Search

Background and Objective: The use of in silico clinical trials (ISCTs) to generate clinically-relevant data on new medical devices is an emerging area of regulatory research. Interest in ISCTs stems from recognized challenges in acquiring sufficient clinical data and the continued maturation of in silico technologies. There is currently no guidance in place for evaluating the credibility of ISCT applications. The objective of this work was to adapt an existing risk-based credibility framework specifically for ISCT applications, and demonstrate its utility on a contemporary case study., Methods: Expanding on guidance currently in place for assessing the risk of traditional modeling applications of medical devices and demonstrating model credibility through benchtop validation activities, a framework is proposed to (1) evaluate the model risk for ISCT applications based on the independent factors of scope, coverage, and severity, and (2) assess the credibility of clinical validation activities based on consideration of the clinical comparator, the validation model, the agreement between the two, and the applicability of the clinical validation activities to the ISCT application., Results: The resulting framework spans across the range of ISCT applications that may be envisioned, as well as the variety of clinical datasets that can be used to demonstrate model credibility. Credibility factors reflect the expected clinical variability in the validation comparator and validation model, the statistical power of the comparator, the rigor of agreement between the comparator and model in terms of both inputs and outputs, and the overall similarity of the device in the validation activities to the device within the intended ISCT. When applied to a high-risk case study, the framework reveals that planned clinical validation activities require additional rigor in order to achieve the credibility targets, enabling an assessment of the validation effort relative to the potential benefit prior to investing in the validation studies., Discussion: An objective and risk-based framework for establishing credibility requirements for ISCT applications is a critical step in advancing ISCT from theory to practice. The proposed framework enforces that appropriate validation of ISCT applications requires evidence that the intended clinical environment is accurately represented. The framework will contribute to reducing uncertainty amongst technical, clinical, and regulatory constituents on ISCT applications, and promote rational adoption., Competing Interests: Declaration of Competing Interest Jeff Bischoff, Mehul Dharia, and Philippe Favre are employees of Zimmer Biomet., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Revision rates in total ankle arthroplasty (TAA) are nearly double compared with hip or knee arthroplasty procedures. Contact mechanics for metal-polyethylene articulation in TAA is critical due to the reduced size of the implant and higher expected load, compared with a hip or knee joint. This study was focused on developing a validated computational model to predict contact area in a polyethylene tibial bearing articulating with a metallic talar component in a bicondylar TAA design. Contact area was evaluated at five different flexion angles in an experimental test and in a computational model, per ASTM F2665. The overall contact area values predicted in the computational model matched closely (within 8%) with that measured in the comparator; well within the range reported in the literature. The credibility of the model to sufficiently predict the outputs relative to the experimental data was discussed using the guidelines provided by the recently published ASME V&V 40-2018 standard. Various sensitivities associated with both the model and the comparator, were explored. It was concluded that the validated modeling approach presented in this study demonstrated sufficient accuracy to support the use of modeling for evaluation of contact area of TAA designs. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:1063-1069, 2020., (© 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

Background: Highly crosslinked polyethylene (HXLPE) was developed for its superior wear properties in comparison to conventional polyethylene (CPE). Concern over fatigue resistance has prevented widespread adoption of HXLPE for use in total ankle arthroplasty (TAA). The aim of this study was to determine whether HXLPE has sufficient fatigue strength for total ankle arthroplasty under simulated physiologically relevant motion profiles and loading in the ankle., Methods: Physiologic load and motion profiles representative of walking gait were incorporated into a computational model of a semiconstrained, fixed-bearing TAA to determine the loading state with highest stresses in the HXLPE bearing. Subsequent fatigue testing to 10 million cycles (Mc) at 5600 N was performed to assess bearing strength., Results: Peak stresses in the bearing were predicted at peak axial load and peak dorsiflexion during gait, occurring near heel off. All samples withstood 10 Mc of fatigue loading at that orientation without polyethylene bearing fracture., Conclusion: HXLPE had sufficient fatigue strength to withstand 10 Mc of loading at more than 5 times body weight at the point of peak stresses during simulated gait in total ankle arthroplasty., Clinical Relevance: HXLPE may be mechanically strong enough to withstand the in vivo demands of the ankle. Improvements in wear afforded by HXLPE can be obtained without compromising sufficient polyethylene strength properties in total ankle arthroplasty.

