Image-Based Modeling for Improved Functionality in Tissue Engineered Constructs

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DESCRIPTION (provided by applicant): Tissue engineering has tremendous potential to improve health and quality of life, but to produce a mechanically functional tissue requires precise understanding of the interplay between a tissue's microstructure and its overall mechanical properties. Because of the complexity of native tissues, we must begin with a simple test system - a collagen gel - that shares some properties of native tissue and provides a "backbone" for the step-wise addition of other matrix components. In addition, we require an experimental system that simultaneously provides mechanical testing and imaging capabilities, and can track the evolution of local gel network arrangement with load. Finally, a theoretical framework, in the form of a multiscale computational model, is needed to connect each scale and relate microscopic structure to macroscopic function. Our essential hypothesis is that the mechanical properties of an engineered tissue are determined by the microstructure, which can be elucidated with modern imaging techniques. In order to test the hypothesis, we need to assess agreement between experiments and computational models at both the tissue and the network scale. A successful model must do three things: the predicted macroscopic mechanical response must match the gel's; the predicted local matrix rearrangements and strains must match the gel's; and the local matrix representation in the model must reflect the arrangement and composition of components in the gel. We propose first to produce, to image, and to test mechanically collagen gels that differ in fiber alignment. We will simultaneously acquire collagen gel mechanical data via biaxial testing, local alignment via polarized light microscopy, and strain maps via phase correlation. High resolution SEM images will provide supplemental microstructural information. Second, we will generate a multi-scale model based of the gel's local fiber microstructure and compare it to experimental data. The experiment's boundary conditions, loading protocol, and initial alignment map will serve as inputs for the multi-scale model. Comparisons between macroscopic mechanical behavior and local evolution of network orientation, alignment, and strain will be made. Finally, we will repeat this process for gels under confined compression and with the step-wise addition of other matrix components, starting with decorin, a proteoglycan known to effect cell behavior and gel mechanical properties. If successful, this project will lay the groundwork for more rational design of engineered tissues and for future analysis of structure-function relationships in native tissues. A means of repairing or replacing diseased and damaged tissues would be of enormous value to the health and quality of life of a patient