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Abstract: We present a simple bench-top technique to produce centimeter long concentration gradients in biomaterials incorporating soluble, material, and particle gradients. By patterning hydrophilic regions on a substrate, a stripe of prepolymer solution is held in place on a glass slide by a hydrophobic boundary. Adding a droplet to one end of this “pre-wet” stripe causes a rapid capillary flow that spreads the droplet along the stripe to generate a gradient in the relative concentrations of the droplet and pre-wet solutions. The gradient length and shape are controlled by the pre-wet and droplet volumes, stripe thickness, fluid viscosity and surface tension. Gradient biomaterials are produced by crosslinking gradients of prepolymer solutions. Demonstrated examples include a concentration gradient of cells encapsulated in three dimensions (3D) within a homogeneous biopolymer and a constant concentration of cells encapsulated in 3D within a biomaterial gradient exhibiting a gradient in cell spreading. The technique employs coated glass slides that may be purchased or custom made from tape and hydrophobic spray. The approach is accessible to virtually any researcher or student and should dramatically reduce the time required to synthesize a wide range of gradient biomaterials. Moreover, since the technique employs passive mechanisms it is ideal for remote or resource poor settings. [Copyright &y& Elsevier]

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. [Copyright &y& Elsevier]