Latorre, M. | bioRxiv Science

bioRxiv2020

Fast, Rate-Independent, Finite Element Implementation of a 3D Constrained Mixture Model of Soft Tissue Growth and Remodeling

Constrained mixture models of soft tissue growth and remodeling can simulate many evolving conditions in health as well as in disease and its treatment, but they can be computationally expensive. In this paper, we derive a new fast, robust finite element implementation based on a concept of mechanobiological equilibrium that yields fully resolved solutions and allows computation of quasi-equilibrated evolutions when imposed perturbations are slow relative to the adaptive process. We demonstrate quadratic convergence and verify the model via comparisons with semi-analytical solutions for arterial mechanics. We further examine the enlargement of aortic aneurysms for which we identify new mechanobiological insights into factors that affect the nearby non-aneurysmal segment as it responds to the changing mechanics within the diseased segment. Because this new 3D approach can be implemented within many existing finite element solvers, constrained mixture models of growth and remodeling can now be used more widely.

bioengineering↗

bioRxiv2019

Paradoxical Aortic Stiffening and Subsequent Cardiac Dysfunction in Hutchinson-Gilford Progeria Syndrome

Hutchinson-Gilford Progeria Syndrome (HGPS) is an ultra-rare disorder with devastating sequelae resulting in early death, presently believed to stem primarily from heart failure secondary to central arterial stiffening. We analyze novel longitudinal cardiovascular data from a mouse model of HGPS (LmnaG609G/G609G) using allometric scaling and advanced computational modelling and show that a late-stage increase in pulse wave velocity, with associated diastolic dysfunction but preserved systolic function, emerges with a loss of aortic function, independent of sex. Specifically, there is a dramatic late-stage loss of smooth muscle function and cells and an excessive accumulation of proteoglycans along the entire aorta, which result in a loss of biomechanical function (contractility and elastic energy storage) and marked structural stiffening despite a distinctly low intrinsic material stiffness that is consistent with the lack of functional lamin A. Importantly, vascular function appears to be normal within the low stress environment of development, only to succumb progressively to pressure-related effects of the lamin A mutation and become extreme in the peri-morbid period. Because the dramatic life-threatening aortic phenotype manifests during the last quarter of life there may be a therapeutic window in maturity that could alleviate concerns with therapies administered during early periods of arterial development.\n\nDisclosuresD.T.B is an equity holder in, and receives research and consulting support from, Inozyme Pharma, Inc. for therapeutics for ENPP1 deficiency. None of the other authors declare any conflict, financial or otherwise.

bioengineering↗