Investigating the effect of drug release on in-stent restenosis: a hybrid continuum – agent-based modelling approach

Corti, A., McQueen, A., Migliavacca, F., Chiastra, C. and McGinty, S. (2023) Investigating the effect of drug release on in-stent restenosis: a hybrid continuum – agent-based modelling approach. Computer Methods and Programs in Biomedicine, 241, 107739. (doi: 10.1016/j.cmpb.2023.107739)

Abstract

Background and objective: In-stent restenosis (ISR) following percutaneous coronary intervention with drug-eluting stent (DES) implantation remains an unresolved issue, with ISR rates up to 10%. The use of antiproliferative drugs on DESs has significantly reduced ISR. However, a complete knowledge of the mechanobiological processes underlying ISR is still lacking. Multiscale agent-based modelling frameworks, integrating continuum- and agent-based approaches, have recently emerged as promising tools to decipher the mechanobiological events driving ISR at different spatiotemporal scales. However, the integration of sophisticated drug models with an agent-based model (ABM) of ISR has been under-investigated. The aim of the present study was to develop a novel multiscale agent-based modelling framework of ISR following DES implantation. Methods: The framework consisted of two bi-directionally coupled modules, namely (i) a drug transport module, simulating drug transport through a continuum-based approach, and (ii) a tissue remodelling module, simulating cellular dynamics through an ABM. Receptor saturation (RS), defined as the fraction of target receptors saturated with drug, is used to mediate cellular activities in the ABM, since RS is widely regarded as a measure of drug efficacy. Three studies were performed to investigate different scenarios in terms of drug mass (DM), drug release profiles (RP), coupling schemes and idealized vs. patient-specific artery geometries. Results: The studies demonstrated the versatility of the framework and enabled exploration of the sensitivity to different settings, coupling modalities and geometries. As expected, changes in the DM, RP and coupling schemes illustrated a variation in RS over time, in turn affecting the ABM response. For example, combined small DM – fast RP led to similar ISR degrees as high DM – moderate RP (lumen area reduction of ∼13/17% vs. ∼30% without drug). The use of a patient-specific geometry with non-equally distributed struts resulted in a heterogeneous RS map, but did not remarkably impact the ABM response. Conclusion: The application to a patient-specific geometry highlights the potential of the framework to address complex realistic scenarios and lays the foundations for future research, including calibration and validation on patient datasets and the investigation of the effects of different plaque composition on the arterial response to DES.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Mcginty, Dr Sean and Corti, Anna and McQueen, Mr Alistair
• Authors: Corti, A., McQueen, A., Migliavacca, F., Chiastra, C., and McGinty, S.
• College/School: College of Science and Engineering > School of Engineering; College of Science and Engineering > School of Engineering > Biomedical Engineering
• Journal Name: Computer Methods and Programs in Biomedicine
• Publisher: Elsevier
• ISSN: 0169-2607
• ISSN (Online): 1872-7565
• Published Online: 01 August 2023
• Copyright Holders: Copyright © 2023 The Authors
• First Published: First published in Computer Methods and Programs in Biomedicine 241:107739
• Publisher Policy: Reproduced under a Creative Commons license

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
303232		EPSRC Centre for Multiscale soft tissue mechanics with MIT and POLIMI (SofTMech-MP)	Xiaoyu Luo	Engineering and Physical Sciences Research Council (EPSRC)	EP/S030875/1	M&S - Mathematics