To make functional tissue engineered blood vessels (TEBVs), it is important to understand the underlying principles that govern structural-functional integrity. The ability to mimic and control the mechanical and biochemical behavior is critical for the success of engineering functional TEBVs. The overall goal of this proposal is to understand the mechanical and biochemical behavior of the TEBVs using combined modeling and experimental approaches at both the cellular and tissue level, relate this behavior to the microstructural components the extracellular matrix and vascular smooth muscle cells, and apply these principles to modify and control the functionality of TEBVs for specific clinical applications. This project brings together an interdisciplinary team of researchers at Boston University with combined expertise in advanced finite element modeling, nonlinear solid mechanics, biomaterials engineering for creating tissue-like constructs, nanofabrication and in situ biophysical cellular assays. This integrative approach will enable an in-depth understanding of the macroscopic mechanical and biochemical behavior of TEBVs and the relationship to their microstructural components. The successful completion of this project will bridge the gap between basic research and clinical applications. The research findings from this project will greatly benefit the researchers in biomechanics, bioengineering and clinical communities. Educationally, the PIs plan to incorporate several educational initiatives into the proposed research program. The PIs complementary research background and techniques will greatly benefit the undergraduate/ graduate students trained through this project.