A computational multi-scale approach to investigate mechanically-induced changes in tricuspid valve anterior leaflet microstructure

Vineet S. Thomas, Victor Lai, Rouzbeh Amini

Research output: Contribution to journalArticle

Abstract

The tricuspid valve is an atrioventricular valve that prevents blood backflow from the right ventricle into the right atrium during ventricular contractions. It is important to study mechanically induced microstructural alterations in the tricuspid valve leaflets, as this aids both in understanding valvular diseases and in the development of new engineered tissue replacements. The structure and composition of the extracellular matrix (ECM) fiber networks are closely tied to an overall biomechanical function of the tricuspid valve. In this study, we conducted experiments and implemented a multiscale modeling approach to predict ECM microstructural changes to tissue-level mechanical responses in a controlled loading environment. In particular, we characterized a sample of a porcine anterior leaflet at a macroscale using a biaxial mechanical testing method. We then generated a three-dimensional finite element model, to which computational representations of corresponding fiber networks were incorporated based on properties of the microstructural architecture obtained from small angle light scattering. Using five different biaxial boundary conditions, we performed iterative simulations to obtain model parameters with an overall R2 value of 0.93. We observed that mechanical loading could markedly alter the underlying ECM architecture. For example, a relatively isotropic fiber network (with an anisotropy index value α of 28%) became noticeably more anisotropic (with an α of 40%) when it underwent mechanical loading. We also observed that the mechanical strain was distributed in a different manner at the ECM/fiber level as compared to the tissue level. The approach presented in this study has the potential to be implemented in pathophysiologically altered biomechanical and structural conditions and to bring insights into the mechanobiology of the tricuspid valve. Statement of Significance: Quantifying abnormal cellar/ECM-level deformation of tricuspid valve leaflets subjected to a modified loading environment is of great importance, as it is believed to be linked to valvular remodeling responses. For example, developing surgical procedures or engineered tissue replacements that maintain/mimic ECM-level mechanical homeostasis could lead to more durable outcomes. To quantify leaflet deformation, we built a multiscale framework encompassing the contributions of disorganized ECM components and organized fibers, which can predict the behavior of the tricuspid valve leaflets under physiological loading conditions both at the tissue level and at the ECM level. In addition to future in-depth studies of tricuspid valve pathologies, our model can be used to characterize tissues in other valves of the heart.

Original languageEnglish (US)
Pages (from-to)524-535
Number of pages12
JournalActa Biomaterialia
Volume94
DOIs
StatePublished - Aug 1 2019

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Tricuspid Valve
Extracellular Matrix
Microstructure
Tissue
Fibers
Small Angle Scattering
Biophysics
Controlled Environment
Mechanical testing
Heart Valves
Anisotropy
Pathology
Heart Atria
Light scattering
Heart Ventricles
Homeostasis
Blood
Swine
Boundary conditions
Light

Keywords

  • Collagen
  • Extracellular matrix
  • Finite element
  • Mechanobiology
  • Non-affine deformation
  • Representative volume element

PubMed: MeSH publication types

  • Journal Article

Cite this

A computational multi-scale approach to investigate mechanically-induced changes in tricuspid valve anterior leaflet microstructure. / Thomas, Vineet S.; Lai, Victor; Amini, Rouzbeh.

In: Acta Biomaterialia, Vol. 94, 01.08.2019, p. 524-535.

Research output: Contribution to journalArticle

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abstract = "The tricuspid valve is an atrioventricular valve that prevents blood backflow from the right ventricle into the right atrium during ventricular contractions. It is important to study mechanically induced microstructural alterations in the tricuspid valve leaflets, as this aids both in understanding valvular diseases and in the development of new engineered tissue replacements. The structure and composition of the extracellular matrix (ECM) fiber networks are closely tied to an overall biomechanical function of the tricuspid valve. In this study, we conducted experiments and implemented a multiscale modeling approach to predict ECM microstructural changes to tissue-level mechanical responses in a controlled loading environment. In particular, we characterized a sample of a porcine anterior leaflet at a macroscale using a biaxial mechanical testing method. We then generated a three-dimensional finite element model, to which computational representations of corresponding fiber networks were incorporated based on properties of the microstructural architecture obtained from small angle light scattering. Using five different biaxial boundary conditions, we performed iterative simulations to obtain model parameters with an overall R2 value of 0.93. We observed that mechanical loading could markedly alter the underlying ECM architecture. For example, a relatively isotropic fiber network (with an anisotropy index value α of 28{\%}) became noticeably more anisotropic (with an α of 40{\%}) when it underwent mechanical loading. We also observed that the mechanical strain was distributed in a different manner at the ECM/fiber level as compared to the tissue level. The approach presented in this study has the potential to be implemented in pathophysiologically altered biomechanical and structural conditions and to bring insights into the mechanobiology of the tricuspid valve. Statement of Significance: Quantifying abnormal cellar/ECM-level deformation of tricuspid valve leaflets subjected to a modified loading environment is of great importance, as it is believed to be linked to valvular remodeling responses. For example, developing surgical procedures or engineered tissue replacements that maintain/mimic ECM-level mechanical homeostasis could lead to more durable outcomes. To quantify leaflet deformation, we built a multiscale framework encompassing the contributions of disorganized ECM components and organized fibers, which can predict the behavior of the tricuspid valve leaflets under physiological loading conditions both at the tissue level and at the ECM level. In addition to future in-depth studies of tricuspid valve pathologies, our model can be used to characterize tissues in other valves of the heart.",
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