Constitutive relations are fundamental to the solution of problems in continuum mechanics, and are required in the study of, for example, mechanically dominated clinical interventions involving soft biological tissues. Structural continuum constitutive models of arterial layers integrate information about the tissue morphology and therefore allow investigation of the interrelation between structure and function in response to mechanical loading. Collagen fibres are key ingredients in the structure of arteries. In the media (the middle layer of the artery wall) they are arranged in two helically distributed families with a small pitch and very little dispersion in their orientation (i.e. they are aligned quite close to the circumferential direction). By contrast, in the adventitial and intimal layers, the orientation of the collagen fibres is dispersed, as shown by polarized light microscopy of stained arterial tissue. As a result, continuum models that do not account for the dispersion are not able to capture accurately the stress–strain response of these layers. The purpose of this paper, therefore, is to develop a structural continuum framework that is able to represent the dispersion of the collagen fibre orientation. This then allows the development of a new hyperelastic free-energy function that is particularly suited for representing the anisotropic elastic properties of adventitial and intimal layers of arterial walls, and is a generalization of the fibre-reinforced structural model introduced by Holzapfel & Gasser (Holzapfel & Gasser 2001 Comput. Meth. Appl. Mech. Eng. 190, 4379–4403) and Holzapfel et al. (Holzapfel et al. 2000 J. Elast. 61, 1–48). The model incorporates an additional scalar structure parameter that characterizes the dispersed collagen orientation. An efficient finite element implementation of the model is then presented and numerical examples show that the dispersion of the orientation of collagen fibres in the adventitia of human iliac arteries has a significant effect on their mechanical response.

https://royalsocietypublishing.org/doi/pdf/10.1098/rsif.2005.0073

Hyperelastic modelling of arterial layers with distributed collagen fibre orientations

Mechanical models for living cells--a review

Morphological instabilities and surface wrinkling of soft materials such as gels and biological tissues are of growing interest to a number of academic disciplines including soft lithography, metrology, flexible electronics, and biomedical engineering. In this paper, we review some of the recent progresses in experimental and theoretical investigations of instabilities that lead to the emergence and evolution of surface wrinkling, folding and creasing under various geometrical constraints (e.g., thin films, sheets, fibers, particles, tubes, cavities, vesicles and capsules) and loading stimuli (e.g., mechanical forces, growth, atrophy, swelling, shrinkage, van der Waals interactions). Some representative theoretical and numerical approaches aimed at modelling the onset of instabilities as well as the postbuckling evolution involving multiple bifurcations and symmetry-breakings are discussed along with the main characteristics and some possible applications of this rich phenomenon.

Mechanics of morphological instabilities and surface wrinkling in soft materials: a review

Despite major scientific, medical and technological advances over the last few decades, a cure for cancer remains elusive. The disease initiation is complex, and including initiation and avascular growth, onset of hypoxia and acidosis due to accumulation of cells beyond normal physiological conditions, inducement of angiogenesis from the surrounding vasculature, tumour vascularization and further growth, and invasion of surrounding tissue and metastasis. Although the focus historically has been to study these events through experimental and clinical observations, mathematical modelling and simulation that enable analysis at multiple time and spatial scales have also complemented these efforts. Here, we provide an overview of this multiscale modelling focusing on the growth phase of tumours and bypassing the initial stage of tumourigenesis. While we briefly review discrete modelling, our focus is on the continuum approach. We limit the scope further by considering models of tumour progression that do not distinguish tumour cells by their age. We also do not consider immune system interactions nor do we describe models of therapy. We do discuss hybrid-modelling frameworks, where the tumour tissue is modelled using both discrete (cell-scale) and continuum (tumour-scale) elements, thus connecting the micrometre to the centimetre tumour scale. We review recent examples that incorporate experimental data into model parameters. We show that recent mathematical modelling predicts that transport limitations of cell nutrients, oxygen and growth factors may result in cell death that leads to morphological instability, providing a mechanism for invasion via tumour fingering and fragmentation. These conditions induce selection pressure for cell survivability, and may lead to additional genetic mutations. Mathematical modelling further shows that parameters that control the tumour mass shape also control its ability to invade. Thus, tumour morphology may serve as a predictor of invasiveness and treatment prognosis.

https://iopscience.iop.org/article/10.1088/0951-7715/23/1/R01/pdf

Nonlinear modelling of cancer: Bridging the gap between cells and tumours

https://www.math.uci.edu/~lowengrb/RESEARCH/publications/JTBTumor.pdf

Three-dimensional multispecies nonlinear tumor growth--I Model and numerical method.

Since its coming of age in the mid 1960s, continuum biomechanics has contributed much to our understanding of human health as well as to disease, injury, and their treatment. Nevertheless, biomechanics has yet to reach its full potential as a consistent contributor to the improvement of health–care delivery. Because of the inherent complexities of the microstructure and biomechanical behaviour of biological cells and tissues, there is a need for new theoretical frameworks to guide the design and interpretation of new classes of experiments. Because of continued advances in experimental technology, and the associated rapid increase in information on molecular and cellular contributions to behaviour at tissue and organ levels, there is a pressing need for mathematical models to synthesize and predict observations across multiple length– and time–scales. And because of the complex geometries and loading conditions, there is a need for new computational approaches to solve the boundaryand initial–value problems of clinical, industrial, and academic importance. Clearly, much remains to be done. The purpose of this paper is twofold: to review a few of the many achievements in the biomechanics of soft tissues and the tools that allowed them, but, more importantly, to identify some of the open problems that merit increased attention from those in applied mechanics, biomechanics, mathematics and mechanobiology.

J.D. Humphrey

Papers

Review Paper: Continuum biomechanics of soft biological tissues

Age-related Changes in Structure, Function, and Transcriptomics of the Human Proximal Pulmonary Artery