are important as properties like the local mechanical response are determined by it. This study presents the first comparative analysis of bone ultrastructure parameters with high spatial resolution around ZX00 and Ti implants after 6, 12, and 24 weeks of healing. The mineralization was investigated, revealing a significant decrease in the lattice spacing of the (002) Bragg's peak closer to the ZX00 implant in comparison to Ti, while no significant difference in the crystallite size was observed. The hydroxyapatite platelet thickness and osteon density demonstrated a decrease closer to the ZX00 implant interface. Correlative indentation and strain maps obtained by scanning X-ray diffraction measurements revealed a higher stiffness and faster mechanical adaptation of the bone surrounding Ti implants as compared to the ZX00 ones. Thus, the results suggest the incorporation of Mg2+ ions into the bone ultrastructure, as well as a lower degree of remodeling and stiffness of the bone in the presence of ZX00 implants than Ti.

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.

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.

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.

Severity of Desaturations Reflects OSA-Related Daytime Sleepiness Better Than AHI.

STUDY OBJECTIVES: The aim was to investigate how the severity of apneas, hypopneas, and related desaturations is associated with obstructive sleep apnea (OSA)-related daytime sleepiness. METHODS: Multiple Sleep Latency Tests and polysomnographic recordings of 362 patients with OSA were retrospectively analyzed and novel diagnostic parameters (eg, obstruction severity and desaturation severity), incorporating severity of apneas, hypopneas, and desaturations, were computed. Conventional statistical analysis and multivariate analyses were utilized to investigate connection of apnea-hypopnea index (AHI), oxygen desaturation index (ODI), conventional hypoxemia parameters, and novel diagnostic parameters with mean daytime sleep latency (MSL). RESULTS: In the whole population, 10% increase in values of desaturation severity (risk ratio = 2.01, P < .001), obstruction severity (risk ratio = 2.18, P < .001) and time below 90% saturation (t90%) (risk ratio = 2.05, P < .001) induced significantly higher risk of having mean daytime sleep latency ≤ 5 minutes compared to 10% increase in AHI (risk ratio = 1.63, P < .05). In severe OSA, desaturation severity had significantly (P < .02) stronger negative correlation (ρ = -.489, P < .001) with mean daytime sleep latency compared to AHI (ρ = -.402, P < 0.001) and ODI (ρ = -.393, P < .001). Based on general regression model, desaturation severity and male sex were the most significant factors predicting daytime sleep latency. CONCLUSIONS: Severity of sleep-related breathing cessations and desaturations is a stronger contributor to daytime sleepiness than AHI or ODI and therefore should be included in the diagnostics and severity assessment of OSA. CITATION: Kainulainen S, Töyräs J, Oksenberg A, Korkalainen H, Sefa S, Kulkas A, Leppänen T. Severity of desaturations reflects OSA-related daytime sleepiness better than AHI. J Clin Sleep Med. 2019;15(8):1135-1142.

Does Magnetic Resonance Imaging Provide Superior Reliability for Achilles and Patellar Tendon Cross-Sectional Area Measurements Compared with Ultrasound Imaging?

This study investigated the reliability of Achilles and patellar tendon cross-sectional area (CSA) measurement using ultrasound imaging (USI) and magnetic resonance imaging (MRI). Fifteen healthy adults were imaged twice on two occasions, interrupted by a tendon loading protocol. Tendon CSA segmentations were conducted by an experienced and an inexperienced rater blinded to information regarding subject, session and loading status. USI provided good test-retest reliability (intra-class correlation coefficient [ICC] 2,1 > 0.85, standard error of measurement [SEM] 5%-6%), while with MRI it was excellent (ICC 2,1 > 0.92, SEM 4%) for the experienced rater. This study suggests that MRI provides superior reliability for tendon CSA measurements compared with USI. However, the difference in reliability between the methods was small, and the results were inconclusive regarding objectivity and sensitivity to change when assessed based on the effect of loading. We concluded that both methods can be used for reliable CSA measurements of the Achilles and patellar tendons when using a highly standardized measurement protocol and when conducted by an experienced rater.