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In Europe, respiratory protective devices must be certified before they can be marketed. Among the parameters of interest, inward leakage (IL) characterizes the tightness between the face seal and the face, to verify that the device is well-designed. European standard EN 13274-1 (2001) and International Organization for Standardization (ISO) standard ISO 16900-1 (2019) specify that IL should be measured using sodium chloride (NaCl) aerosol or sulfur hexafluoride (SF6) gas. For reusable masks made of nonporous materials, both test agents are considered equally acceptable. However, the few studies that have compared IL values measured with various aerosols and gases have come to divergent conclusions. This work then aimed to measure IL with the test agents recommended by the standards to determine whether they are really equivalent. Since krypton (Kr) is an interesting candidate for replacing SF6 in standard tests, IL was assessed with SF6 and Kr simultaneously, and with NaCl aerosol using various calculation methods. Tests were carried out on 5 models of full-face masks donned on a headform connected to a breathing machine simulating 3 sinusoidal breathing rates of various intensities. The respirator fit on the headform was evaluated using a controlled negative pressure method to determine a manikin fit factor. Four scenarios were then tested to represent very poor, bad, good, and excellent fit. Gas concentration was measured using a mass spectrometer, and IL was calculated for SF6 and Kr. A combination of 3 devices allowed the determination of the number-based concentration of particles with diameters between 20 nm and 2 µm, and IL was calculated for each of the 33 channels, as well as using a cumulative number concentration. In addition, to comply with standards, a conversion was carried out to calculate IL using a cumulative mass concentration. The results of this work evidenced that the IL values measured with NaCl were systematically lower than those determined with gases. IL was also shown to vary with particle size, with a maximum value exceeding that calculated with cumulative concentrations (in number or mass). As part of the revision of the standards, protocols for measuring inward leakage should be redefined. On the one hand, acceptability thresholds should be re-evaluated according to the nature of the test agent (gas or aerosol), as it is clear that the 2 options do not give the same results for a given configuration. On the other hand, the aerosol leakage measurement protocol needs to be reworked to enable the measurement of a well-defined, robust, and reproducible inward leakage value., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Occupational Hygiene Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Research on biomaterials typically starts with cytocompatibility evaluation, using the ISO 10993-5 standard as a reference that relies on extract tests to determine whether the material is safe (cell metabolic activity should exceed 70 %). However, the generalized approach within the standard may not accurately reflect the material's behavior in direct contact with cells, raising concerns about its effectiveness. Calcium phosphates (CaPs) are a group of materials that, despite being highly biocompatible and promoting bone formation, still exhibit inconsistencies in basic cytotoxicity evaluations. Hence, in order to test the cytocompatibility dependence on different experimental setups and material-cell interactions, we used amorphous calcium phosphate, α-tricalcium phosphate, hydroxyapatite, and octacalcium phosphate (0.1 mg/mL to 5 mg/mL) with core cell lines of bone microenvironment: mesenchymal stem cells, osteoblast-like and endothelial cells. All materials have been characterized for their physicochemical properties before and after cellular contact and once in vitro assays were finalized, groups identified as 'cytotoxic' were further analyzed using a modified Annexin V apoptosis assay to accurately determine cell death. The obtained results showed that indirect contact following ISO standards had no sensitivity of tested cells to the materials, but direct contact tests at physiological concentrations revealed decreased metabolic activity and viability. In summary, our findings offer valuable guidelines for handling biomaterials, especially in powder form, to better evaluate their biological properties and avoid false negatives commonly associated with the traditional standard approach., Competing Interests: Declaration of competing interest Authors do not have any conflicts of interest to declare., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Computational modeling and simulation (CM&S) is a key tool in medical device design, development, and regulatory approval. For example, finite element analysis (FEA) is widely used to understand the mechanical integrity and durability of orthopaedic implants. The ASME V&V 40 standard and supporting FDA guidance provide a framework for establishing model credibility, enabling deeper reliance on CM&S throughout the total product lifecycle. Examples of how to apply the principles outlined in the ASME V&V 40 standard are important to facilitating greater adoption by the medical device community, but few published examples are available that demonstrate best practices. Therefore, this paper outlines an end-to-end (E2E) example of the ASME V&V 40 standard applied to an orthopaedic implant. The objective of this study was to illustrate how to establish the credibility of a computational model intended for use as part of regulatory evaluation. In particular, this study focused on whether a design change to a spinal pedicle screw construct (specifically, the addition of a cannulation to an existing non-cannulated pedicle screw) would compromise the rod-screw construct mechanical performance. This question of interest (?OI) was addressed by establishing model credibility requirements according to the ASME V&V 40 standard. Experimental testing to support model validation was performed using spinal rods and non-cannulated pedicle screw constructs made with medical grade titanium (Ti-6Al-4V ELI). FEA replicating the experimental tests was performed by three independent modelers and validated through comparisons of common mechanical properties such as stiffness and yield force. The validated model was then used to simulate F1717 compression-bending testing on the new cannulated pedicle screw design to answer the ?OI, without performing any additional experimental testing. This E2E example provides a realistic scenario for the application of the ASME V&V 40 standard to orthopedic medical device applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

ISO 10993-1:2018 describes evaluating the biocompatibility profile of a medical device from a risk-based approach. This standard details the battery of information that should be considered within the assessment of a device, including raw material composition data, manufacturing processes, and endpoint testing. The ISO 10993/18562 series requires worst-case assumptions and exposure scenarios to be used in the evaluation, which may result in an over-estimation of patient safety risk. Currently, biocompatibility assessments evaluate each data set independently, and the consequence of this individualized assessment of exaggerated inputs is potential false alarms regarding patient safety. To evaluate these safety concerns, the ISO standards indicate that professional judgement should be used to estimate patient risk but does not provide guidance on incorporating a holistic review of the data into the risk assessment. Recalibrating these worst-case data to evaluate them in a weight-of-evidence (WoE) approach may provide a more realistic data set to determine actual patient risk. This proposed WoE framework combines understanding data applicability with a method for gauging the strength of data that can provide additional support for the final safety conclusion. Using a WoE framework will allow risk assessors to contextualize the data and utilize it to comprehensively estimate patient safety., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Biocompatibility testing using in vivo tests is often one of the final evaluations of new dental materials. To reduce the likelihood of failure at this late stage, predictive biocompatibility testing using in vitro methods is needed. In this study, we describe a sensitivity analysis of an oral irritation test by evalu­ating changes in the viability, using the MTT assay, of 3-D models with EpiOral constructs as a case study. Experiments that tested sources of variability in the assay led to recommendations regarding the storage of the constructs after arrival, pipetting procedure, use of MTT reagents from different vendors, use of transepithelial electrical resistance measurements, and statistical analyses. A statis­tical model was proposed to evaluate whether test substances yield a positive or negative result and the associated statistical confidence. Testing several test compounds such as the Y-4 polymer, which contains a known irritant, and dentally relevant substances such as sodium dodecyl sulfate (SDS) at varying concentrations revealed statistically significant results as expected. Lastly, a software app was designed to support a multiwell culture plate layout design. Overall, the findings and sugges­tions documented here will support the further development and potential standardization of this assay system and may be useful for the development of other assays using 3-D constructs.