Reverse total shoulder arthroplasty (rTSA) is commonly used in the shoulder replacement surgeries for the relief of pain and to restore function, in patients with grossly deficient rotator cuff. Primary instability due to glenoid loosening is one of the critical complications of rTSA; the implants are designed and implanted such that the motion between the glenoid baseplate and underlying bone is minimized to facilitate adequate primary fixation. Finite element analysis (FEA) is commonly used to simulate the test setup per ASTM F2028-14 for comparing micromotion between designs or configurations to study the pre-clinical indications for stability. The FEA results can be influenced by the underlying modeling assumptions. It is a common practice to simplify the screw shafts by modeling them as cylinders and modeling the screw-bone interface using bonded contact, to evaluate micromotion in rTSA components. The goal of this study was to evaluate the effect of three different assumptions for modeling the screw-bone interface on micromotion predictions. The credibility of these modeling assumptions was examined by comparing the micromotion rank order predicted among three different modular configurations with similar information from the literature. Eight configurations were modeled using different number of screws, glenosphere offset, and baseplate sizes. An axial compression and shear load was applied through the glenosphere and micromotion at the baseplate-bone interface was measured. Three modeling assumptions pertaining to modeling of the screw-bone interface were used and micromotion results were compared to study the effect of number of peripheral screws, eccentricities, and baseplate diameter. The relative comparison of micromotion between configurations using two versus four peripheral screws remained unchanged irrespective of the three modeling assumptions. However, the relative comparison between two inferior offsets and baseplate sizes changed depending on the modeling assumptions used for the screw-bone interface. The finding from this study challenges the generally believed hypothesis that FEA models can be used to make relative comparison of micromotion in rTSA designs as long as the same modeling assumptions are used across all models. The comparisons with previously published work matched the finding from this study in some cases, whereas the comparison was contradicting in other cases. It is essential to validate the computer modeling approach with an experiment using similar designs and methods to increase the confidence in the predictions to make design decisions.

Detailed knowledge of the loading conditions within the human body is essential for the development and optimization of treatments for disorders and injuries of the musculoskeletal system. While loads in the major joints of the lower limb have been the subject of extensive study, relatively little is known about the forces applied to the individual bones of the foot. The objective of this study was to use a detailed musculoskeletal model to compute the loads applied to the metatarsal bones during gait across several healthy subjects. Motion-captured gait trials and computed tomography (CT) foot scans from four healthy subjects were used as the inputs to inverse dynamic simulations that allowed the computation of loads at the metatarsal joints. Low loads in the metatarsophalangeal (MTP) joint were predicted before terminal stance, however, increased to an average peak of 1.9 times body weight (BW) before toe-off in the first metatarsal. At the first tarsometatarsal (TMT) joint, loads of up to 1.0 times BW were seen during the early part of stance, reflecting tension in the ligaments and muscles. These loads subsequently increased to an average peak of 3.0 times BW. Loads in the first ray were higher compared to rays 2-5. The joints were primarily loaded in the longitudinal direction of the bone.

Periacetabular osteolysis is a potentially difficult surgical challenge, which can often drive the choice of reconstruction methods used in revision hip replacement. For smaller defects, impaction of bone grafts may be sufficient, but larger defects can require filler materials that provide structural support in addition to filling a void. This study utilized finite element analysis (FEA) to examine the state of stress in periprosthetic pelvic bone when subjected to a stair-climbing load and in the presence of two simulated defects, to show the effect of implanting a defect repair implant fabricated from Trabecular Metal. Even a small medial bone defect showed a local stress elevation of 4x compared with that seen with an acetabular implant supported by intact periacetabular bone. Local bone stress was much greater (8x the baseline level) for a defect case in which the loss of bone superior to the acetabular implant permitted significant migration. FEA results showed that a repair of the small defect with a Trabecular Metal restrictor lowered periprosthetic bone stress to a level comparable to that in the case of a primary implant. For the larger defect case, the use of a Trabecular Metal augment provides structural stabilization and helps to restore the THR head center. However, stress in the adjacent periprosthetic bone is lower than that observed in the defect-free acetabulum. In the augment case, the load path between the femoral head and the pelvis now passes through the augment as the superior rim of the acetabulum has been replaced. Contact-induced stress in the augment is similar in magnitude to that seen in the superior rim of the baseline case, although the stress pattern in the augment is noticeably different from that in intact bone.