Cristina Curreli

Total Ankle Arthroplasty (TAA) is a well-established surgical treatment for end-stage ankle arthritis, yet functional outcomes often remain inferior to those of the native joint. This may be because restoring the full physiological range of motion would likely require a custom-made surgery, in which both the prosthetic design and component positioning are defined on the basis of a patient-specific kinematic analysis. The aim of this study is to propose a subject-specific kinematic analysis of an ankle joint implanted with the FAR prosthesis and to investigate the compatibility between prosthesis-induced motion and the physiological motion of the healthy joint. A CT-based 3D model and a 4-bar linkage model were used to estimate the physiological path of the instantaneous centre of rotation during passive plantar–dorsiflexion, while the kinematic constraints of the FAR prosthesis were simultaneously analysed. A novel methodology was proposed, based on an analogy between the FAR implant design and a planetary gear mechanism, to reproduce the physiological kinematics of the natural joint with high fidelity. The results, in terms of overall plantar–dorsiflexion range of motion and ligament behaviour, suggested that the analysed TAA design was unable to fully reproduce the physiological kinematics of the healthy joint model for the subject and virtual surgery considered. Comparison with clinical data demonstrated general agreement in terms of range of motion and meniscal bearing displacement. Overall, the proposed methodology provides a framework for systematically analysing subject-specific ankle joint kinematics after implantation and suggests promising directions for future research.

Femoral bone metastases represent a frequent and severe complication in patients with advanced solid tumours. Although fracture risk assessment commonly relies on Mirels' score, its limited specificity often leads to unnecessary surgical interventions. Patient-specific finite element (FE) models have shown improved accuracy; however, current approaches vary widely in methodology and rarely capture the full fracture process. This study investigates for the first time the application of a linear FE approach based on an incremental element deletion technique to simulate both fracture initiation and propagation in femurs with lytic metastases. Twenty-four patients with femoral lytic lesions were retrospectively analyzed, and model outcomes were compared with clinical results. The proposed approach was evaluated for its ability to stratify patients according to pathological fracture risk, in comparison with conventional simulation methods and the clinically accepted Mirels' score. In addition, a new failure threshold parameter derived from the work required to fracture the femur was investigated. The simulations successfully replicated clinically observed fracture paths and demonstrated strong capability in differentiating high- and low-risk patients. The failure criterion based on the last applied load during simulated crack propagation provided the highest diagnostic performance, achieving excellent sensitivity and specificity. The fracture initiation parameter showed comparable performance, while the work-based parameter appeared more affected by variability in femur visibility. The proposed modeling framework offers the advantage of predicting fracture paths, providing clinically valuable insight, and represents a further step toward improved stratification methods for the clinical management of femoral metastases.

Total hip arthroplasty is one of the most common and rapidly growing surgical procedures, with over one million cases performed annually in the United States. Despite high success rates, revision surgeries remain a significant concern due to complications such as aseptic loosening, often resulting from inadequate primary implant stability. This study presents an automated computational framework that integrates three-dimensional preoperative planning and finite element modeling to predict the primary stability of hip implants. Data obtained from the virtual surgery phase are used to generate subject-specific finite element models, which are executed on high-performance computing systems. The simulation evaluates implant stability by analyzing the contact interaction between the bone and the implant. The pipeline is demonstrated using data from the open-source HFValid collection and a commercial implant. Automation substantially reduced the time required to set up simulations, improving the efficiency on high-performance infrastructure. This integrated computational approach bridges the gap between biomechanical modeling and clinical decision-making and can serve as a preclinical tool for identifying personalized implant strategies and for conducting large-scale virtual cohort studies.

Intraoperative femur fractures are a complication of hip arthroplasty, strongly related to the cementless stem design; this kind of fracture is not always recognised during surgery, and revision surgery may be necessary. The present study aimed to simulate intraoperative crack propagation during stem implantation using subject-specific quasi-static finite element models. Eleven subject-specific finite element femur models were built starting from CT data, and the implant pose and size of a non-commercial cementless stem were identified. The model boundary conditions were set with a compressive load from 1000 N to 10 000 N, to simulate the surgeon's hammering, and element deactivation was used to model the crack propagation. Two damage quantifiers were analysed to identify a threshold value that would allow us to assess if a fracture occurred. A methodology to assess the primary stability of the stem during insertion was also proposed, based on a push-out test. Crack propagation up to the surface was obtained in six patients; in two cases there was no crack generation, while in three patients the crack did not reach the external surface. This study demonstrates the possibility to simulate the propagation of the fracture intraoperatively during hip replacement surgery and generate quantitative information about the bone damage using a virtual cohort of simulated patients with anatomical and physiological variability.

Aseptic loosening is the most common failure mode for total hip arthroplasty, and the design of the implant plays a significant role in influencing the longevity and stability of the implant. Finite Element (FE) models have been demonstrated to be powerful numerical tools that allow for generating information supporting the device’s safety and/or efficacy during pre-clinical assessment. Different authors have proposed FE studies aiming to simulate the long-term stability of the femoral stem; however, multiple improvements are still necessary for translating computational methodologies into clinical practice. This paper provides a comprehensive overview of the modelling procedures for predicting aseptic loosening risk, focusing on cementless femoral stems. The main modelling assumptions, including bone and implant geometry, materials, boundary conditions, and bone–implant interface contact, were summarised and presented. The limitations of various modelling assumptions and their impact on the simulation results were also discussed. The analysis suggests that more rigorous clinical validation for osseointegration models and failure criteria used to determine loosening of the implant should be clearly defined, and efforts should be made to identify the appropriate limit of tolerable conditions.

The need for a framework to justify that a model has sufficient credibility to be used as a basis for internal or external (typically regulatory) decision-making is a primary concern when using modelling and simulation (M&S) in healthcare. This chapter reviews published standards on verification, validation, and uncertainty quantification (VVUQ) as well as regulatory guidance that can be used to establish model credibility in this context, providing a potential starting point for a globally harmonised model credibility framework.

Tuberculosis is one of the leading causes of death in several developing countries and a public health emergency of international concern. In Silico Trials can be used to support innovation in the context of drug development reducing the duration and the cost of the clinical experimentations, a particularly desirable goal for diseases such as tuberculosis. The agent-based Universal Immune System Simulator was used to develop an In Silico Trials environment that can predict the dose–response of new therapeutic vaccines against pulmonary tuberculosis, supporting the optimal design of clinical trials. But before such in silico methodology can be used in the evaluation of new treatments, it is mandatory to assess the credibility of this predictive model. This study presents a risk-informed credibility assessment plan inspired by the ASME V&V 40‐2018 technical standard. Based on the selected context of use and regulatory impact of the technology, a detailed risk analysis is described together with the definition of all the verification and validation activities and related acceptability criteria. The work provides an example of the first steps required for the regulatory evaluation of an agent-based model used in the context of drug development.

In Silico Trials methodologies will play a growing and fundamental role in the development and de-risking of new medical devices in the future. While the regulatory pathway for Digital Patient and Personal Health Forecasting solutions is clear, it is more complex for In Silico Trials solutions, and therefore deserves a deeper analysis. In this position paper, we investigate the current state of the art towards the regulatory system for in silico trials applied to medical devices while exploring the European regulatory system toward this topic. We suggest that the European regulatory system should start a process of innovation: in principle to limit distorted quality by different internal processes within notified bodies, hence avoiding that the more innovative and competitive companies focus their attention on the needs of other large markets, like the USA, where the use of such radical innovations is already rapidly developing.