China is shifting from the stage of large-scale bridge construction to the stage of equal emphasis on the construction and maintenance of bridges. The problems of low efficiency and high cost in bridge inspection are becoming more and more prominent, which threaten people's life safety. In this paper, the deterioration state prediction model of concrete beam bridge under Boosting DT C5.0 was established as the basis, and optimization suggestions were put forward in terms of bridge inspection standards and processes, which aims to perfect the bridge inspection mechanism, realize the fine management of the bridge and prolong the service life of the bridge. Research shows that: first, the bridge inspection standard with a single index should be improved into the bridge inspection standard with multiple indexes, so as to scientifically determine the bridges that need to be inspected and optimize the allocation of maintenance resources. Second, the bridge deterioration state prediction model is used to add a screening mechanism for the bridge in the inspection plan, which can effectively reduce the workload of bridge inspection and enhance the inspection efficiency. Third, the deterioration phenomenon of coexistence between adjacent traffic assets should be fully considered and the linkage inspection mechanism of adjacent traffic assets should be established to improve the effect of bridge inspection., Competing Interests: The authors have declared that no competing interests exist.

The COVID-19 pandemic has caused a high demand for respiratory protection among health care workers in hospitals, especially surgical N95 filtering facepiece respirators (FFRs). To aid in alleviating that demand, a survey of commercially available filter media was conducted to determine whether any could serve as a substitute for an N95 FFR while held in a 3D-printed mask (Stopgap Surgical Face Mask from the NIH 3D Print Exchange). Fourteen filter media types and eight combinations were evaluated for filtration efficiency, breathing resistance (pressure drop), and liquid penetration. Additional testing was conducted to evaluate two filter media disinfection methods in the event that the filters were reused in a hospital setting. Efficiency testing was conducted in accordance with the procedures established for approving an N95 FFR. One apparatus used a filter-holding device and another apparatus employed a manikin head to which the 3D-printed mask could be sealed. The filter media and combinations exhibited collection efficiencies varied between 3.9% and 98.8% when tested with a face velocity comparable to that of a standard N95 FFR at the 85 L min -1 used in the approval procedure. Breathing resistance varied between 10.8 to >637 Pa (1.1 to > 65 mm H 2 O). When applied to the 3D-printed mask efficiency decreased by an average of 13% and breathing resistance increased 4-fold as a result of the smaller surface area of the filter media when held in that mask compared to that of an N95 FFR. Disinfection by dry heat, even after 25 cycles, did not significantly affect filter efficiency and reduced viral infectivity by > 99.9%. However, 10 cycles of 59% vaporized H 2 O 2 significantly (p < 0.001) reduced filter efficiency of the media tested. Several commercially available filter media were found to be potential replacements for the media used to construct the typical cup-like N95 FFR. However, their use in the 3D-printed mask demonstrated reduced efficiency and increased breathing resistance at 85 L min -1 .

This study aimed to analyze fracture strength in vitro by varying the axial height of the titanium insert and the labial height of the zirconia abutment in an internal connection implant to identify the titanium insert axial height with optimal mechanical stability. Sixty implants with an internal connection system were used. Two-piece zirconia abutments were used with the titanium inserts. Combinations of different titanium insert axial heights (mm) and zirconia abutment labial heights (mm) constituted five groups: Gr1 (1-3), Gr2 (3-3), Gr3 (3-5), Gr4 (5-3), and Gr5 (5-5). After thermocycling, a fracture load test was performed with a universal testing machine. The initial deformation load and the fracture load were measured and analyzed. The fractured surface and cross-section of the specimens were examined by scanning electron microscopy (SEM). The groups of titanium inserts with axial heights of 3 mm and 5 mm showed significantly greater initial deformation load and fracture load than the group with an axial height of 1 mm (p < 0.05), but there was no significant difference between the two groups with axial heights of 3 mm and 5 mm. The labial height of the zirconia abutment had no significant influence on the initial deformation load and fracture load. In some specimens in Gr4 and Gr5, cracking or bending of the titanium insert and abutment screw was observed on SEM. The axial height of the titanium insert should be designed to not be less than 3 mm to increase the fracture strength and promote the long-term stability of implants., Competing Interests: The authors have declared that no competing interests exist.

The SARS-CoV-2 global pandemic has produced widespread shortages of certified air-filtering personal protection equipment and an acute need for rapid evaluation of breathability and filtration efficiency of proposed alternative solutions. Here, we describe experimental efforts to nondestructively quantify three vital characteristics of mask approaches: breathability, material filtration effectiveness, and sensitivity to fit. We focus on protection against aqueous aerosols >0.3 μm using off-the-shelf particle, flow, and pressure sensors, permitting rapid comparative evaluation of these three properties. We present and discuss both the pressure drop and the particle penetration as a function of flow to permit comparison of relative protection for a set of proposed filter and mask designs. The design considerations of the testing apparatus can be reproduced by university laboratories and medical facilities and used for rapid local quality control of respirator masks that are of uncertified origin, monitoring the long-term effects of various disinfection schemes and evaluating improvised products not designed or marketed for filtration.

In this study, the hemocompatibility of tubes with an inner diameter of 5 mm made of polyvinyl chloride (PVC) and coated with different bioactive conjugates was compared to uncoated PVC tubes, latex tubes, and a stent for intravascular application that was placed inside the PVC tubes. Evaluation of hemocompatibility was done using an in vitro hemodynamic loop model that is recommended by the ISO standard 10993-4. The tubes were cut into segments of identical length and closed to form loops avoiding any gap at the splice, then filled with human blood and rotated in a water bath at 37 °C for 3 hours. Thereafter, the blood inside the tubes was collected for the analysis of whole blood cell count, hemolysis (free plasma hemoglobin), complement system (sC5b-9), coagulation system (fibrinopeptide A), and leukocyte activation (polymorphonuclear elastase, tumor necrosis factor and interleukin-6). Host cell activation was determined for platelet activation, leukocyte integrin status and monocyte platelet aggregates using flow cytometry. The effect of inaccurate loop closure was examined with x-ray microtomography and scanning electron microscopy, that showed thrombus formation at the splice. Latex tubes showed the strongest activation of both plasma and cellular components of the blood, indicating a poor hemocompatibility, followed by the stent group and uncoated PVC tubes. The coated PVC tubes did not show a significant decrease in platelet activation status, but showed an increased in complement and coagulation cascade compared to uncoated PVC tubes. The loop model itself did not lead to the activation of cells or soluble factors, and the hemolysis level was low. Therefore, the presented in vitro hemodynamic loop model avoids excessive activation of blood components by mechanical forces and serves as a method to investigate in vitro interactions between donor blood and vascular medical devices.

