We propose to continue our multiscale mechanical analysis of bioengineered tissues. In the current grant, we have used our two-scale model, in which the microscopic scale represents the collagen fiber network, and the macroscopic scale represents the tissue as a whole;the two scales are fully coupled, and we have implemented the model in three dimensions and developed a biphasic formulation. A finite-element-based computational environment has been developed that allows solution of the model equations efficiently on up to 256 processors. In this renewal, we propose three major extensions to increase the power and applicability of our model: (1) Multiple components, allowing simulation of collagen-fibrin co-gels and tissues remodeled by entrapped cells, (2) Cellular contribution to mechanics, critical for describing cellularized engineered tissues, and (3) Failure mechanics, motivated by the need to make tissues that can withstand in vivo loads without failing and the lack of available tools to predict tissue failure based on composition and structure. Taken together, these steps will create a tool for rational engineering design of replacement tissues based on their functional requirements. Tissue engineering, the creation of replacements for damaged or diseased tissues, is an important area, especially for mechanical tissues such as artery, heart valve, and skin. A major impediment to advances in tissue engineering is our inability to design tissues as we design other engineered products. This project relates directly to public health because it would provide tools to help create the next generation of replacement tissues.

Public Health Relevance

We continue to develop models that allow us to predict the mechanical behavior of bioengineered replacement tissues based on their structure and composition. The work will enable design of the next generation of engineered tissues by helping to determine what components, in what arrangement, are needed to achieve tissue properties similar to the native tissue. This project relates directly to public health, particularly to cardiovascular health, because of the need for mechanically functioning replacements for arteries and heart valves.

National Institute of Health (NIH)
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Research Project (R01)
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Modeling and Analysis of Biological Systems Study Section (MABS)
Program Officer
Hunziker, Rosemarie
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University of Minnesota Twin Cities
Biomedical Engineering
Schools of Engineering
United States
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Witzenburg, Colleen M; Dhume, Rohit Y; Shah, Sachin B et al. (2017) Failure of the Porcine Ascending Aorta: Multidirectional Experiments and a Unifying Microstructural Model. J Biomech Eng 139:
Witzenburg, Colleen M; Barocas, Victor H (2016) A nonlinear anisotropic inverse method for computational dissection of inhomogeneous planar tissues. Comput Methods Biomech Biomed Engin 19:1630-46
Witzenburg, Colleen M; Dhume, Rohit Y; Lake, Spencer P et al. (2016) Automatic Segmentation of Mechanically Inhomogeneous Tissues Based on Deformation Gradient Jump. IEEE Trans Med Imaging 35:29-41
Zhang, Yanhang; Barocas, Victor H; Berceli, Scott A et al. (2016) Multi-scale Modeling of the Cardiovascular System: Disease Development, Progression, and Clinical Intervention. Ann Biomed Eng 44:2642-60
Gyoneva, Lazarina; Hovell, Carley B; Pewowaruk, Ryan J et al. (2016) Cell-matrix interaction during strain-dependent remodelling of simulated collagen networks. Interface Focus 6:20150069
Ban, Ehsan; Barocas, Victor H; Shephard, Mark S et al. (2016) Effect of Fiber Crimp on the Elasticity of Random Fiber Networks With and Without Embedding Matrices. J Appl Mech 83:0410081-410087
Lai, Victor K; Nedrelow, David S; Lake, Spencer P et al. (2016) Swelling of Collagen-Hyaluronic Acid Co-Gels: An In Vitro Residual Stress Model. Ann Biomed Eng 44:2984-2993
Ban, Ehsan; Barocas, Victor H; Shephard, Mark S et al. (2016) Softening in Random Networks of Non-Identical Beams. J Mech Phys Solids 87:38-50
Vanderheiden, Sarah M; Hadi, Mohammad F; Barocas, V H (2015) Crack Propagation Versus Fiber Alignment in Collagen Gels: Experiments and Multiscale Simulation. J Biomech Eng 137:121002
Quindlen, Julia C; Lai, Victor K; Barocas, Victor H (2015) Multiscale Mechanical Model of the Pacinian Corpuscle Shows Depth and Anisotropy Contribute to the Receptor's Characteristic Response to Indentation. PLoS Comput Biol 11:e1004370

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