#	Pagina
attuale pagina	/open-h2020/projects/212941/results.html

Report

Teaser, summary, work performed and final results

Periodic Reporting for period 1 - InSilc (InSilc: In-silico trials for drug-eluting BVS design, development and evaluation)

Teaser

Summary

InSilc project is funded by the European Commission within the Horizon 2020 Research and Innovation program with â‚¬ 5.8 M. Thirteen partners from ten different countries, including universities, medical centres, research centres and enterprises, participate in the project, providing the necessary experience to ensure the success of the project in all its stages of development. The coronary artery disease (CAD) is caused by the build-up of atherosclerotic plaques inside the coronary arteries and remains the leading cause of mortality worldwide and accounts for over 4 million deaths per year, close to half of all deaths in Europe.
The global bioresorbable Coronary stents market size Is estimated currently at 150 million and is anticipated to grow over 183 million till 2024.
The advents of drug-eluting BVS have emerged as a potential major breakthrough for treatment of coronary artery lesions. The aim of InSilc is to develop an in-silico clinical trial (ISCT) platform for designing, developing and assessing drug-eluting bioresorbable vascular scaffolds (BVS). â€œVirtualâ€ patients would be given a â€œvirtualâ€ drug-eluting BVS, for observing the performance of the scaffold, assess and quantify the intended effect, with a deeper understanding than normal trials can provide. InSilc will assist in the development, assessment and optimization of the drug-eluting BVS and deliver accurate and reliable information to the Stent Biomedical Industry.

Work performed

In WP1, administrative and financial management including quality control and ethics and legal considerations is performed.
In WP2, we are defining a clear business plan for the project expected exploitable products. Dissemination and communication of projectâ€™s results, attracting stakeholders and raising of the awareness of InSilc and performance of an economical evaluation of InSilc results are ongoing.
The work carried out in WP3 so far included: (i) in vitro mechanical testing as required by the Standards on coronary stents, (ii) animal studies performed in swine model of hypercholesterolemia, (iii) in vitro models of molecular pathways of intrastent restenosis (ISR) and thrombosis.
In WP4, the following key tasks/work have been accomplished: (i) collection of retrospective data from the participating partners, (ii) design of 3D reconstruction tool of coronary arteries and plaque morphology preliminary conceptual architecture, creation/extension of different methods and algorithms for processing data from different imaging modalities (IVUS, OCT, QCA, CT) to be used for the 3D reconstruction of the arterial wall/plaques, (iii) analysis and relevant results of the coronary ostium pressure variability model and retraining of the statistical model of ostium pressure variability, (iv) development of plaque growth models integrating comorbidities (hypertension, diabetes) and creation of a first approach for a multivariate statistical model to be used for the generation of virtual clinical data.
WP5 is divided in three tasks: (i) Task 5.1 which is devoted to the definition and implementation of the virtual models of various coronary BVS implantation systems, (ii) Task 5.2, where the virtual models developed in Task 5.1 are coupled to virtual set-ups of various testing conditions for implementing the Mechanical Modelling Module, which allow to in silico mimic all the in vitro mechanical tests required by technical Standards, (iii) Task 5.3, where the virtual models developed in Task 5.1 are combined to virtual stenotic coronary arteries for implementing the Deployment Module for accurately in silico simulating the drug-eluting BVS deployment.
In WP6, the development of the following modules is ongoing: (i) the Fluid Dynamics Module, (ii) Myocardial Perfusion Module, (iii) the Drug-Delivery Module and (iv) the Degradation Module, which provide information of the medium/ long-term effects of the drug-eluting BVS implantation.
In WP7, (i) user needs have been analysed and transformed into requirements and a platform architecture, (ii) an initial version of the InSilc cloud platform has been created. Feedback from many partners has been collected and is taken into account during the further development process, (iii) initial data converters have been generated, supporting the data flow between the modules as well as the cloud-based 3D model visualization, (iv) a first version of the 3D web-based viewer to visualize the output of InSilc modules has been integrated with the front-end of the platform.
In WP8, focus was provided on the establishment of the clinical study protocol. The main issue discussed among participating partners was the selection of the stent device to be used, especially under the recent developments in BVS stent industry. The UOI protocol was approved by the local ethical committee, the Erasmus MC protocol is submitted to the local ethical committee. The clinical study conducted at the Erasmus MC is a multicenter trial. UOI runs a single centre trial. Finally, Task 8.3 focused at the formulation of a preliminary framework for the platform adoption.

Final results

InSilc has already produced and will produce a wide range of beyond the SoA results. In particular, on the cellural level, a wide gene expression profile on vascular wall cells will be obtained and integration with Agent-based and Computational models is planned. In the plaque growth model, comorbid conditions (hypertension, diabetes) were included in the plaque growth model, a statistical model was developed which provides virtual clinical data and a first version of virtual population for in silico trials in stenting field was generated. In short term modelling, material properties were specifically characterized for each implantation system and models of BVS implantation systems were validated. We have developed a validated and consistent numerical framework for virtual ISO Standards mechanical tests on BVS implantation systems. A numerical framework to be used for in silico BVS deployment in patient-specific coronary stenotic arteries and a versatile tool able to predict both the short-term behaviour (Deployment Module) of a coronary BVS after implantation (endpoints as in a clinical trial) and to provide inputs for the other modules on the in silico platform to foresee also medium/ long term response (Fluid Dynamics Module, Drug delivery Module, Degradation Module, Myocardial Perfusion module) were developed. In addition, different scenarios linked to the real clinical trials have been identified and association of in silico modules outputs with clinical endpoints have been defined. The validation of the short and long term models will allow the implementation of a robust in-silico stents clinical trial platform which will be coupled with a tailored virtual population and foresees to significantly reduce the required resources during BVS stent design and development. Moreover, InSilc platform will contribute to the liaison of in silico clinical trial approaches and regulatory pathways so as to foster the wider incorporation of in silico trials in clinical practice.