Recently, several spinal exoskeletons were developed with the aim to assist occupational tasks such as load-handling and work in prolonged static postures. While the biomechanical effects of such devices has been well investigated, only limited feedback to the developers is usually provided regarding the subjective perceptions of the end-users. The aim of this study was to present a novel battery of tests, designed to assess functional performance and subjective outcomes during the use of assistive trunk exoskeletons, and to assess its test-retest reliability. The battery of tests consists of 12 different simple functional tasks. Twenty participants were included in an intra-session reliability test and repeated the tests within 7-10 days to assess inter-session reliability. They were wearing a novel passive spinal exoskeleton during all trials. The outcomes included quantitative and subjective measures, such as performance time and rating of discomfort and perceived task difficulty. The majority of the outcome measures were reliable within session and between sessions (ICC or α > 0.80). Systematic effects were observed in a few tasks, suggesting that familiarization trials will be needed to minimize the learning effects. The novel battery of tests could become an important easy-to-use tool for functional testing of the spinal exoskeletons in addition to more specific biomechanical and physiological testing. Further studies should address the reliability of the present battery of tests for assessing specific populations, such as low back pain patients and explore how to minimize systematic effects that were observed in this study., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Elemental impurities in drug products arise from different sources and via a number of different means, including leaching of elemental entities (including the elements themselves or element-containing compounds) from the drug product's manufacturing or packaging systems. Thus, knowledge about the presence, level, and likelihood of leaching of elements in manufacturing and packaging systems is relevant to understanding how these systems contribute to a drug product's total elemental impurity burden. To that end, this manuscript updates a previous review of available literature on elemental entities in pharmaceutically relevant polymers and the presence of these elemental entities in material extracts and/or drug products. This updated review contains the information that has been published subsequent to the publication of the initial review and considers two questions: (1) What elemental entities are present in the relevant polymers and materials and at what levels are they present? (2) To what extent are these elemental entities leached from these materials under conditions relevant to the manufacturing and storage/distribution of solution drug products? The compiled recent data reaffirms the conclusions drawn from the original review: (1) Elemental entities are present in the materials used to construct packaging and manufacturing systems as these materials either contain these elemental entities as additives or are exposed to the elemental entities during their production. (2) Unless the elemental entities were parts of the materials themselves (e.g., SiO 2 in glass) or intentionally added to the materials (e.g., metal stearates in polymers), their incidental amounts in the materials were generally low. (3) If elemental entities were present in materials and systems, generally only a very small fraction of the total available amount of the entity could be leached under conditions that were relevant to the packaged drug products. Thus, although sources of certain elemental impurities may be ubiquitous in the natural environment, they were not ubiquitous in materials used in pharmaceutical packaging and manufacturing systems and when they were present, they were not extensively leached under relevant conditions of use for those systems. This conclusion, supported by an ever-increasing body of literature, suggests that in general the manufacturing and packaging systems, by themselves, do not contribute sufficiently large quantities of elemental impurities that the impurities pose a meaningful threat to patient safety. Furthermore, this conclusion should be considered when standards are developed for the characterization and qualification of manufacturing systems, packaging systems, and their associated materials and components of construction., (© PDA, Inc. 2020.)

A drug delivery system is designed to administer a therapeutic dose according to its label claim. Upon delivery of a parenteral drug product, the volume remaining inside the container that cannot be extracted at the end of drug administration is called the hold-up volume (HUV) and is primarily considered product wastage. To meet the label claim, every drug product container is filled with a slight excess volume. For early-stage products in clinical phase, for which material availability is often a limitation, excess volume in drug product containers has to be determined experimentally using several grams of product. In such scenarios, established models that can predict HUV in primary drug product containers would be valuable for product development. The objective of this study was to determine HUV with 95% confidence intervals across various container closures and drug delivery systems by using aqueous PEG 400 solution mimicking the viscosity of biologic drug products. ISO 2R, 6R, and 10R vials and single-use hypodermic syringes attached to a Luer lock needle (25 gauge, 1½ in.) were used to mimic parenteral drug product container and delivery systems for determination of HUV. Glass prefilled syringes in 1 mL and 2.25 mL configurations were also used to determine HUV with 95% confidence intervals. A linear regression model was developed for determination of HUV as a function of viscosity and as a function of container closure and a needle-based delivery system. This model predicting HUV was confirmed by using monoclonal antibodies of varying formulations and viscosities for container closure and delivery systems tested in this study. The model provided here can be used to determine HUV for a particular container closure for a drug solution with known viscosity that can subsequently be used to evaluate fill volume specifications and label claim for a dosage form., (© PDA, Inc. 2020.)

A vial-capping process for lyophilization stopper configurations was previously quantified using residual seal force (RSF). A correlation between RSF and container closure integrity (CCI) was established, and component positional offsets were identified to be the primary source of variability in RSF measurements.To gain insight into the effects of stopper geometry on CCI, serum stoppers with the same rubber formulation were investigated in this study. Unlike lyophilization stoppers that passed CCI (per helium leak testing) even with RSF of 0 N owing to their excellent valve seal, serum stoppers consistently failed CCI when RSF was <15.8 N. When the plug was removed, both types of stoppers exhibited a comparable critical lower RSF limit (19-20 N), below which CCI could not be maintained. When CCI was retested at later time points (up to 6 mo), some previously failed vials passed CCI, suggesting that CCI improvement might be related to rubber relaxation (viscous flow), which can fill minor imperfections on the vial finish.To confirm component positional offsets are the primary sources of RSF variability, a novel quantification tool-micro-computed tomography (micro-CT)-was used in this study. Micro-CT provided images for quantification of positional offsets of the cap and stopper that directly correlated with RSF fluctuations. Serum stoppers and lyophilization stoppers are comparable in RSF variations, although lyophilization stoppers are more robust in CCI. The use of micro-CT provides a nondestructive and innovative tool in quantitatively analyzing component features of capped vials that would otherwise be difficult to investigate., (© PDA, Inc. 2020.)

Glass is the favorite material for parenteral packaging because of its physico-chemical properties. Type I borosilicate glass is worldwide use at this scope, but it may have some issues related to breakage, corrosion and delamination that might compromise the drug quality, safety and efficacy. These issues can be mitigated and avoided starting from the appropriate selection of the most suitable raw material at the early stage of the glass container design. In this study, Type I borosilicate glass vials manufactured using two glass tubes having different chemical compositions, were studied and compared in terms of their resistance to corrosion. Testing design was applied with the aim to select the best practice approach comparing different storage simulation conditions: ageing treatment through autoclaving and stability testing (real-time and accelerated). Clear differences were found between the different glass types in terms of hydrolytic and corrosion resistance that highlighted the relation between chemical composition and glass chemical durability. Non-negligible differences were also observed using different storage conditions., (© PDA, Inc. 2020.)

Background: Additively manufactured porous metallic structures have recently received great attention for bone implant applications. The morphological characteristics and mechanical behavior of 3D printed titanium alloy trabecular structure will affect the effects of artificial prosthesis replacement. However, the mechanical behavior of titanium alloy trabecular structure at present clinical usage still is lack of in-depth study from design to manufacture as well as from structure to mechanical function., Methods: A unit cell of titanium alloy was designed to mimick trabecular structure. The controlled microarchitecture refers to a repeating array of unit-cells, composed of titanium alloy, which make up the scaffold structure. Five kinds of unit cell mimicking trabecular structure with different pore sizes and porosity were obtained by modifying the strut sizes of the cell and scaling the cell as a whole. The titanium alloy trabecular structure was fabricated by 3D printing based on Electron Beam Melting (EBM). The paper characterized the difference between the designs and fabrication of trabecular structures, as well as mechanical properties and the progressive collapse behavior and failure mechanism of the scaffold., Results: The actual porosities of the EBM-produced bone trabeculae are lower than the designed, and the load capacity of a bearing is related to the porosity of the structure. The larger the porosity of the structure, the smaller the stiffness and the worse the load capacity is. The fracture interface of the trabecular structure under compression is at an angle of 45 o with respect to the compressive axis direction, which conforms to Tresca yield criterion. The trabeculae-mimicked unit cell is anisotropy. Under quasi-static loading, loading speed has no effect on mechanical performance of bone trabecular specimens. There is no difference of the mechanical performance at various orientations and sites in metallic workspace. The elastic modulus of the scaffold decreases by 96%-93% and strength reduction 96%-91%, compared with titanium alloy dense metals structure. The apparent elastic modulus of the unit-cell-repeated scaffold is 0.39-0.618 GPa, which is close to that of natural bone and stress shielding can be reduced., Conclusion: We have systematically studied the structural design, fabrication and mechanical behavior of a 3D printed titanium alloy scaffold mimicking trabecula bone. This study will be benefit of the application of prostheses with proper structures and functions.

