We propose to continue our multiscale mechanical analysis of bioengineered tissues. In the previous grant period, we used a two-scale model, with the microscopic scale representing collagen fibers via a discrete network and the macroscopic scale representing tissue as a whole via continuous finite elements;the two scales are fully coupled, and we have applied the model to a variety of systems. Major advances include (1) An image-based model generation scheme, (2) Biphasic analysis, including both network-fluid and network-solid systems, (3) Dynamic modification of individual fibers to represent enzymatic degradation or damage, and (4) Experimental studies of pure gels (collagen) and co-gels (collagen-agarose and collagen-fibrin). The current model has been extremely successful, but there is still more work to be done before a proper materials science of engineered tissues can be said to exist. In this renewal, we propose three major advances that will create the next generation theoretical description of a bioengineered tissue: (1) We will add cell mechanics to the model via a third scale. The three scales will represent the tissue, the cell-matrix composite with discrete cells, and the fiber matrix. This model will be a significant advance over existing models of cell-gel composites in that it will provide a mechanism to capture the internal mechanics of the matrix and to explore a wide range of cytomechanical models. (2) We will extend our initial model of fiber failure into a model that can capture progressive damage to the fibers and damage to the interfibrillar material, the latter potentially important because of the high strength of collagen relative to many other ECM components. (3) We will supplement our existing model with viscoelastic terms due to the fiber network, the interfibrillar material, and he cells, as well as add an extra water phase to the model to account for the effect of interstitial flow through the interfibrillar materials (extending our earlier biphasic models). The first advanc will address tissue complexity but remains prefailure and quasistatic. The second will allow the study of failing or damaged systems, and the third will capture dynamic tissue behavior. All three proposed theoretical advances will be combined with experiments to specify and test the models. 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, especially to the creation and use of wholly bioengineered tissues, is our inability to design tissues as we design other engineered products. This project relates directly to public health because it will provide tools to help creae 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, particulary 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)
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Peng, Grace
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University of Minnesota Twin Cities
Biomedical Engineering
Schools of Engineering
United States
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Shah, Sachin B; Witzenburg, Colleen; Hadi, Mohammad F et al. (2014) Prefailure and failure mechanics of the porcine ascending thoracic aorta: experiments and a multiscale model. J Biomech Eng 136:021028
Nagel, Tina M; Hadi, Mohammad F; Claeson, Amy A et al. (2014) Combining displacement field and grip force information to determine mechanical properties of planar tissue with complicated geometry. J Biomech Eng 136:
Nagel, Tina M; Zitnay, Jared L; Barocas, Victor H et al. (2014) Quantification of continuous in vivo flexion-extension kinematics and intervertebral strains. Eur Spine J 23:754-61
Zhang, L; Lake, S P; Barocas, V H et al. (2013) Cross-Linked Fiber Network Embedded in Elastic Matrix. Soft Matter 9:6398-6405
Zhang, Lijuan; Lake, Spencer P; Lai, Victor K et al. (2013) A coupled fiber-matrix model demonstrates highly inhomogeneous microstructural interactions in soft tissues under tensile load. J Biomech Eng 135:011008
Hadi, Mohammad F; Barocas, Victor H (2013) Microscale fiber network alignment affects macroscale failure behavior in simulated collagen tissue analogs. J Biomech Eng 135:021026
Aghvami, Maziar; Barocas, V H; Sander, E A (2013) Multiscale mechanical simulations of cell compacted collagen gels. J Biomech Eng 135:71004
Lai, Victor K; Hadi, Mohammad F; Tranquillo, Robert T et al. (2013) A multiscale approach to modeling the passive mechanical contribution of cells in tissues. J Biomech Eng 135:71007
Hadi, M F; Sander, E A; Ruberti, J W et al. (2012) Simulated remodeling of loaded collagen networks via strain-dependent enzymatic degradation and constant-rate fiber growth. Mech Mater 44:72-82
Lai, Victor K; Lake, Spencer P; Frey, Christina R et al. (2012) Mechanical behavior of collagen-fibrin co-gels reflects transition from series to parallel interactions with increasing collagen content. J Biomech Eng 134:011004

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