Title: Angiogenic Factors produced by Hypoxic Cells are a leading driver of Anastomoses in Sprouting Angiogenesis---a computational study,
Abstract: Angiogenesis - the growth of new blood vessels from a pre-existing
vasculature - is key in both physiological processes and on several
pathological scenarios such as cancer progression or diabetic retinopathy. For
the new vascular networks to be functional, it is required that the growing
sprouts merge either with an existing functional mature vessel or with another
growing sprout. This process is called anastomosis. We present a systematic 2D
and 3D computational study of vessel growth in a tissue to address the
capability of angiogenic factor gradients to drive anastomosis formation. We
consider that these growth factors are produced only by tissue cells in
hypoxia, i.e. until nearby vessels merge and become capable of carrying blood
and irrigating their vicinity. We demonstrate that this increased production of
angiogenic factors by hypoxic cells is able to promote vessel anastomoses
events in both 2D and 3D. The simulations also verify that the morphology of
these networks has an increased resilience toward variations in the endothelial
cell's proliferation and chemotactic response. The distribution of tissue
cell`s and the concentration of the growth factors they produce are the major
factors in determining the final morphology of the network.