Objective: Despite immense popularity of Jaipur foot as low cost prosthetic, not much work has been reported on its design for manufacturing standardization. Without manufacturing standardization, it cannot be mass produced using contemporary manufacturing technologies. The objective of this work is to carry out its computer aided design (CAD) followed by computer aided engineering (CAE) based on the material properties obtained from the previous work [1] of the authors. This may lead to the possible use of modern manufacturing processes for the Jaipur foot design. Design: After modelling using CAD tool including its organic surfaces, the designed foot was analysed using a CAE tool for balanced standing load conditions to determine maximum stresses and deformation in its various parts. The bending analysis was done to check the dorsiflexion movement so that the strained sections could be identified for more reliable and durable prosthetic foot. For the static load analysis, base of the foot was constrained and 300-500 N load was applied through the bolt whereas for bending, the part near the bolt was fixed and pressure was applied at junction of front foot and toes. Results: The results show that the maximum stress and deformation occur at the bolt, while the skin undergoes maximum strain. CAE analysis also proves the robustness of the Jaipur foot design and a well manufactured Jaipur foot as per standardized design should be able to withstand the real life conditions without failure. The CAD model is also used for FDM based printing for a nonfunctional prototype of Jaipur foot.Implications for rehabilitationThe results of this study will serve as an important guideline for further research regarding equivalent material replacement, material optimization and obtaining an optimized design after studying the foot for dynamic analysis.

Mechanical testing machines used in cadaveric spine biomechanics research vary between labs. It is a necessary first step to understand the capabilities and limitations in any testing machine prior to publishing experimental data. In this study, a reproducible protocol that uses a synthetic spine was developed and used to quantify the inherent rotation error and the ability to apply loads in a single physiologic plane (pure-moment) of a custom spine biomechanics simulator. Rotation error was evaluated by comparing data collected by the test machine and the data collected by an optical motion capture system. Pure-moment loading was assessed by comparing the out-of-plane loads to the primary plane load. Using synthetic functional spine units previously shown to have mechanics similar to the cadaveric human spine, the simulator was evaluated using a dynamic test protocol reflective of its future use in the study of cadaveric spine specimens. Rotation errors inherent in the test machine were <0.25° compared to motion capture. Out of plane loads were <4.0% of the primary plane load, which confirmed pure-moment loading. The authors suggest that a standard validation protocol for biomechanical spine testing machines is needed for transparency and accurate field-wide data interpretation and comparison. We offer recommendations based on the reproducible use of a synthetic spinal specimen for consideration., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

A model was developed that can be used to predict how hydrogen peroxide (H 2 O 2 ) transfers into a liquid drug product that is exposed to vapor phase hydrogen peroxide (VPHP). This model accounts for fluid flow in both the gas and liquid phases as well as the diffusion and convection mechanisms of mass transfer using the first principles of engineering to predict the amount of H 2 O 2 that will transfer from the gas to the liquid phase considering a given geometrical system and surrounding conditions. The model was used to investigate how much space is needed in a given container to eliminate convective mass transfer and to create a balance between mass transfer and the air/liquid interface for oxidation-sensitive products in cartridges or vials being filled in an isolator. Experimental results compared well with model predictions. A no-slip boundary condition between the gas and liquid phases was used for the model, which was especially important for the full syringes where convective mass transport predominated. This model may be used to evaluate isolator designs for filling oxidation-sensitive products utilizing the correlation between spiking studies and VPHP uptake to minimize the uptake studies required. It could also be used to inform the design of containers that would minimize the potential for VPHP uptake. For the geometry tested here, it was demonstrated that convection only occurs near the top few millimeters of the container. If the fill level is lower, as it would be for a syringe, the diffusion mechanism of transfer predominates and the rate of transfer of H 2 O 2 is much slower. The balance between mass transfer by convection and diffusion should be a consideration in the design of the system to be filled., (© PDA, Inc. 2020.)

There has been a growing interest in the assessment of container closure systems (CCS) for cold storage and shipment. Prior publications have lacked systematic considerations for the impact of dynamic time temperature transition on sealing performance associated with the viscoelastic characteristics of rubber stoppers used in container closure systems (CCSs). This paper demonstrates that sealing performance changes inherently and is fundamentally both time- and temperature-dependent. Our research results display this critical time temperature transition impact on CCS sealing performance by applying compression stress relaxation (CSR) on a rubber stopper for experimental data collection and modeling evaluation. The experimental results agree with modeling evaluation following Maxwell-Wiechert theory and the time temperature superposition based on the Arrhenius and Williams-Landel-Ferry methods. Both testing and modeling data show good consistency, demonstrating that the sealing force inevitably changes over time together with temperature transition because of the viscoelastic nature of the rubber stoppers. Our results show that compression seal force decreases quickly as temperature decreases. The significant loss of rubber stopper sealing force at lower temperature transitions could contribute significant risk to CCI at low storage and transport temperatures. Modeling evaluation, with a powerful capability to handle actual testing data, can be employed as a predictive tool to evaluate the time- and temperature-dependent sealing force throughout the entire sealed drug product life span. The present study is only applicable before reaching the rubber glass transition temperature Tg - a critical transition phase that can not be skipped/separated from real time temperature transition, and it will further determine the CCS sealing performance while approaching cryogenic temperature. The present work provides a new, integrated methodology framework and some fresh insights to the parenteral packaging industry for practically and proactively considering, designing, setting up, controlling, and managing stopper sealing performance throughout the entire sealed drug product life span., (© PDA, Inc. 2020.)

Background: More elderly patients are suffering from intertrochanteric fractures. However, the choice of internal fixation is still controversial, especially in the treatment of unstable intertrochanteric fracture; thus, previous implants continue to be improved, and new ones are being developed. The purpose of our study was to compare the biomechanical advantages between the zimmer natural nail (ZNN) and proximal femoral nail antirotation-II (PFNA-II) in the treatment of elderly reverse obliquity intertrochanteric fractures., Methods: A three-dimensional finite element was applied for reverse obliquity intertrochanteric fracture models (AO31-A3.1) fixed with the ZNN or PFNA-II. The distribution, peak value and position of the von Mises stress and the displacement were the criteria for comparison between the two groups., Results: The stresses of the internal fixation and femur in the ZNN model were smaller than those in the PFNA-II model, and the peak values of the two groups were 364.8 MPa and 171.8 MPa (ZNN) and 832.3 MPa and 1795.0 MPa (PFNA-II). The maximum amount of displacement of the two groups was similar, and their locations were the same, i.e., in the femoral head vertex (3.768 mm in the ZNN model and 3.713 mm in the PFNA-II model)., Conclusions: The displacement in the two models was similar, but the stresses in the implant and bone were reduced with the ZNN. Therefore, the ZNN implant may provide biomechanical advantages over PFNA-II in reverse obliquity intertrochanteric fractures, as shown through the finite element analysis. These findings from our study may provide a reference for the perioperative selection of internal fixations.

