NDLI: In Silico Investigation of Angiogenesis with Growth and Stress Generation Coupled to Local Extracellular Matrix Density

Content Provider	Springer Nature Link
Author	Edgar, Lowell T. Hoying, James B. Weiss, Jeffrey A.
Copyright Year	2015
Abstract	Mechanical interactions during angiogenesis, i.e., traction applied by neovessels to the extracellular matrix and the corresponding deformation, are important regulators of growth and neovascularization. We have previously designed, implemented, and validated a coupled model of angiogenesis in which a discrete microvessel growth model interacts with a continuous finite element mesh through the application of local remodeling sprout stresses (Edgar et al. in Biomech Model Mechanobiol, 2014). However, the initial implementation of this framework does not take matrix density into account when determined these remodeling stresses and is therefore insufficient for the study of angiogenesis within heterogeneous matrix environments such as those found in vivo. The objective of this study was to implement sensitivity to matrix density in the active stress generation within AngioFE in order to allow the study of angiogenic growth within a heterogeneous density environment. We accomplished this by scaling active sprout stresses relative to local matrix density using a scaling factor previously determined from experimental data. We then exercised the new functionality of the model by simulating angiogenesis within four different scenarios: homogeneous density, a narrow gap model, and matrix density gradient, and a construct subjected to repeated loading/unloading and preconditioning. These numerical experiments predicted heterogeneous matrix density in the initially homogeneous case, the closure and alignment of microvessels along a low-density gap, the formation of a unique cap-like structure during angiogenesis within a density gradient, and the alignment of microvessels in the absence of applied load due to preconditioning. The result of these in silico investigations demonstrate how matrix heterogeneity affects neovascularization and matrix deformation and provides a platform for studying angiogenesis in complicated and multi-faceted mechanical environments that microvessels experience in vivo.
Starting Page	1531
Ending Page	1542
Page Count	12
File Format	PDF
ISSN	00906964
Journal	Annals of Biomedical Engineering
Volume Number	43
Issue Number	7
e-ISSN	15739686
Language	English
Publisher	Springer US
Publisher Date	2015-05-21
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Angiogenesis Extracellular matrix Cellular mechanics Cell–matrix interactions Finite element modeling Growth modeling Biomedicine general Biomedical Engineering Biophysics and Biological Physics Mechanics Biochemistry
Content Type	Text
Resource Type	Article
Subject	Biomedical Engineering

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