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Background Total joint replacements are an established treatment for patients suffering from reduced mobility and pain due to severe joint damage. Aseptic loosening due to stress shielding is currently one of the main reasons for revision surgery. As this phenomenon is related to a mismatch in mechanical properties between implant and bone, stiffness reduction of implants has been of major interest in new implant designs. Facilitated by modern additive manufacturing technologies, the introduction of porosity into implant materials has been shown to enable significant stiffness reduction; however, whether these devices mitigate stress-shielding associated complications or device failure remains poorly understood. Methods In this systematic review, a broad literature search was conducted in six databases (Scopus, Web of Science, Medline, Embase, Compendex, and Inspec) aiming to identify current design approaches to target stress shielding through controlled porous structures. The search keywords included ‘lattice,’ ‘implant,’ ‘additive manufacturing,’ and ‘stress shielding.’ Results After the screening of 2530 articles, a total of 46 studies were included in this review. Studies focusing on hip, knee, and shoulder replacements were found. Three porous design strategies were identified, specifically uniform, graded, and optimized designs. The latter included personalized design approaches targeting stress shielding based on patient-specific data. All studies reported a reduction of stress shielding achieved by the presented design. Conclusion Not all studies used quantitative measures to describe the improvements, and the main stress shielding measures chosen varied between studies. However, due to the nature of the optimization approaches, optimized designs were found to be the most promising. Besides the stiffness reduction, other factors such as mechanical strength can be considered in the design on a patient-specific level. While it was found that controlled porous designs are overall promising to reduce stress shielding, further research and clinical evidence are needed to determine the most superior design approach for total joint replacement implants.

Background Total hip replacement surgery is a well-established intervention that restores joint function and provides excellent outcomes for patients. In some cases, bone resorption caused by stress shielding leads to implant loosening. Stress shielding occurs because implants are much stiffer than bone and transmit a significant proportion of the load, leaving the surrounding bone to carry less load compared to an intact femur. Methods To address stress shielding, we aimed to design patient-specific additively manufactured porous femoral stems with reduced stiffness. Diamond lattice structure test specimens of varying porosities were manufactured and tested to measure elastic moduli and yield strengths. These properties were used in subsequent implant optimisation based on finite element analysis. Four implant templates were created based on the region of the implant that was assigned porous material. These templates were referred to as fully porous (FP), proximally porous with a solid distal end (PP), solid distal shell (DS), and fully solid shell (SS). In addition, the elastic modulus within the porous region was assigned either a linear or a radial distribution, resulting in eight possible implant designs. Results Optimisation yielded six distinct solutions, which were evaluated based on the reduction in stress shielding and micromotion at the bone implant interface. While all implant designs reduced stress shielding compared to a solid implant, only the PP and SS stems were predicted to pass the standard fatigue test for femoral stems (ISO 7206-4). Implant-bone micromotion was conducive for bone implant integration for all designs, with the potential exception of the fully porous stem. Of the implants that were predicted to pass the fatigue test, the linear proximal porous stem resulted in the largest reduction in stress shielding (9.5% for walking, 8.1% for stair climbing). Conclusions Based on patient-specific computational models, the porous region of the stems influenced the reduction of stress shielding compared to fully solid stems. Considering implant fatigue failure and bone-implant micromotion, the PP and SS templates were found to be the most suitable design approaches to address femoral bone stress shielding after total hip replacement. Further investigation is required to fully comprehend the implications of porous femoral stems on long-term implant stability.

The site-dependent load-deformation behavior of the human neurocranium and the load dissipation within the three-layered composite is not well understood. This study mechanically investigated 257 human frontal, temporal, parietal and occipital neurocranial bone samples at an age range of 2 to 94 years, using three-point bending tests. Samples were tested as full-thickness three-layered composites, as well as separated with both diploë attached and removed. Right temporal samples were the thinnest samples of all tested regions (median < 5 mm; p  < 0.001) and withstood lowest failure loads (median < 762 N; p  < 0.001). Outer tables were thicker and showed higher failure loads (median 2.4 mm; median 264 N) than inner tables (median 1.7 mm,  p  < 0.001; median 132 N, p  = 0.003). The presence of diploë attached to outer and inner tables led to a significant reduction in bending strength (with diploë: median < 60 MPa; without diploë: median > 90 MPa, p  < 0.001). Composites (r = 0.243, p  = 0.011) and inner tables with attached diploë (r = 0.214, p  = 0.032) revealed positive correlations between sample thickness and age. The three-layered composite is four times more load-resistant compared to the outer table and eight times more compared to the inner table.