Skin exposure to chemicals in the workplace environment is a major concern, the hands being the major exposure sites. Employers purchase gloves that have permeation data generated from permeation "standards" of the American Society for Testing and Materials International (ASTM International), European Committee for Standardization (EN), and the International Organization for Standardization (ISO) that test pieces of glove material and allow a user-defined temperature. The relevant standards based on continuous contact are ASTM F739, ASTM D6978, EN 374, EN 16523, and ISO 6529. The aim was to analyze the current state of the scientific literature on glove permeation in the 21 st century up to December 2018. The introduction sets out the background, objectives and rationale of the review and its methodology followed by presentation of basic glove chemical resistance terms and Fick's first law of diffusion, the details of the major permeation standards, their comparison, their critique, their research gaps; the scientific literature on whole glove permeation, and final conclusions. The major recommendation was to harmonize all the permeation standards and perform them at realistic work conditions, especially temperature. The whole glove system would be most useful for testing the thinnest gloves.

The use of bone-filling material to repair bone defects and fix implanted bone grafts is a developing area in medicine. Investigators can evaluate bone-filling materials through use of several indices to make comparisons and to determine suitability for application in humans 1 . However, it is quite difficult to transform their discovery into practical use, because the viability of the studied material might require examination of all aspects of properties. In addition, for a material to become a product, a complete procedure involving a declaration, registration, and approval is necessary. This article introduces the technical indices that the investigators and reporters should provide in their declaration and registration data to meet the relevant standards in China. The indices include physical and chemical properties, biocompatibility, biosecurity, pre-clinical animal model tests, sterilization and disinfection, product duration, and packaging. Full consideration of all possible indices is crucial to realize the transformation from a designed product to a commercial medical device, which requires effective interaction between clinicians and engineers., (© 2019 The Authors. Orthopaedic Surgery published by Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.)

Introduction: The advanced design techniques used in modern prosthetic heart valve (PHV) development require accurate replication of the entire cardiac cycle. While cardiac pulse duplicator (CPD) design has a direct impact on the PHV test data generated, no clear guidelines exist to evaluate the CPD's performance. In response to this, we present a method to quantitatively assess CPD performance., Materials and Methods: A method to establish the fidelity of CPDs was formulated based on the pressure/time relationship and the error related to this relationship's target. This method was applied to assess the performance of a custom-made CPD. The performance evaluation included the assessment of the motion control system and overall repeatability of pressure measurements using a St Jude Epic 21 mm aortic valve., Results: The CPD's motion control system had an average root mean square error (RMSE) beat-to-beat tracking accuracy of 0.046 ± 0.008 mm. Assessment of the pressure measurements yielded a repeatability of < 2.4 ± 0.9 mmHg RMSE beat-to-beat differential pressure. The combination of pressure and its location within a heartbeat (fidelity) was within 5.0% of the individual targets for at least 95% of heartbeats., Conclusion: Fidelity can be used to objectively quantify the performance of various aspects of CPDs and to identify the cause of unexpected PHV or CPD behaviour. It also enables comparisons to be made among various CPDs in terms of overall performance. This approach may enable standardization of the assessment of CPD performance in the future.

Playgrounds surface test standards have been introduced to reduce the number of fatal and severe injuries. However, these test standards have several simplifications to make it practical, robust and cost-effective, such as the head is represented with a hemisphere, only the linear kinematics is evaluated and the body is excluded. Little is known about how these simplifications may influence the test results. The objective of this study was to evaluate the effect of these simplifications on global head kinematics and head injury prediction for different age groups. The finite element human body model PIPER was used and scaled to seven different age groups from 1.5 up to 18 years old, and each model was impacted at three different playground surface stiffness and three head impact locations. All simulations were performed in pairs, including and excluding the body. Linear kinematics and skull bone stress showed small influence if excluding the body while head angular kinematics and brain tissue strain were underestimated by the same simplification. The predicted performance of the three different playground surface materials, in terms of head angular kinematics and brain tissue strain, was also altered when including the body. A body and biofidelic neck need to be included, together with suitable head angular kinematics based injury thresholds, in future physical or virtual playground surface test standards to better prevent brain injuries., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Purpose: International Standards Organization (ISO) 12189 and American Society for Testing and Materials F2624 are two standard material specification and test methods for spinal implant devices. The aim of this study was to assess whether the existing and required tests before market launch are sufficient., Methods: In three prospective studies, patients were treated due to degenerative disease of the lumbar spine or spondylolisthesis with lumbar interbody fusion and dynamic stabilization of the cranial adjacent level. The CD HORIZON BalanC rod and S 4 Dynamic rod were implanted in 45 and 11 patients, respectively., Results: A fatigue fracture of the material of the topping off system has been found in five cases (11%) for the group fitted with the CD HORIZON BalanC rod. In the group using the S 4 Dynamic rod group, a material failure of the dynamic part was demonstrated in seven patients (64%). All three studies were interrupted due to these results, and a report to the Federal Institute for Drugs and Medical Devices was generated., Conclusion: Spinal implants have to be checked by a notified body before market launch. The notified body verifies whether the implants fulfil the requirements of the current standards. These declared studies suggest that the current standards for the testing of load bearing capacity and stand ability of dynamic spine implants might be insufficient. Revised standards depicting sufficient deformation and load pattern have to be developed and counted as a requirement for the market launch of an implant. These slides can be retrieved under Electronic Supplementary Material.

Medical devices comprise a wide variety of therapeutic tools aimed at modulating or restoring organ function. Devices may be implanted or activated temporally or permanently, and are used to deliver a wide range of therapies such as drugs, electrical stimulation, laser, thermal energy, offer mechanical support, and restore sensory functions. Technological advancements allow improvement and development of devices at a rapid pace. This special issue of Toxicologic Pathology addresses a need for more publications focused on pathology evaluation of medical devices in preclinical studies and highlights fundamental approaches through practical examples bringing into perspective the essential role of pathologists in this field.

The development of biomaterials, medical device components, finished medical products, and 3-D printed and regenerative medicine products is governed by a variety of international and country-specific standards and guidelines. Of greatest importance to planning, executing, and reporting biocompatibility, safety and efficacy studies for most biomaterials and medical components or products are the International Organization for Standardization guidelines, U.S. Pharmacopeial Convention, ASTM International, and Conformité Européenne (European Conformity) marking. The International Medical Device Regulators Forum publishes harmonized standards similar to the International Council for Harmonization. Good Laboratory Practices are applicable and guidance documents for the development of drugs and biologics can also be relevant to biomaterials, medical device components, and medical products and more recently to products produced by 3-D printing or additive manufacturing. Regenerative products may have medical device-based scaffolding and may be treated as biologics, reflecting the cell and tissue components. This compilation of international standards and guidelines provides toxicologic pathologists, toxicologists, bioengineers, and allied professionals with an overview of and source for important regulatory documents that may apply to the nonclinical development of their products.

Histology of medical devices poses a variety of unique challenges. Comprehensive histologic assessment of medical devices often requires spatial context and high-quality retention of the device-tissue interface. However, the composition of many medical devices is often not amenable to traditional paraffin embedding and thus alternative specialized methodologies such as hard resin embedding must be used. Hard resin embedding requires specialized laboratory technical expertise and equipment, and the fixation techniques and resin composition used markedly impact the feasibility of immunohistochemistry. For the continuity of spatial context during histologic evaluation, additional imaging methods such as macrophotography, radiography, micro-Computerized Tomography (microCT), or magnetic resonance imaging (MRI) can be used to guide sectioning and to complement histologic findings. Although standardized approaches are scarce for medical devices, important considerations specific to medical device histology are discussed, including general specimen preparation, special considerations for devices by organ system, and the challenges of immunohistochemistry. Histologic preparation of medical devices must be thoughtful, thorough, and tailored to achieve optimal histologic outcomes for complex, valuable, and often limited implant specimens.

