Establishing finite element model credibility of a pedicle screw system under compression-bending: An end-to-end example of the ASME V&V 40 standard.

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.

Reproducibility in modeling and simulation of the knee: Academic, industry, and regulatory perspectives.

Stakeholders in the modeling and simulation (M&S) community organized a workshop at the 2019 Annual Meeting of the Orthopaedic Research Society (ORS) entitled "Reproducibility in Modeling and Simulation of the Knee: Academic, Industry, and Regulatory Perspectives." The goal was to discuss efforts among these stakeholders to address irreproducibility in M&S focusing on the knee joint. An academic representative from a leading orthopedic hospital in the United States described a multi-institutional, open effort funded by the National Institutes of Health to assess model reproducibility in computational knee biomechanics. A regulatory representative from the United States Food and Drug Administration indicated the necessity of standards for reproducibility to increase utility of M&S in the regulatory setting. An industry representative from a major orthopedic implant company emphasized improving reproducibility by addressing indeterminacy in personalized modeling through sensitivity analyses, thereby enhancing preclinical evaluation of joint replacement technology. Thought leaders in the M&S community stressed the importance of data sharing to minimize duplication of efforts. A survey comprised 103 attendees revealed strong support for the workshop and for increasing emphasis on computational modeling at future ORS meetings. Nearly all survey respondents (97%) considered reproducibility to be an important issue. Almost half of respondents (45%) tried and failed to reproduce the work of others. Two-thirds of respondents (67%) declared that individual laboratories are most responsible for ensuring reproducible research whereas 44% thought that journals are most responsible. Thought leaders and survey respondents emphasized that computational models must be reproducible and credible to advance knee M&S.

The relative influence of model parameters on finite element analysis simulations of intervertebral body fusion device static compression performance.

Non-clinical mechanical performance testing is a critical aspect of intervertebral body fusion device (IBFD) development and regulatory evaluation. Recently, stakeholders have begun leveraging computational modeling and simulations such as finite element analysis (FEA) in addition to traditional bench testing. FEA offers advantages such as reduced experiment time, lower costs associated with elimination of bench testing (e.g. specimen manufacture and test execution), and elucidating quantities of interest that traditional testing cannot provide (e.g. stress and strain distributions). However, best practices for FEA of IBFDs are not well defined, and modeler decision making can significantly influence simulation setup and results. Therefore, the goal of this study was to determine the relative influence of modeling parameters when using FEA to assess non-clinical mechanical performance of IBFDs. FEA was used to conduct a series of IBFD static uniaxial compression simulations. Several parameters relating to implant geometry, loading/boundary conditions, and material properties were carefully controlled to assess their relative influence on two output variables (IBFD stiffness and yield load). Results were most influenced by device geometry, while the effects of boundary conditions and material properties were more significant within IBFDs of identical or similar geometries. These results will aid stakeholders in the development of standardized best practices for using FEA to assess non-clinical mechanical performance of IBFDs.

A Validated Open-Source Shoulder Finite Element Model and Investigation of the Effect of Analysis Precision.

Understanding the loads and stresses on different tissues within the shoulder complex is crucial for preventing joint injury and developing shoulder implants. Finite element (FE) models of the shoulder joint can be helpful in describing these forces and the biomechanics of the joint. Currently, there are no validated FE models of the intact shoulder available in the public domain. This study aimed to develop and validate a shoulder FE model, then make the model available to the orthopaedic research community. Publicly available medical images of the Visible Human Project male subject's right shoulder were used to generate the model geometry. Material properties from the literature were applied to the different tissues. The model simulated abduction in the scapular plane. Simulated glenohumeral (GH) contact force was compared to in vivo data from the literature, then further compared to other in vitro experimental studies. Output variable results were within one standard deviation of the mean in vivo experimental values of the GH contact force in 0°, 10°, 20°, 30°, and 45° of abduction. Furthermore, a comparison among different analysis precision in the Abaqus/Explicit platform was made. The complete shoulder model is available for download at github.com/OSEL-DAM/ShoulderFiniteElementModel.

Assessing the use of finite element analysis for mechanical performance evaluation of intervertebral body fusion devices.

