Most connective tissues are composed primarily of collagen and exhibit hierarchical organization from the nanometer to the millimeter scale. Although the structure and mechanics of collagenous connective tissues have been studied for decades, a clear understanding of the relationships between hierarchical organization and material behavior is severely lacking. This can be attributed in large part to an inability to integrate and couple mechanics between the nanoscale, microscale and mesoscale. In theory, this integration can be accomplished using computational homogenization. The overall aim of this research is to enable multiscale mechanical modeling of hierarchical connective tissues, by developing a software framework and systematically investigating the influence of physical characteristics and assumptions on the predictions from the algorithms. As part of the research, we will develop finite element (FE) based algorithmic and software framework for analysis of nonlinear, multiscale models in biomechanics, based on the open-source FEBio software. To validate these approaches to multiscale modeling, we will construct idealized, multiscale physical surrogates with well-defined nano- and microstructure and perform simultaneous material characterization at the macro- and microscale. This information will be used to develop and validate parametric, multiscale FE models of the physical surrogates. The proposed research will create a significant impact by providing verified, publicly available computational tools, model development and validation methodologies for multiscale mechanics of hierarchical tissues. We anticipate that the results of this research and the software framework will be utilized across a broad range of applications in biology, medicine and beyond. Many heritable diseases directly affect collagen structure and fibrillogenesis, causing relatively well-characterized alterations in structure/organization of type I collagen at multiple levels. The proposed research is fundamentally necessary to enable multiscale mechanical modeling of connective tissues from the nanoscale to the mesoscale.

Public Health Relevance

The proposed research is fundamentally necessary to enable multiscale mechanical modeling of connective tissues from the nanoscale to the mesoscale. An improved understanding of the hierarchical structure and mechanical function of collagen in connective tissues will provide insight into the many disease and injury states that affect collagen structure.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
5R01EB015133-02
Application #
8554764
Study Section
Modeling and Analysis of Biological Systems Study Section (MABS)
Program Officer
Peng, Grace
Project Start
2012-09-30
Project End
2016-08-31
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
2
Fiscal Year
2013
Total Cost
$253,761
Indirect Cost
$84,021
Name
University of Utah
Department
Type
Organized Research Units
DUNS #
009095365
City
Salt Lake City
State
UT
Country
United States
Zip Code
84112
Zitnay, Jared L; Reese, Shawn P; Tran, Garvin et al. (2018) Fabrication of dense anisotropic collagen scaffolds using biaxial compression. Acta Biomater 65:76-87
Erdemir, Ahmet; Hunter, Peter J; Holzapfel, Gerhard A et al. (2018) Perspectives on Sharing Models and Related Resources in Computational Biomechanics Research. J Biomech Eng 140:
Maas, Steve A; LaBelle, Steven A; Ateshian, Gerard A et al. (2018) A Plugin Framework for Extending the Simulation Capabilities of FEBio. Biophys J 115:1630-1637
Maas, Steve A; Ateshian, Gerard A; Weiss, Jeffrey A (2017) FEBio: History and Advances. Annu Rev Biomed Eng 19:279-299
Zitnay, Jared L; Li, Yang; Qin, Zhao et al. (2017) Molecular level detection and localization of mechanical damage in collagen enabled by collagen hybridizing peptides. Nat Commun 8:14913
Maas, Steve A; Erdemir, Ahmet; Halloran, Jason P et al. (2016) A general framework for application of prestrain to computational models of biological materials. J Mech Behav Biomed Mater 61:499-510
Reese, Shawn P; Farhang, Niloofar; Poulson, Randy et al. (2016) Nanoscale Imaging of Collagen Gels with Focused Ion Beam Milling and Scanning Electron Microscopy. Biophys J 111:1797-1804
Sibole, Scott C; Maas, Steve; Halloran, Jason P et al. (2016) Evaluation of a post-processing approach for multiscale analysis of biphasic mechanics of chondrocytes, DOI: 10.1080/10255842.2013.809711. Comput Methods Biomech Biomed Engin 19:ii
Edgar, Lowell T; Hoying, James B; Weiss, Jeffrey A (2015) In Silico Investigation of Angiogenesis with Growth and Stress Generation Coupled to Local Extracellular Matrix Density. Ann Biomed Eng 43:1531-42
Edgar, Lowell T; Maas, Steve A; Guilkey, James E et al. (2015) A coupled model of neovessel growth and matrix mechanics describes and predicts angiogenesis in vitro. Biomech Model Mechanobiol 14:767-82

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