Angiogenesis, or the formation of new blood vessels from the preexisting vasculature, is a key component in numerous physiologic and pathologic responses and has broad impact in many medical and surgical specialties. In this review, we discuss the key cellular steps which lead to the neovascularization of tissues, and highlight the main molecular mechanisms and mediators in this process. We include discussions on proteolytic enzymes, cell/matrix interactions, pertinent cell signaling pathways, and end with a survey of the mechanisms which lead to the stabilization and maturation of neovasculatures.

The delivery of growth factors to cellularize biocompatible scaffolds like fibrin is a commonly used strategy in tissue engineering. We characterized SMC proliferation and chemotaxis in response to PDGF-BB and FGF-2, alone and in combination, in 2-D culture and in 3-D fibrin hydrogels. While both growth factors induced an equipotent mitogenic response in 2-D culture, only FGF-2 was significantly mitogenic for SMCs in 3-D culture. Only PDGF-BB was significantly chemotactic in a modified Boyden chamber assay. In a 3-D assay of matrix invasion, both growth factors induced an invasive response into the fibrin hydrogel in both proliferating and non-proliferating, mitomycin C (MMC) treated cells. The invasive response was less attenuated by the inhibition of proliferation in PDGF-BB stimulated cells compared with FGF-2 stimulated cells. We conclude that SMCs cultured in fibrin hydrogels have a more robust chemotactic response to PDGF-BB compared with FGF-2, and that the response to FGF-2 is more dependent on cell proliferation. Delivery of both growth factors together potentiates the chemotactic, but not mitogenic response to either growth factor alone.

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