Three-Dimensional Printing of Photoresponsive Biomaterials for Control of Bacterial Microenvironments

Advances in microscopic three-dimensional (μ3D) printing provide a means to microfabricate an almost limitless range of arbitrary geometries, offering new opportunities to rapidly prototype complex architectures for microfluidic and cellular applications. Such 3D lithographic capabilities present a tantalizing prospect for engineering micromechanical components, for example, pumps and valves, for cellular environments composed of smart materials whose size, shape, permeability, stiffness, and other attributes might be modified in real time to precisely manipulate ultralow-volume samples. Unfortunately, most materials produced using μ3D printing are synthetic polymers that are inert to biologically tolerated chemical and light-based triggers and provide low compatibility as materials for cell culture and encapsulation applications. We previously demonstrated feasibility for μ3D printing environmentally sensitive, microstructured protein hydrogels that undergo volume changes in response to pH, ionic strength, and thermal triggers, cues that may be incompatible with sensitive chemical and biological systems. Here, we report the systematic investigation of photoillumination as a minimally invasive and remotely applied means to trigger morphological change in protein-based μ3D-printed smart materials. Detailed knowledge of material responsiveness is exploited to develop individually addressable "smart" valves that can be used to capture, "farm", and then dilute motile bacteria at specified times in multichamber picoliter edifices, capabilities that offer new opportunities for studying cell-cell interactions in ultralow-volume environments.