Cardiovascular disease remains the leading cause of mortality in Western world. Current treatments for vascular disease include vascular grafting and stenting. Owing to the limitations of current treatments, over the past few years a significant research effort has been directed towards the development of tissue engineered blood vessels (TEBV). However, a TEBV that matches the biological and biomechanical functionality of natural blood vessels has yet to be developed. One of the strategies employed in the development of TEBVs involves the use of decellularised or synthetic scaffolds, which are seeded with the patient’s own cells and physically conditioned in bioreactors, with a view to developing blood-vessel-equivalent functionality prior to implantation. Along this line, the physical conditioning in bioreactors needs to replicate the in vivo haemodynamic stimulation, in order to guide normal cellular function and appropriate graft remodelling and regeneration. However, the in vitro set up, with the cells seeded on to a decellularised or synthetic scaffold and subjected to pulsatile flow in a bioreactor, does not represent a physiological scenario. Even if the bioreactor is able to simulate physiological haemodynamic conditions at the macroscale, the stimulus that would be transferred to the microscale and sensed by the cells to regulate their function is likely to be different from the micro-stimulus sensed by the cells in vivo in a native blood vessel. Therefore, in order to appropriately guide cellular function in vitro it would be necessary to assess the level of micro-stimulus sensed by the native cells in the native blood vessel in vivo, with a view to simulating this micro-stimulus in artificial bioreactor environments for conditioning the cells that are seeded onto scaffolds with non-native histoarhitectures. However, this micro-stimulus that vascular cells are exposed to in vivo cannot be assessed experimentally. The advances in computing and software resources have enabled the use of computational modelling for conducting such assessments. The aim of this project was to develop computational models for assessing the stress and strain fields on the vascular tissue and cells at the macro- and micro-scales, which will assist the bioreactor conditioning towards the development of tissue engineered vascular grafts. The 3D macro-scale simulations involved fluid-structure interaction (FSI) analysis with main focus on the strain on the vascular wall, while the 2D micro-scale simulation involved finite element analysis (FEA), focused on the local strain variation. All simulations were based on relatively physiological structures after experimental assessment. The simulations were also compared against experimental findings for strain. Macro strain resulted in approximately 11% for FSI against 19% for experimental pressure test. However, the limitations of the experimental procedure overestimated the performed dilation. Moreover, the 2D FEA simulations performed under different material properties, as an attempt to approach more physiological conditions, and under uniaxial strain only. The variation in material properties indicated inhomogeneicity, as expected, and also seemed to replicate the local strain spread when compared to experimental findings. However, further investigation is needed, which will involve the development of 3D FEA models, more physiological material properties and biaxial stretching. Under these circumstances, more information may be extracted and eventually applied to the bioreactor conditioning. Nevertheless, the novel methodology developed in this project for the study of the strain at the micro-level allows the further investigation on the tissue micro-environment.