BACKGROUND: Intervertebral body fusion devices (IBFDs) are a widely used type of spinal implant placed between two vertebral bodies to stabilize the spine for fusion in the treatment of spinal pathologies. Assessing mechanical performance of these devices is critical during the design, verification, and regulatory evaluation phases of development. While traditionally evaluated with physical bench testing, empirical assessments are at times supplemented with computational models and simulations such as finite element analysis (FEA). However, unlike many mechanical bench tests, FEA lacks standardized practices and consistency of implementation. OBJECTIVES: The objectives of this study were twofold. First, to identify IBFD 510(k) submissions containing FEA and conduct a comprehensive review of the elements provided in the FEA reports. Second, to engage with spinal device manufacturers through an anonymous survey and assess their practices for implementing FEA. METHODS: First, a retrospective analysis of 510(k) submissions for IBFDs cleared by the FDA between 2013 and 2017 was performed. The contents of FEA test reports were quantified according to FDA guidance. Second, a survey inquiring about the use of FEA was distributed to industry and academic stakeholders. The survey asked up to 20 questions relating to modeler experience and modeling practices. RESULTS: Significant gaps were present in model test reports that deemed the data unreliable and, therefore, unusable for regulatory decision-making in a high percentage of submissions. Nonetheless, the industry survey revealed most stakeholders employ FEA during device evaluation and are interested in more prescriptive guidelines for executing IBFD models. CONCLUSIONS: This study showed that while inconsistencies and gaps in FEA execution do exist within the spinal device community, the stakeholders are eager to work together in developing standardized approaches for executing computational models to support mechanical performance assessment of spinal devices in regulatory submissions.

An ex vivo model of medical device-mediated bacterial skin translocation.

The skin is a barrier and part of the immune system that protects us from harmful bacteria. Because indwelling medical devices break this barrier, they greatly increase the risk of infection by microbial pathogens. To study how these infections can be prevented through improved clinical practices and medical device technology, it is important to have preclinical models that replicate the early stages of microbial contamination, ingress, and colonization leading up to infection. At present, there are no preclinical ex vivo models specifically developed to simulate conditions for indwelling medical devices. Translocation of pathogens from outside the body across broken skin to normally sterile internal compartments is a rate-limiting step in infectious pathogenesis. In this work, we report a sensitive and reproducible ex vivo porcine skin-catheter model to test how long antimicrobial interventions can delay translocation. Skin preparation was first optimized to minimize tissue damage. The presence of skin dramatically decreased bacterial migration time across the polyurethane catheter interface from > 96 h to 12 h. Using visual colony detection, fluorescence, a luminescent in vitro imaging system, and confocal microscopy, the model was used to quantify time-dependent differences in translocation for eluting and non-eluting antimicrobial catheters. The results show the importance of including tissue in preclinical biofilm models and help to explain current gaps between in vitro testing and clinical outcomes for antimicrobial devices.

FDA public workshop: Orthopaedic sensing, measuring, and advanced reporting technology (SMART) devices.

Traditional orthopaedic devices do not communicate with physicians or patients post-operatively. After implantation, follow-up of traditional orthopaedic devices is generally limited to episodic monitoring. However, the orthopaedic community may be shifting towards incorporation of smart technology. Smart technology in orthopaedics is a term that encompasses a wide range of potential applications. Smart orthopaedic implants offer the possibility of gathering data and exchanging it with an external reader. They incorporate technology that enables automated sensing, measuring, processing, and reporting of patient or device parameters at or near the implant. While including advanced technology in orthopaedic devices has the potential to benefit patients, physicians, and the scientific community, it may also increase the patient risks associated with the implants. Understanding the benefit-risk profile of new smart orthopaedic devices is critical to ensuring their safety and effectiveness. The 2018 FDA public workshop on orthopaedic sensing, measuring, and advanced reporting technology (SMART) devices was held on April 30, 2018, at the FDA White Oak Campus in Silver Spring, MD with the goal of fostering a collaborative dialogue amongst the orthopaedic community. Workshop attendees discussed four key areas related to smart orthopaedic devices: engineering and technology considerations, clinical and patient perspectives, cybersecurity, and regulatory considerations. The workshop presentations and associated discussions highlighted the need for the orthopaedic community to collectively craft a responsible path for incorporating smart technology in musculoskeletal disease care.

Characterizing loads at transfemoral osseointegrated implants.

Establishing normative and outlying loads on transfemoral osseointegrated devices will assist development of preclinical mechanical testing strategies to inform manufacturers and government regulators. Therefore, force and moment data from osseointegrated transfemoral transcutaneous implants were collated to better understand baseline load levels. Load data were also collected from other devices including transfemoral socket prostheses, instrumented hip stems, instrumented knee devices, instrumented limb salvage femoral endoprostheses, as well as estimated loads on transfemoral prostheses using data from able-bodied subjects. These additional data were assessed for their ability to bolster the limited osseointegrated device data. Several activities of daily living were investigated to characterize normative loading. Falling events were investigated to characterize outlying loads. Results revealed that limited loading data exist for osseointegrated devices. The most often reported activity was level walking. While these normative data may inform fatigue testing, they may not fully characterize fatigue loads during all activities of daily living. Socket prosthetics and able-bodied individuals may provide supplementary data, but significance is limited by sample sizes. Falling data are sparse, and insufficient data exist for characterizing adverse loads on osseointegrated devices. Future data collection should include more activities of daily living and adverse events to better define osseointegrated device loading profiles.

