A multiscale mechanobiological modelling framework using agent-based models and finite element analysis: application to vascular tissue engineering

Abstract

Computational models of mechanobiological systems have been widely used to provide insight into these systems and also to predict their behaviour. In this context, vascular tissue engineering benefits from further attention given the challenges involved in developing functional low calibre vascular grafts with long-term patency. In this study, a novel multiscale mechanobiological modelling framework is presented, which takes advantage of lattice-free agent-based models coupled with the finite element method to investigate the dynamics of VSMC growth in vascular tissue engineering scaffolds. The results illustrate the ability of the mechanobiological modelling approach to capture complex multiscale mechanobiological phenomena. Specifically, the framework enabled the study of the influence of scaffold compliance and loading regime in regulating the growth of VSMCs in vascular scaffolds and their role in development of intimal hyperplasia (IH). The model demonstrates that low scaffold compliance compared to host arteries leads to increased luminal ingrowth and IH development. In addition, culture of a tissue-engineered blood vessel under a pulsatile luminal pressure reduced luminal ingrowth and enhanced collagen synthesis within the scaffold compared to non-pulsatile culture. The mechanobiological framework presented provides a robust platform for testing hypotheses in vascular tissue engineering and lends itself to use as an optimisation design tool.

Vascular Stent Design Optimisation Using Numerical Modelling Techniques

“…Therefore, a novel hybrid model to simulate in-stent restenosis, using coupled ABM and FEM, will now be presented by the authors. This novel approach has recently been applied to model vascularisation in tissue engineered blood vessels (Zahedmanesh et al, 2011) and is adapted and applied here to model in-stent restenosis.…”

“…Where, U is the deviatoric strain energy density, i denotes the deviatoric principle stretches and i and α i are the hyperelastic constants, see (Zahedmanesh & Lally 2009, Zahedmanesh et al, 2011 www.intechopen.com…”

“…Following the FE analysis the values of the arterial damage at each element of the FE model were exported to the ABM module where the response of VSMC to damage was modelled similar to the approach previously outlined in Zahedmanesh et al, (2011).…”

“…More importantly, however, numerical modelling also provides a means to model the biological response to an implant using mechanobiological models whereby the mechanical environment may be used to dictate the growth and remodelling of vascular cells (Boyle et al, 2011;Zahedmanesh & Lally, 2011). With the emergence of Drug Eluting Stents (DES) and gene delivery stents, however, comes a need to include not only the growth and remodelling of the vessel wall but also the temporal and spatial distribution of such therapeutic agents and their influence on cell growth.…”

Deciphering Mechanical Regulation of Chondrogenesis in Fibrin–Polyurethane Composite Scaffolds Enriched with Human Mesenchymal Stem Cells: A Dual Computational and Experimental Approach

“…A reversed FE model approach for parameter fitting was used whereby the material parameters related to the solid matrix were updated iteratively until FE predictions matched the outcome of the compression experiments (Tables 1 and 2). The behavior of the solid phase and the fluid phase of the material were coupled using an effective stress concept whereby an additive decomposition of the stress caused by external loading, r, into an effective stress on the matrix of the tissue, s, and an isotropic pore fluid pressure, P, is used as follows 40,41,43 :…”