Improved surgical procedures and implant developments for ligament or tendon repair require an in-depth understanding of tissue load-deformation and fatigue properties. Cyclic testing will provide crucial information on the behavior of these materials under reoccurring loads and on fatigue strength. Sparse data are available describing soft tissue behavior under cyclic loading. To examine fatigue strength, a new technology was trialed deploying 3D-printing to facilitate and standardize cyclic tests aiming to determine tendon fatigue behavior. Cadaveric flexor digitorum tendons were harvested and mounted for tensile testing with no tapering being made, using 3D-printed clamps and holder arms, while ensuring a consistent testing length. Loads ranging between 200 to 510 N were applied at a frequency of 4 Hz, and cycles to failure ranged between 8 and >260,000. S–N curves (Woehler curves) were generated based on the peak stresses and cycles to failure. Power regression yielded a combined coefficient of determination of stress and cycles to failure of R2 = 0.65, while the individual coefficients for tissues of single donors ranged between R2 = 0.54 and R2 = 0.88. The here-presented results demonstrate that S–N curves of human tendons can be obtained using a standardized setting deploying 3D-printing technology.

This study assessed the effect of cow milk (CM) and sheep milk (SM) consumption on the micro-structure, mechanical function, and mineral composition of rat femora in a male weanling rat model. Male weanling rats were fed a basal diet with a 50% reduction in calcium and phosphorus content (low Ca/P-diet) supplemented with either SM or CM. Rats were fed for 28 days, after which the femora were harvested and stored. The femora were analyzed by μ-CT, three-point bending, and inductively coupled plasma–mass spectrometry (ICP-MS). The addition of either milk to the low Ca/P-diet significantly increased (p < 0.05) trabecular bone volume, trabecular bone surface density, trabecular number, cortical bone volume, and maximum force, when compared to rats that consumed only the low Ca/P-diet. The consumption of either milk resulted in a significant decrease (p < 0.05) in trabecular pattern factor, and cortical bone surface to volume ratio when compared to rats that consumed only the low Ca/P-diet. The results were achieved with a lower consumption of SM compared to that of CM (p < 0.05). This work indicates that SM and CM can help overcome the effects on bone of a restriction in calcium and phosphorus intake.

Total hip replacement surgery is a well-established intervention that restores joint function and provides excellent outcomes for patients. In some cases, bone resorption caused by stress shielding leads to implant loosening. Stress shielding occurs because implants are much stiffer than bone and transmit a significant proportion of the load, leaving the surrounding bone to carry less load compared to an intact femur. To address stress shielding, we aimed to design patient-specific additively manufactured porous femoral stems with reduced stiffness. Diamond lattice structure test specimens of varying porosities were manufactured and tested to measure elastic moduli and yield strengths. These properties were used in subsequent implant optimisation based on finite element analysis. Four implant templates were created based on the region of the implant that was assigned porous material. These templates were referred to as fully porous (FP), proximally porous with a solid distal end (PP), solid distal shell (DS), and fully solid shell (SS). In addition, the elastic modulus within the porous region was assigned either a linear or a radial distribution, resulting in eight possible implant designs. Optimisation yielded six distinct solutions, which were evaluated based on the reduction in stress shielding and micromotion at the bone implant interface. While all implant designs reduced stress shielding compared to a solid implant, only the PP and SS stems were predicted to pass the standard fatigue test for femoral stems (ISO 7206-4). Implant-bone micromotion was conducive for bone implant integration for all designs, with the potential exception of the fully porous stem. Of the implants that were predicted to pass the fatigue test, the linear proximal porous stem resulted in the largest reduction in stress shielding (9.5% for walking, 8.1% for stair climbing). Based on patient-specific computational models, the porous region of the stems influenced the reduction of stress shielding compared to fully solid stems. Considering implant fatigue failure and bone-implant micromotion, the PP and SS templates were found to be the most suitable design approaches to address femoral bone stress shielding after total hip replacement. Further investigation is required to fully comprehend the implications of porous femoral stems on long-term implant stability.

