| dc.description.abstract | Capillary plexus cultivation is crucial in tissue engineering and regenerative medicine. Vascular endothelial growth factor (VEGF) is one of the primary signal proteins stimulating blood vessel formation, which can be soluble in the medium or protein-bound to the substrate. However, less attention has been paid to distinguishing the specific stimulations by soluble and bound form. On the other hand, theoretical simulations have also been conducted to supplement the expensive experimental works, whereas the mechanisms connecting mechanical and chemical stimuli remained undefined. In this paper, a series of experiments were conducted to explore the respective effects of the two VEGF forms. An in-house synthesized biogel comprising a definite concentration of collagen and fibronectin was designed to cultivate human umbilical vein endothelial cells to form capillary-like networks. The results indicated that the soluble VEGF promptly induced the cells to morphologize from round to elongated shape, which contributed to forming network cords. Simultaneously, the bound VEGF provided long-term stimulation, causing the cells to migrate and differentiate into the final capillary-like network. Furthermore, a hybrid model was developed for simulating short-term in vitro capillary incubation, where the cellular Potts model was used to predict individual cell migration, and continuum mechanics to quantify biogel deformation and VEGF transport dynamics. By bridging the mechanical regulation and chemical stimulation in the model, the results showed good agreement between the predicted network topology and experiments. These results revealed that the capillary-like networks could develop in high integrity only when the mechanical and chemical couplings worked adequately, with the cell morphology and haptotaxis driven by the two forms of VEGF functioning simultaneously. | en_US |