Tissue development depends, in part, on biomechanical loads. Understanding the biophysical mechanisms of development is integral to designing strategies for the prevention and treatment of developmental abnormalities, as well as for constructing replacement tissues in vitro (tissue engineering). Researchers have benefited greatly from the use of specialized computational models to help understand the mechanics of a number of developmental processes, but progress in the field has been hampered by a lack of general computer codes designed to handle such problems. Developing tissues undergo complex changes in shape as they actively grow, contract, and remodel. Coupling between these processes leads to highly nonlinear problems that require cutting-edge numerical tools. The objective of this proposed research is to develop a general finite element code that can be used to model the biomechanics of developing soft tissue structures. The code will be based on fundamental principles of engineering mechanics.
The specific aims are the following: (1) Develop a nonlinear finite element code that includes volumetric growth, active contraction, and remodeling of individual tissue constituents. (2) Extend the code to include development regulated by mechanical feedback, which is implemented mathematically through specified tissue construction rules. (3) Develop an algorithm to automatically update the geometrical description and the finite element mesh for tissues undergoing geometrical transformations due to large deformations. (4) Construct a finite element model for early brain development, including growth regulated by mechanical feedback. (5) Construct a finite element model for functional adaptation of arteries, including cell growth, matrix remodeling, and smooth muscle tone, all regulated by mechanical feedback. (6) Construct a finite element model for cardiac looping morphogenesis, including cell growth and cytoskeletal contraction regulated by mechanical feedback. The end result of this project will be the first general purpose tissue-level computer code for modeling the biomechanics of development. This software will open up new avenues for studying the mechanics of development in the cardiovascular, nervous, and other systems composed of soft tissue.
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