Multiscale Modeling in Vascular Disease and Tissue Engineering

Abstract

The human body, and hence the vascular system, is by its very nature a dynamic multiscale hierarchial system. This multiscale nature encompasses different length scales, from molecular and cellular levels to the tissue and organ level, as well as different physical phenomena, such as mechanical, biological and chemical processes. In arteries, vascular cells alter their growth, phenotype and extracellular matrix production in response to macro mechanical changes. These cell level events can in turn accumulate and emerge at the tissue level as pathological conditions such as atherosclerosis and intimal hyperplasia. These cardiovascular diseases evolve through adaptation of cells and tissues over days to months also demonstrating the multiscale nature of vascular diseases with respect to time. The challenge in vascular multiscale modelling is to create a framework which can incorporate the key mechanical, biological and chemical characteristics of this complex system at these various space and time scales to successfully capture the long-term behaviour of the system. Such a framework can then be used to gain additional insights with regards to pathological conditions within the vascular system and to improve the design of medical devices used to treat such pathologies. In the following chapter, a review will be presented of some relevant studies reported in literature which have used multiscale modelling approaches to elucidate the growth and remodelling mechanisms underlying vascular diseases, such as atherosclerosis, in-stent restenosis and intimal hyperplasia.

Exploring arterial tissue microstructural organization using non-Gaussian diffusion magnetic resonance schemes

“…Interestingly, SMC and collagen fibers align themselves with each other and in the media of healthy arteries, SMCs are considered to be enveloped by collagen 16 . Given that collagen production from vascular cells is critical for stability, the presence of SMCs is an indication of vessel’s ability to remodel and maintain such stability 17 .…”

Microphysiological Engineering of Self-Assembled and Perfusable Microvascular Beds for the Production of Vascularized Three-Dimensional Human Microtissues

“…11,12 By recapitulating flow-generated physiological mechanical cues not captured in static culture, these model systems have proven instrumental in advancing our fundamental understanding of vascular endothelial cells. 11,12 With the increasing attention to the multiscale nature of physiological and disease processes in the vascular system, 13 there is now a rapidly growing need to expand the scope of research beyond the cellular level to investigate integrated vascular structure and function at the tissue and organ levels. Despite significant advances, however, existing in vitro vascular models are greatly limited in their ability to meet this important need.…”

“…Over the past few decades, the significant need for such capabilities has stimulated considerable research efforts to develop physiologically relevant in vitro models of the vasculature. Many of these early studies focused on incorporating perfusable cell culture chambers to simulate the dynamic flow environment of blood vessels. , By recapitulating flow-generated physiological mechanical cues not captured in static culture, these model systems have proven instrumental in advancing our fundamental understanding of vascular endothelial cells. , With the increasing attention to the multiscale nature of physiological and disease processes in the vascular system, there is now a rapidly growing need to expand the scope of research beyond the cellular level to investigate integrated vascular structure and function at the tissue and organ levels. Despite significant advances, however, existing in vitro vascular models are greatly limited in their ability to meet this important need.…”