Three-Dimensional Chemical Patterns for Cellular Self-Organization†

In nature, three dimensional (3D) chemical patterns are generated and sustained with precisely controlled spatial and temporal profiles, on a variety of length and time scales.[1,2] Several studies have outlined the need for the development of in vitro methodologies that replicate the 3D spatio-temporal chemical patterns associated with chemotaxis, cell signaling, angiogenesis, homeostasis and immune surveillance.[3–7] There are a number of in vitro microfluidic systems that have been developed to mimic in vivo chemical micro-environments such as the creation of interleukin-8 gradients to study neutrophil chemotaxis.[8] However, microfluidic systems are inherently planar (2D) and their overall size and dependency on external equipment to enable active flow restricts their applicability.[9–11] Hence, the development of passive systems that enable diffusion-based 3D chemical pattern formation is attractive since they can be readily utilized to generate and sustain patterns within cell culture, homogeneous gels and other stationary media. Existing microparticles and reservoirs[12] can be utilized to create chemical patterns in 3D environments, however, the pre-dominant spatial release profile is one that is spherically symmetric[13] (Figure 1a).