Integrating microchannels and flows into 3D printable granular hydrogel matrices

Microfluidic systems incorporating or contained within hydrogels are important in creating microphysiological systems (MPSs). Often naturally-derived hydrogels are used, as their inherent bioactivity supports dynamic cellular behaviors. Hydrogel biomaterials that are partly or fully synthetic are desirable in engineering systems with specific, designed properties, though they typically lack bioactive features of natural materials without additional molecular design. In particular, engineering synthetic biomaterials to support physiologically relevant, dynamic cellular behaviors is an important design goal. Granular hydrogels inherently permit dynamic cellular activity, owning to porosity between particles and dynamic material properties in the absence of interparticle crosslinking. However, using dynamic granular hydrogels in MPSs requires stable channels to perfuse fluid in these dynamic systems. Here, we establish channels within granular hydrogels to enable perfusion through spatially controlled interparticle crosslinking. Selective crosslinking allowed for the formation of stable channels while allowing hydrogel microparticles between two channels to remain uncrosslinked. This allowed spatiotemporal control of signals within an environment established from microparticles without interparticle crosslinking. Fluorescently tagged molecules allowed for the visualization of controlled soluble gradients between two channels within the device. Additionally, embedded 3D printing processes can be used to specify material composition within the system, demonstrating integrated technology for engineering well-defined hydrogel systems. Integrated microfluidic-based control over soluble signals in a system that is compatible with 3D printing processes will establish a basis for building MPSs for broad applications, and the ability to maintain granular systems in culture without interparticle crosslinking will enable design of synthetic hydrogels that access unique dynamic properties within these systems.