title: Convection-driven generation of long-range material gradients.
abstract: Natural materials exhibit anisotropy with variations in soluble factors, cell distribution, and matrix properties. The ability to recreate the heterogeneity of the natural materials is a major challenge for investigating cell-material interactions and for developing biomimetic materials. Here we present a generic fluidic approach using convection and alternating flow to rapidly generate multi-centimeter gradients of biomolecules, polymers, beads and cells and cross-gradients of two species in a microchannel. Accompanying theoretical estimates and simulations of gradient growth provide design criteria over a range of material properties. A poly(ethylene-glycol) hydrogel gradient, a porous collagen gradient and a composite material with a hyaluronic acid/gelatin cross-gradient were generated with continuous variations in material properties and in their ability to regulate cellular response. This simple yet generic fluidic platform should prove useful for creating anisotropic biomimetic materials and high-throughput platforms for investigating cell-microenvironment interactions.
authors.affiliation: Center for Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA 02139, USA.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Du
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Hancock
authors.forename: Jiankang
authors.initials: J
authors.lastname: He
authors.forename: Jose L
authors.initials: JL
authors.lastname: Villa-Uribe
authors.forename: Ben
authors.initials: B
authors.lastname: Wang
authors.forename: Donald M
authors.initials: DM
authors.lastname: Cropek
authors.forename: Ali
authors.initials: A
authors.lastname: Khademhosseini
mesh_terms: D001672:Biocompatible Materials / Q000737:chemistry*; D018481:Convection; D003911:Dextrans / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives / Q000378:metabolism; D005453:Fluorescence; D006801:Humans; D012235:Rhodamines / Q000378:metabolism
chemical_list: D001672:Biocompatible Materials; D003911:Dextrans; D012235:Rhodamines; C015219:fluorescein isothiocyanate dextran; C051311:rhodamine dextran; D016650:Fluorescein-5-isothiocyanate