Specimen-Specific Finite Element Models for Predicting Fretting Wear in Total Hip Arthroplasty Tapers.

Products from fretting wear and corrosion in the taper junction of total hip arthroplasty (THA) devices can lead to adverse local tissue reactions. Predicting damage as a function of design parameters would aid in the development of more robust devices. The objectives of this study were to develop an automated method for identifying areas of fretting wear on THA taper junctions, and to assess the predictive ability of a finite element model to simulate fretting wear in THA taper junctions. THA constructs were fatigue loaded, thus inducing damage on the stem taper. An automated imaging and analysis algorithm quantified fretting wear on the taper surfaces. Specimen-specific finite element models were used to calculate fretting work done (FWD) at the taper junction. Simulated FWD was correlated to imaged fretting wear. Results showed that the automated imaging approach identified fretting wear on the taper surface. Additionally, finite element models showed the greatest predictive ability for tapers exhibiting distal contact. Finite element models predicted an average of 30.3% of imaged fretting wear. With additional validation, the imaging and finite element techniques may be useful to manufacturers and regulators in the development and review of new THA devices.

The fracture toughness of small animal cortical bone measured using arc-shaped tension specimens: Effects of bisphosphonate and deproteinization treatments.

Small animal models, and especially transgenic models, have become widespread in the study of bone mechanobiology and metabolic bone disease, but test methods for measuring fracture toughness on multiple replicates or at multiple locations within a single small animal bone are lacking. Therefore, the objective of this study was to develop a method to measure cortical bone fracture toughness in multiple specimens and locations along the diaphysis of small animal bones. Arc-shaped tension specimens were prepared from the mid-diaphysis of rabbit ulnae and loaded to failure to measure the radial fracture toughness in multiple replicates per bone. The test specimen dimensions, crack length, and maximum load met requirements for measuring the plane strain fracture toughness. Experimental groups included a control group, bisphosphonate treatment group, and an ex vivo deproteinization treatment following bisphosphonate treatment (5 rabbits/group and 15 specimens/group). The fracture toughness of ulnar cortical bone from rabbits treated with zoledronic acid for six months exhibited no difference compared with the control group. Partially deproteinized specimens exhibited significantly lower fracture toughness compared with both the control and bisphosphonate treatment groups. The deproteinization treatment increased tissue mineral density (TMD) and resulted in a negative linear correlation between the measured fracture toughness and TMD. Fracture toughness measurements were repeatable with a coefficient of variation of 12-16% within experimental groups. Retrospective power analysis of the control and deproteinization treatment groups indicated a minimum detectable difference of 0.1MPa·m1/2. Therefore, the overall results of this study suggest that arc-shaped tension specimens offer an advantageous new method for measuring the fracture toughness in small animal bones.

The sensitivity of nonlinear computational models of trabecular bone to tissue level constitutive model.

Microarchitectural finite element models have become a key tool in the analysis of trabecular bone. Robust, accurate, and validated constitutive models would enhance confidence in predictive applications of these models and in their usefulness as accurate assays of tissue properties. Human trabecular bone specimens from the femoral neck (n = 3), greater trochanter (n = 6), and lumbar vertebra (n = 1) of eight different donors were scanned by µ-CT and converted to voxel-based finite element models. Unconfined uniaxial compression and shear loading were simulated for each of three different constitutive models: a principal strain-based model, Drucker-Lode, and Drucker-Prager. The latter was applied with both infinitesimal and finite kinematics. Apparent yield strains exhibited minimal dependence on the constitutive model, differing by at most 16.1%, with the kinematic formulation being influential in compression loading. At the tissue level, the quantities and locations of yielded tissue were insensitive to the constitutive model, with the exception of the Drucker-Lode model, suggesting that correlation of microdamage with computational models does not improve the ability to discriminate between constitutive laws. Taken together, it is unlikely that a tissue constitutive model can be fully validated from apparent-level experiments alone, as the calculations are too insensitive to identify differences in the outcomes. Rather, any asymmetric criterion with a valid yield surface will likely be suitable for most trabecular bone models.

Development of an in vivo rabbit ulnar loading model.