Background: This study was conducted to measure the effect of different drilling depths on compression forces generated by two commonly used headless compression screws using the two different types of drill bit, the Acutrak® mini (conical type drill bit) and the Synthes 3.0 HCS® (cylindrical type drill bit)., Methods: A load cell was placed between two Sawbone blocks, which were 12 mm and 40 mm in thickness, respectively. After placing the guide pin into the center of the block, the drilling depth of the Acutrak® mini and Synthes HCS® screws ranged from 16 to 28 mm and 22 to 28 mm, respectively. The 24-mm screws were inserted and the compression force was measured immediately and at 30 min post-insertion., Results: The Acutrak® mini generated greater compression force compared to the Synthes 3.0 HCS® when drilled to a depth of less than 24 mm. The compression force of the Acutrak® mini showed a strong inverse correlation with the drilling depth. There was no significant inverse correlation observed between the compression force of the Synthes HCS® and the drilling depth., Conclusions: If the screw length and the drill depth are the same, the Synthes 3.0 HCS® (cylindrical type drill bit) is safer and easier to use as it has no change in the compression force even when over-drilling because the compression force of the two screws is similar. As for the Acutrak® mini (conical type drill bit), while it is technically demanding due to varying compression force according to the drill depth, it can be used in certain cases because it can give stronger compression force through under-drilling.

Background: This study aimed to explore the effect of retaining inferomedial cortical bone contact and fixation with calcar screws on the dynamic and static mechanical stability of proximal humerus fractures treated with a locking plate., Methods: Twelve Synbone prosthetic humeri (SYNBONE-AG, Switzerland) were used for a wedge osteotomy model at the proximal humerus, in four groups. In the cortex contact + screw fixation group and cortex contact group, the inferomedial cortical bone contact was retained. In the screw fixation group and control group, the inferomedial cortical bone contact was not retained. Calcar screw fixation was implemented only in the screw fixation groups. The dynamic and static mechanical stability of the models were tested with dynamic fatigue mechanics testing, quasi-static axial compression, three-point bending, and torsion testing., Results: The cortex contact + screw fixation group showed the longest fatigue life and the best stability. There was 35% difference in fatigue life between the cortex contact + screw fixation group and the cortex contact group, 43%between the cortex contact + screw fixation group and screw fixation group, and 63% between the cortex contact + screw fixation group and screw fixation group (P < 0.01). The cortex contact + screw fixation group showed the best axial compressive stiffness, bending stiffness, and torsion stiffness; these were successively decreased in the other three groups (P < 0.01)., Conclusion: Retaining inferomedial cortical bone contact and fixation with two calcar screws maintained fracture stability with the highest strength and minimum deformation. Of the two methods, restoration of the inferomedial cortical bone support showed better dynamic and static biomechanical properties than placement of calcar screws alone.

Purpose: A credible computational fluid dynamics (CFD) model can play a meaningful role in evaluating the safety and performance of medical devices. A key step towards establishing model credibility is to first validate CFD models with benchmark experimental datasets to minimize model-form errors before applying the credibility assessment process to more complex medical devices. However, validation studies to establish benchmark datasets can be cost prohibitive and difficult to perform. The goal of this initiative sponsored by the U.S. Food and Drug Administration is to generate validation data for a simplified centrifugal pump that mimics blood flow characteristics commonly observed in ventricular assist devices., Methods: The centrifugal blood pump model was made from clear acrylic and included an impeller, with four equally spaced, straight blades, supported by mechanical bearings. Particle Image Velocimetry (PIV) measurements were performed at several locations throughout the pump by three independent laboratories. A standard protocol was developed for the experiments to ensure that the flow conditions were comparable and to minimize systematic errors during PIV image acquisition and processing. Velocity fields were extracted at the pump entrance, blade passage area, back gap region, and at the outlet diffuser regions. A Newtonian blood analog fluid composed of sodium iodide, glycerin, and water was used as the working fluid. Velocity measurements were made for six different pump flow conditions, with the blood-equivalent flow rate ranging between 2.5 and 7 L/min for pump speeds of 2500 and 3500 rpm., Results: Mean intra- and inter-laboratory variabilities in velocity were ~ 10% at the majority of the measurement locations inside the pump. However, the inter-laboratory variability increased to more than ~ 30% in the exit diffuser region. The variability between the three laboratories for the peak velocity magnitude in the diffuser region ranged from 5 to 25%. The bulk velocity field near the impeller changed proportionally with the rotational speed but was relatively unaffected by the pump flow rate. In contrast, flow in the exit diffuser region was sensitive to both the flow rate and the rotational speed. Specifically, at 3500 rpm, the exit jet tilted toward the inner wall of the diffuser at a flow rate of 2.5 L/min, but the jet tilted towards the outer wall when the flow rate was 7 L/min., Conclusions: Inter-laboratory experimental mean velocity data (and the corresponding variance) were obtained for the FDA pump model and are available for download at https://nciphub.org/wiki/FDA&#95;CFD . Experimental datasets from the inter-laboratory characterization of benchmark flow models, including the blood pump model presented herein and our previous nozzle model, can be used for validating future CFD studies and to collaboratively develop guidelines on best practices for verification, validation, uncertainty quantification, and credibility assessment of CFD simulations in the evaluation of medical devices (e.g. ASME V&V 40 standards working group).

The governing international standard for the development of prosthetic heart valves is International Organization for Standardization (ISO) 5840. This standard requires the assessment of the thrombus potential of transcatheter heart valve substitutes using an integrated thrombus evaluation. Besides experimental flow field assessment and ex vivo flow testing, computational fluid dynamics is a critical component of this integrated approach. This position paper is intended to provide and discuss best practices for the setup of a computational model, numerical solving, post-processing, data evaluation and reporting, as it relates to transcatheter heart valve substitutes. This paper is not intended to be a review of current computational technology; instead, it represents the position of the ISO working group consisting of experts from academia and industry with regards to considerations for computational fluid dynamic assessment of transcatheter heart valve substitutes.

Transcatheter Mitral Valve Replacement (TMVR) is currently under clinical investigation as a viable treatment option for mitral regurgitation (MR). Therefore, it is important to outline the key functional requirements of a TMVR prosthesis in order to provide an overall approach to assessing mitral valve replacement devices utilizing a combination of in vitro and preclinical methods. This article provides a review of the mitral valve disease as well as general considerations and guidance for developing a TMVR device based on International Industry Standards. Specific details pertaining to the mitral valve apparatus, morphology of mitral valve disease, assessment of specific patient population as well as hazard analysis to evaluate and develop a TMVR device to treat a specific patient population have been included. The details contained within this report are not all inclusive or explicate for every technology being developed but rather thought of as a general guide on how a TMVR technology could be developed in alignment with International Industry Standards. Key learnings from the Transcatheter Aortic Valve Replacement (TAVR) experience has also been considered and taken into account when outlining this general guidance for TMVR. Key learning points from the TAVR development experience included the following: quantification of acceptable levels of paravalvular leak, valve migration potential using various anchoring methods and overall implant frame failure modes when treating the native aortic valve. It should be noted that TAVR is over a decade further along in development and clinical experience compared to TMVR. These key learnings from the early experience with TAVR should be considered with all transcatheter development projects.

