Direct laser writing for cardiac tissue engineering: a microfluidic heart on a chip with integrated transducers.

We have designed and fabricated a microfluidic-based platform for sensing mechanical forces generated by cardiac microtissues in a highly-controlled microenvironment. Our fabrication approach combines Direct Laser Writing (DLW) lithography with soft lithography. At the center of our platform is a cylindrical volume, divided into two chambers by a cylindrical polydimethylsiloxane (PDMS) shell. Cells are seeded into the inner chamber from a top opening, and the microtissue assembles onto tailor-made attachment sites on the inner walls of the cylindrical shell. The outer chamber is electrically and fluidically isolated from the inner one by the cylindrical shell and is designed for actuation and sensing purposes. Externally applied pressure waves to the outer chamber deform parts of the cylindrical shell and thus allow us to exert time-dependent forces on the microtissue. Oscillatory forces generated by the microtissue similarly deform the cylindrical shell and change the volume of the outer chamber, resulting in measurable electrical conductance changes. We have used this platform to study the response of cardiac microtissues derived from human induced pluripotent stem cells (hiPSC) under prescribed mechanical loading and pacing.