Characterization of the chemotactic and mitogenic response of SMCs to PDGF-BB and FGF-2 in fibrin hydrogels.

Abstract

The delivery of growth factors to cellularize biocompatible scaffolds like fibrin is a commonly used strategy in tissue engineering. We characterized smooth muscle cells (SMC) proliferation and chemotaxis in response to PDGF-BB and FGF-2, alone and in combination, in 2D culture and in 3D fibrin hydrogels. While both growth factors induced an equipotent mitogenic response in 2D culture, only FGF-2 was significantly mitogenic for SMCs in 3D culture. Only PDGF-BB was significantly chemotactic in a modified Boyden chamber assay. In a 3D assay of matrix invasion, both growth factors induced an invasive response into the fibrin hydrogel in both proliferating and nonproliferating, 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.