Total joint replacements are an established treatment for patients suffering from reduced mobility and pain due to severe joint damage. Aseptic loosening due to stress shielding is currently one of the main reasons for revision surgery. As this phenomenon is related to a mismatch in mechanical properties between implant and bone, stiffness reduction of implants has been of major interest in new implant designs. Facilitated by modern additive manufacturing technologies, the introduction of porosity into implant materials has been shown to enable significant stiffness reduction; however, whether these devices mitigate stress-shielding associated complications or device failure remains poorly understood. In this systematic review, a broad literature search was conducted in six databases (Scopus, Web of Science, Medline, Embase, Compendex, and Inspec) aiming to identify current design approaches to target stress shielding through controlled porous structures. The search keywords included 'lattice,' 'implant,' 'additive manufacturing,' and 'stress shielding.' After the screening of 2530 articles, a total of 46 studies were included in this review. Studies focusing on hip, knee, and shoulder replacements were found. Three porous design strategies were identified, specifically uniform, graded, and optimized designs. The latter included personalized design approaches targeting stress shielding based on patient-specific data. All studies reported a reduction of stress shielding achieved by the presented design. Not all studies used quantitative measures to describe the improvements, and the main stress shielding measures chosen varied between studies. However, due to the nature of the optimization approaches, optimized designs were found to be the most promising. Besides the stiffness reduction, other factors such as mechanical strength can be considered in the design on a patient-specific level. While it was found that controlled porous designs are overall promising to reduce stress shielding, further research and clinical evidence are needed to determine the most superior design approach for total joint replacement implants.

Feedback delivery and training have not been characterized in the context of academic cancer centres. The purpose of this study was to assess the feasibility and utility of a microlearning course based on the R2C2 (Relationship, Reaction, Content, Coaching) feedback model and characterize multidisciplinary healthcare provider (HCP) perspectives on existing feedback practices in an academic cancer centre. Five HCP (two radiation oncologists, one medical oncologist, and two allied health professionals) with supervisory roles were selected by purposive sampling to participate in a prospective longitudinal qualitative study. Each participant completed a web-based multimedia course. Semi-structured one-on-one interviews were conducted with each participant at four time points: pre- and immediately post-course, and at one- and three-months post course. All participants found the course to be time feasible and completed it in 10–20 min. Participants expressed that the course fulfilled their need for feedback training and that its adoption may normalize a feedback culture in the cancer centre. Three themes were identified regarding perceptions of existing feedback practices: (1) hierarchical and interdisciplinary relationships modulate feedback delivery, (2) interest in feedback delivery varies by duration of the supervisory relationship, and (3) the transactionality of supervisor-trainee relationships influences feedback delivery. This study demonstrates the perceived feasibility and utility of a digital microlearning approach for development of feedback competencies in an academic cancer centre, perceptions of cultural barriers to feedback delivery, and the need for organizational commitment to developing a feedback culture.

The precise detection of cancer biomarkers is a principal aspect of effective diagnosis, monitoring, and therapeutics. Carcinoembryonic antigen (CEA) is a protein normally found in very small amounts in the blood of adults. CEA blood levels can be elevated in benign diseases and certain types of cancer. The CEA test is most commonly used to identify a significantly frequent cancer, colorectal cancer. It has decisive clinical value in monitoring, differential diagnosis, disease, and assessment of therapeutic effects. Therefore, it is important to develop a sensitive and simple CEA detection method to diagnose cancer and improve patient survival accurately. Biosensing has great advantages for early disease detection due to its rapid response, high sensitivity, and convenient operating characteristics. Based on several studies, biosensors seem to be new and promising paths in the future of medical oncology. The main purpose of this study is to introduce and discuss the recent nanodiagnostic biosensors developed since 2018. Therefore, the readers of this study will be introduced to the latest biosensors, the various nanomaterials used in them, and their analytical characteristics. Graphical abstract

An array-based high-throughput approach termed Escherichia coli synthetic genetic array, or eSGA, now allows comprehensive genetic interaction screens in bacteria. The method makes use of bacterial conjugation and robotic technology to generate double mutants on a genome-wide scale. In this issue, another paper presents GIANT-coli, a very similar approach. Physical and functional interactions define the molecular organization of the cell. Genetic interactions, or epistasis, tend to occur between gene products involved in parallel pathways or interlinked biological processes. High-throughput experimental systems to examine genetic interactions on a genome-wide scale have been devised for Saccharomyces cerevisiae , Schizosaccharomyces pombe , Caenorhabditis elegans and Drosophila melanogaster , but have not been reported previously for prokaryotes. Here we describe the development of a quantitative screening procedure for monitoring bacterial genetic interactions based on conjugation of Escherichia coli deletion or hypomorphic strains to create double mutants on a genome-wide scale. The patterns of synthetic sickness and synthetic lethality (aggravating genetic interactions) we observed for certain double mutant combinations provided information about functional relationships and redundancy between pathways and enabled us to group bacterial gene products into functional modules. NOTE: In the version of this article initially published online two author names (Gabriel Moreno-Hagelseib and Constantine Christopolous) were spelled incorrectly. The correct author names are Gabriel Moreno-Hagelsieb and Constantine Christopoulos. The error has been corrected for the print, PDF and HTML versions of this article.