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In small animals with a relatively simple structure and organization, direct diffusion is sufficient for the transport of nutrients, gases and waste materials to and from individual cells. However, in the evolution of the higher metazoan animals, some cells become distant from the external environment, creating evolutionary pressure for selection of those with rudimentary circulatory systems [1]. Thus, large multicellular organisms developed complex, cell-lined, vascular systems, allowing transport of water, ions and nutrients to remote parts of the organism, and removal of waste products.Complex organisms developed reliable means to control the development of the circulatory system during embryogenesis (vasculogenesis), as well as mechanisms to compensate for the loss of segments of the circulatory system. This compensation can be achieved through the formation of new collateral vessels without a media layer (angiogenesis), and through the enlargement of smaller, pre-existing, vessels into full arteries possessing a media layer (arteriogenesis). However, these natural processes of collateral development appear to be primarily mechanisms for survival, and are often inadequate for full recovery of normal vascular function. … * Corresponding author. Tel.: +351-39-400-414; fax: +351-39-780-552 lgoncalv{at}ci.uc.pt sxe2{at}mhg.edu j.j.piek{at}amc.uva.nl

Controlling collateral development: the difficult task of mimicking mother nature