Ulnar and tibial cyclic compression in rats and mice have become the preferred animal models for investigating the effects of mechanical loading on bone modeling/remodeling. Unlike rodents, rabbits provide a larger bone volume and normally exhibit intracortical Haversian remodeling, which may be advantageous for investigating mechanobiology and pharmaceutical interventions in cortical bone. Therefore, the objective of this study was to develop and validate an in vivo rabbit ulnar loading model. Ulnar tissue strains during loading of intact forelimbs were characterized and calibrated to applied loads using strain gauge measurements and specimen-specific finite element models. Periosteal bone formation in response to varying strain levels was measured by dynamic histomorphometry at the location of maximum strain in the ulnar diaphysis. Ulnae loaded at 3000 microstrain did not exhibit periosteal bone formation greater than the contralateral controls. Ulnae loaded at 3500, 4000, and 4500 microstrain exhibited a dose-dependent increase in periosteal mineralizing surface (MS/BS) compared with contralateral controls during the second week of loading. Ulnae loaded at 4500 microstrain exhibited the most robust response with significantly increased MS/BS at multiple time points extending at least 2weeks after loading was ceased. Ulnae loaded at 5250 microstrain exhibited significant woven bone formation. Rabbits required greater strain levels to produce lamellar and woven bone on periosteal surfaces compared with rats and mice, perhaps due to lower basal levels of MS/BS. In summary, bone adaptation during rabbit ulnar loading was tightly controlled and may provide a translatable model for human bone biology in preclinical investigations of metabolic bone disease and pharmacological treatments.

Fatigue microcracks that initiate fracture are located near elevated intracortical porosity but not elevated mineralization.

In vivo microcracks in cortical bone are typically observed within more highly mineralized interstitial tissue, but postmortem investigations are inherently limited to cracks that did not lead to fracture which may be misleading with respect to understanding fracture mechanisms. We hypothesized that the one fatigue microcrack which initiates fracture is located spatially adjacent to elevated intracortical porosity but not elevated mineralization. Therefore, the spatial correlation between intracortical porosity, elevated mineralization, and fatigue microdamage was investigated by combining, for the first time, sequential, nondestructive, three-dimensional micro-computed tomography (micro-CT) measurements of each in cortical bone specimens subjected to compressive fatigue loading followed by a tensile overload to fracture. Fatigue loading resulted in significant microdamage accumulation and compromised mechanical properties upon tensile overload compared to control specimens. The microdamage that initiated fracture upon tensile overload was able to be identified in all fatigue-loaded specimens using contrast-enhanced micro-CT and registered images. Two-point (or pair) correlation functions revealed a spatial correlation between microdamage at the fracture initiation site and intracortical porosity, but not highly mineralized tissue, confirming the hypothesis. This difference was unique to the fracture initiation site. Intracortical porosity and highly mineralized tissue exhibited a significantly lower and higher probability, respectively, of being located spatially adjacent to all sites of microdamage compared to the fracture initiation site. Therefore, the results of this study suggest that human cortical bone is tolerant of most microcracks, which are generally compartmentalized within the more highly mineralized interstitial tissue, but a single microcrack of sufficient size located in spatial proximity to intracortical porosity can compromise fracture resistance.

The relative influence of apatite crystal orientations and intracortical porosity on the elastic anisotropy of human cortical bone.

Elastic anisotropy exhibits spatial inhomogeneity in human cortical bone, but the structural origins of anatomic variation are not well understood. In this study, the elastic anisotropy of human cortical bone was predicted using a specimen-specific multiscale model that investigated the relative influence of apatite crystal orientations and intracortical porosity. The elastic anisotropy of cortical bone specimens from the diaphysis of human femora was measured by ultrasonic wave propagation as the ratio of elastic constants in the longitudinal/radial (L/R) and longitudinal/circumferential (L/C) anatomic specimen axes. Experimental measurements of elastic constants exhibited orthotropy, with greater anisotropy in the L/R plane compared to the L/C plane. Model predictions included (1) a micromechanical model accounting for the effects of apatite crystal orientations, (2) a voxel-based finite element model accounting for the effects of intracortical porosity, and (3) a combined model accounting for both effects. The combined model provided the most accurate predictions of elastic anisotropy in both the L/R and L/C plane, with less than 10% mean error. The micromechanical model alone was able to accurately predict elastic anisotropy in the L/C plane, but predicted transverse isotropy. The finite element model alone grossly underestimated elastic anisotropy in both the L/R and L/C planes, but was able to predict orthotropy. Therefore, the results of this study suggest that the dominant and less variable transverse isotropy of human cortical bone, reflected by L/C, is governed primarily by apatite crystal orientations, while the more subtle and variable orthotropy, reflected by the difference between L/R and L/C, is governed primarily by intracortical porosity. Moreover, the combined model may be useful to investigate other structure-function relationships or in place of current numerical models, for example, in the study of bone adaptation and metabolic bone disease.