The SimInSitu project has completed its fourth year, accomplishing most defined tasks, WPs, and milestones. For the hierarchical development and VVUQ approach for the in-silico platform (see image 1), complexity levels 1-6 from a total of 7 were developed and have undergone the planned credibility assessments. In its final year (2025), the SimInSitu project will focus on the completion of the last Complexity Level, which is equivalent to WP7 (in-silico ETR Platform). Below is a brief summary of achievements across Complexity Levels and corresponding Work Packages.
WP1 Scaffold Material Characterization (Complexity Level 1): All scaffold materials were fully characterized using a multitude of test modalities. Additionally, the epistemics uncertainty origination from the test methods and process implementation was evaluated via Round Robin test, while the aleatory uncertainty was evaluated by using a statistically adequate number of test samples. Furthermore, crack-growth was assessed experimentally.
WP2 Scaffold Material Modelling (Complexity Level 1): Relying on these experimental characterization data, complex anisotropic, hyperelastic material models were developed, implemented in commercial Finite Element Method (FEM) software, verified and validated. Using specifically developed Bayesian-statistic based calibration process, all needed material parameters and their distribution functions were evaluated. A separate validation, sensitivity analysis, and uncertainty quantification completed this work.
WP3 Device Modelling (Complexity Level 1 – 4): Within the Device-Modelling work package, all three device-models have been successfully developed and undergone the Model Verification, Validation, and Uncertainty Quantification process using various sources of in-vitro test data. For the Sapien-3 model, two FSI methods have been used – the initially anticipated FlowVision Solver and the alternative (backup) SPH solution. The extensive tiered validation approach using in-vitro structural and hemodynamic validation data was implemented while the uncertainty from pervious WPs was propagated in addition to device-modelling related factors.
WP4 Patient Specific Modelling (Complexity Level 1 – 5): Both development branches, the TAVI Patient-Specific Model, and the Right-Ventricle Outflow Track (RVOT) Patient-Specific Model, were fully developed and successfully verified, validated, and underwent extensive uncertainty quantification. Typical challenges of validating patient-specific / clinical models were overcome through harvesting and analysing extensive pre- and post-treatment data, and through combining cohort-based clinical data with in-vivo preclinical data, which is a further extension of the tiered validation approach.
WP5 ETR Modelling & WP6 Animal Trials (Complexity Level 1 – 6): The Endogenous Tissue Restauration (ETR) process has been developed and calibrated using several animal trials, which were not always fully successful. Additionally, historical data from a large collection of animal trial data was provided by Xeltis to support calibration process. The ETR model was implemented into a Sequential Simulation process. Due to the high complexity and numerical effort, surrogate models were needed and successfully developed using Artificial-Neural-Network models. Finally, the model was validated using available data from WP6 and historical data from preclinical data from Xeltis.
WP7 in-silico ETR Platform (Complexity Level 7): The convergence of all lower complexity levels into this final Complexity Level / work-package has not started yet, except for some strategic assessments of possible In-Silico Clinical Trial approaches. This will be the focus for the final year of the SimInSitu Project.
WP9 Dissemination and Exploitation Pathways: Dissemination and Exploitation is picking up momentum with continuous stream of social-media / web-based contributions, a second combined EU workshop (innovaHeart 2024), a collaboration with other related consortia in the EU funded Horizon Results Booster, and additional publications.