Experimental flow field characterization is a critical component of the assessment of the hemolytic and thrombogenic potential of heart valve substitutes, thus it is important to identify best practices for these experimental techniques. This paper presents a brief review of commonly used flow assessment techniques such as Particle image velocimetry (PIV), Laser doppler velocimetry, and Phase contrast magnetic resonance imaging and a comparison of these methodologies. In particular, recommendations for setting up planar PIV experiments such as recommended imaging instrumentation, acquisition and data processing are discussed in the context of heart valve flows. Multiple metrics such as residence time, local velocity and shear stress that have been identified in the literature as being relevant to hemolysis and thrombosis in heart valves are discussed. Additionally, a framework for uncertainty analysis and data reporting for PIV studies of heart valves is presented in this paper. It is anticipated that this paper will provide useful information for heart valve device manufacturers and researchers to assess heart valve flow fields for the potential for hemolysis and thrombosis.

Study Design: A cadaveric biomechanical study designed to test the pullout strength of pedicle screws., Objective: To evaluate the pullout strength of redirected pedicle screws with a larger diameter following lateral wall breach, redirected pedicle screws of the same diameter following medial wall breach, and redirected pedicle screws with a larger diameter following medial wall breach., Summary of Background Data: Screw malposition is one of the main pitfalls of inserting pedicle screws. Intraoperatively a malpositioned screw is redirected and inserted along the correct axis., Methods: Forty-seven vertebrae (T9-L5) were harvested from eight fresh cadaveric spines. The 18 pedicle screws that breached the lateral wall were then removed and redirected using a pedicle screw of 1 mm larger in diameter. The 16 pedicle screws that had breached the medial wall were then removed and redirected using a pedicle screw of the same diameter. The other 13 pedicle screws that had breached the medial wall were then removed and redirected using a pedicle screw of 1 mm larger in diameter. The pullout strength was measured., Results: Following lateral wall breach, mean pullout strength for the larger redirected screws was 46.9% greater than that of the correctly aligned screws. Following medial wall breach, mean pullout strength for the redirected screws of the same diameter was 20.6% less than that of the correctly aligned screws. Mean pullout strength for the larger pedicle screws following medial wall breach was 27.3% more than that of the correctly aligned screws., Conclusion: Redirected pedicle screws of larger diameter after a lateral or medial pedicle breach show recovery of pullout strength. However, the pullout strength of redirected pedicle screws of the same diameter after a medial pedicle breach is significantly less than that of correctly aligned screws., Level of Evidence: 1.

Background: Hyaluronidase is a hyaluronic acid (HA) metabolizing enzyme, which is approved as an adjuvant for infiltration anesthesia. The "off-label" use of hyaluronidase is regarded as gold standard for the management of HA-filler-associated complications. Yet, up to date there are only few studies that have systematically assessed the degradability of different HA-fillers by hyaluronidase., Objective: To analyze the interactions of HA-fillers and hyaluronidase in a time-dependent manner using a novel standardized in vitro approach., Methods: Comparable HA-fillers, Belotero Balance Lidocaine (BEL; Merz), Emervel classic (EMV; Galderma) and Juvederm Ultra 3 (JUV; Allergan), were incubated with a fluorescent dye and bovine hyaluronidase (HYAL; Hylase "Dessau", Riemser) or control (NaCl) and monitored by time-lapse videomicroscopy. The degradation of HA-fillers was assessed as decrease in fluorescence intensity of HA-filler plus hyaluronidase vs. HA-filler plus control, quantified by computer-assisted image analysis (ImageJ)., Results: Hyaluronidase showed a significant degradation of the HA-fillers BEL and EMV. Degradation was measurable at 5 h (BEL) and 7 h (EMV), respectively; significance was reached at 14 h (BEL) and 13 h (EMV). No effect of hyaluronidase was observed for JUV., Conclusion: Time-lapse microscopy enables systematically, standardized, comparative in vitro analyses of the interactions of hyaluronidase and HA-fillers.

Purpose: Ballistic gelatin is commonly used as a validated surrogate for soft tissue during terminal ballistic testing. However, the effect of a delay between production and testing of a gelatin mould remains unknown. The aim of this study was to determine any potential effects of ageing on ballistic gelatin., Methods: Depth of penetration (DoP) of 4.5 mm spherical fragment simulating projectiles was ascertained using mixtures of 10%, 11.25% and 20% Type A 250 Bloom ballistic gelatin. Testing was performed daily for 5 days using velocities between 75 and 210 m/s. DoP at day 5 was statistically compared with day 1, and net mass change was recorded daily., Results: No significant difference was found for DoP observed with time in any of the samples (P>0.05). Spearman correlation was excellent in all moulds. The moulds with known standard calibrations remained in calibration throughout the study period. Mass loss of less than 1% was noted in all samples., Conclusion: Mass loss was the only quantifiable measure of changes in the blocks with time, but did not correlate with any changes in DoP. This may provide reassurance when undertaking such testing that an inadvertent delay will not significantly alter the penetration properties of the mould. Future research is recommended to determine any potential effect on the mechanical properties of gelatin at higher velocity impacts and whether the calibration corresponds to an adequate simulation under such conditions., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

The majority of orthopaedic screws are designed, tested and manufactured by existing orthopaedics companies and are predominantly developed with healthy bone in mind. The timescales and costs involved in the development of a new screw design, for example, for osteoporotic bone, are high. In this study, standard wood screws were used to analyse the concept of using three-dimensional printing, or rapid prototyping, as a viable stage of development in the design of a new bone screw. Six wood screws were reverse engineered and printed in polymeric material using stereolithography. Three of the designs were also printed in Ti6Al4V using direct metal laser sintering; however, these were not of sufficient quality to test further. Both the original metal screws (metal) and polymeric rapid prototyping screws were then tested using standard pull-out tests from low-density polyurethane blocks (Sawbones). Results showed the highest pull-out strengths for screws with the longest thread length and the smallest inner diameter. Of the six screw designs tested, five showed no more than a 17% variance between the metal and rapid prototyping results. A similar pattern of results was shown between the screw designs for both the metal and rapid prototyping screws in five of the six cases. While not producing fully comparable pull-out results to orthopaedic screws, the results from this study do provide evidence of the potential usefulness and cost-effectiveness of rapid prototyping in the early stages of design and testing of orthopaedic screws.

The moisture from skin sweat and atmospheric water affects the thermal protective performance provided by multilayer protective clothing. Four levels of moisture content were selected to evaluate the impact of moisture on thermal protection under dry (thermal radiation) and wet (thermal radiation and low-pressure steam) heat exposure. Also, the role of moisture and its relationship with exposure time were analyzed based on skin heat flux and Henriques integral value. The addition of moisture to a fabric system was found to result in differences in second-degree and third-degree skin burn times. When moisture is added to a fabric system, it both acts as a thermal conductor to present a negative effect and provides a positive effect owing to thermal storage of water and evaporative heat loss. The positive or negative effects of moisture are mainly dependent on the thermal exposure time, the moisture content and the presence of hot steam.

