A Practical Method for Patterning Lumens through ECM Hydrogels via Viscous Finger Patterning

Extracellular matrix (ECM) hydrogels with patterned lumens have been used as a framework to generate more physiologically relevant models of tissues, such as vessels and mammary ducts, for biological investigations. However, these models have not found widespread use in research labs or in high-throughput screening applications in large part because the basic methods for generating the lumen structures are generally cumbersome and slow. Here we present viscous finger patterning, a technique to generate lumens through ECM hydrogels in microchannels that can be accomplished using manual or automated pipetting. Passive pumping is used to flow culture media through an unpolymerized hydrogel, creating a lumen through the hydrogel that is subsequently polymerized. Viscous finger patterning takes advantage of viscous fingering, the fluid dynamics phenomenon where a less viscous fluid will flow through and displace a more viscous fluid. We have characterized the technique and used it to create a variety of channel geometries and ECM hydrogel compositions, as well as for the generation of lumens surrounded by multiple hydrogel layers. Because viscous finger patterning can be performed with automated liquid handling systems, high-throughput generation of ECM hydrogels with patterned lumen is enabled. The ability to rapidly and cost-effectively create large numbers of lumens in natural polymers overcomes a critical barrier to the use of more physiologically relevant tissue models in a variety of biological studies and drug screening applications.