This review intends to present a comprehensive analysis of the mechanical considerations for chronically-implanted neural probes. Failure of neural electrical recordings or stimulation over time has shown to arise from foreign body reaction and device material stability. It seems that devices that match most closely with the mechanical properties of the brain would be more likely to reduce the mechanical stress at the probe/tissue interface, thus improving body acceptance. The use of low Young's modulus polymers instead of hard substrates is one way to enhance this mechanical mimetism, though compliance can be achieved through a variety of means. The reduction of probe width and thickness in comparison to a designated length, the use of soft hydrogel coatings and the release in device tethering to the skull, can also improve device compliance. Paradoxically, the more compliant the device, the more likely it will fail during the insertion process in the brain. Strategies have multiplied this past decade to offer partial or temporary stiffness to the device to overcome this buckling effect. A detailed description of the probe insertion mechanisms is provided to analyze potential sources of implantation failure and the need for a mechanically-enhancing structure. This leads us to present an overview of the strategies that have been put in place over the last ten years to overcome buckling issues. Particularly, great emphasis is put on bioresorbable polymers and their assessment for neural applications. Finally, a discussion is provided on some of the key features for the design of mechanically-reliable, polymer-based next generation of chronic neuroprosthetic devices.

Safety ("biocompatibility") assessment of medical devices has evolved along a different path than that of drugs, being historically governed more by the considerations and needs of engineers rather than chemists and biologists. As a result, the involvement of veterinary pathologists has been much more limited-almost entirely to evaluating tissue responses in tissues in direct contact with implanted devices. As devices have become more complex in composition, structure, placement, and use, concerns as to adverse systemic responses in patients have called for more comprehensive and thoughtful evaluations of effects throughout the body. Further complexities arise from the increasing marriage of devices and drug/biologic therapeutics to achieve either better dose control and, specifically, in delivery to target organs/tissues or better tolerance of the body to medical devices (i.e., minimization of the foreign body response). The challenge to pathologists is to integrate in new technologies (such as in vivo imaging and immunology) and ways of viewing interactions with patient bodies. To fail to do so will allow the methods and standards for medical device safety evaluation to be based on chemical analysis and then the limited details inherent in literature-based risk assessments.

Friction is the natural response of all tribosystems. In a total knee replacement (TKR) prosthetic device, its measurement is hindered by the complex geometry of its integrating parts and that of the testing simulation rig operating under the ISO 14243-3:2014 standard. To develop prediction models of the coefficient of friction (COF) between AISI 316L steel and ultra-high molecular weight polyethylene (UHMWPE) lubricated with fetal bovine serum dilutions, the arthrokinematics and loading conditions prescribed by the ISO 142433: 2014 standard were translated to a simpler geometrical setup, via Hertz contact theory. Tribological testing proceeded by loading a stainless steel AISI 316L ball against the surface of a UHMWPE disk, with the test fluid at 37 °C. The method has been applied to study the behavior of the COF during a whole walking cycle. On the other hand, the role of protein aggregation phenomena as a lubrication mechanism has been extensively studied in hip joint replacements but little explored for the operating conditions of a TKR. Lubricant testing fluids were prepared with fetal bovine serum (FBS) dilutions having protein mass concentrations of 5, 10, 20 and 36 g/L. The results were contrasted against deionized, sterilized water. The results indicate that even at protein concentration as low as 5 g/L, protein aggregation phenomena play an important role in the lubrication of the metal-on-polymer tribopair. The regression models of the COF developed herein are available for numerical simulations of the tribological behavior of the aforementioned tribosystem. In this case, surface stress rather than film thickness should be considered., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Current treatment for end-stage osteoarthritis is total knee replacement. Given that the number of total knee replacement surgeries is expected to approach 3.48 million by 2030, understanding long-term failure is important. One of the preclinical tests for total knee replacements is carried out using mechanical wear testing under generic walking conditions. Used for this purpose is the International Standards Organization's generic walking profile. Recently this standard was updated by reversing the direction of anterior/posterior translation and internal/external rotation. The effects of this change have not been investigated, and therefore, it is unknown if comparisons between wear tests utilizing the old and new version of the standard are valid. In this study, we used a finite element model along with a frictional energy-based wear model to compare the kinematic inputs, contact conditions, and wear from the older and newer versions of the ISO standard. Simulator-tested components were used to validate the computational model. We found that there were no visible similarities in the contact conditions between the old and new versions of the standard. The new version of the standard had a lower wear rate but covered a larger portion of the articular surface. Locations of wear also varied considerably. The results of the study suggest that major differences between the old and new standard exist, and therefore, historical wear results should be compared with caution to newly obtained results.

Background: This biomechanical study evaluates the effect of N-acetylcysteine alone and in combination with the most commonly used antibiotic-loaded bone cement mixtures., Methods: We mixed eight bone cement mixture groups including combinations of N-acetylcysteine, gentamicin, teicoplanin, and vancomycin and applied a four-point bending test individually to each sample on days 1 and 15 using an MTS Acumen test device., Results: The result was less than 50 MPa-the limit declared by the ISO (International Standards Organization)-in only the "gentamicin + bone cement + N-acetylcysteine" group. Mechanical fatigue resistance of the bone cement decreased significantly with the addition of N-acetylcysteine both on day 1 and day 15 (p <  0.001). With the addition of N-acetylcysteine into the "gentamicin + bone cement" and "vancomycin + bone cement" mixtures, a significant decrease in mechanical fatigue resistance was observed both on day 1 and day 15 (p <  0.001). In contrast, with the addition of N-acetylcysteine into the "teicoplanin + bone cement" mixture, no significant difference in mechanical fatigue resistance was observed on days 1 and 15 (p = 0.093, p = 0.356)., Conclusion: Preliminary results indicate that adding N-acetylcysteine to teicoplanin-loaded bone cement does not significantly affect the cement's mechanical resistance, potentially leading to a new avenue for preventing and treating peri-prosthetic joint infection. N-acetylcysteine may, therefore, be considered as an alternative agent to be added to antibiotic-loaded bone cement mixtures used in the prevention of peri-prosthetic joint infection.

This review paper shows that tungsten should not generally be used as a chronically implanted material. The metal has a long implant history, from neuroscience, vascular medicine, radiography, orthopaedics, prosthodontics, and various other fields, primarily as a result of its high density, radiopacity, tensile strength, and yield point. However, a crucial material criterion for chronically implanted metals is their long-term resistance to corrosion in body fluids, either by inherently noble metallic surfaces, or by protective passivation layers of metal oxide. The latter is often assumed for elemental tungsten, with references to its 'inertness' and 'stability' common in the literature. This review argues that in the body, metallic tungsten fails this criterion, and will eventually dissolve into the soluble hexavalent form W 6+ , typically represented by the orthotungstate [Formula: see text] (monomeric tungstate) anion. This paper outlines the metal's unfavourable corrosion thermodynamics in the human physiological environment, the chemical pathways to either metallic or metal oxide dissolution, the rate-limiting steps, and the corrosion-accelerating effects of reactive oxidising species that the immune system produces post-implantation. Multiple examples of implant corrosion have been reported, with failure by dissolution to varying extents up to total loss, with associated emission of tungstate ions and elevated blood serum levels measured. The possible toxicity of these corrosion products has also been explored. As the field of medical implants grows and designers explore novel solutions to medical implant problems, the authors recommend the use of alternative materials.

This is a consensus document from the European Bifurcation Club concerning bench testing in coronary artery bifurcations. It is intended to provide guidelines for bench assessment of stents and other strategies in coronary bifurcation treatment where the United States Food and Drug Administration (FDA) or International Organization for Standardization (ISO) guidelines are limited or absent. These recommendations provide guidelines rather than a step-by-step manual. We provide data on the anatomy of bifurcations and elastic response of coronary arteries to aid model construction. We discuss testing apparatus, bench testing endpoints and bifurcation nomenclature.