Engineering multicellular living systems-a Keystone Symposia report.

The ability to engineer complex multicellular systems has enormous potential to inform our understanding of biological processes and disease and alter the drug development process. Engineering living systems to emulate natural processes or to incorporate new functions relies on a detailed understanding of the biochemical, mechanical, and other cues between cells and between cells and their environment that result in the coordinated action of multicellular systems. On April 3-6, 2022, experts in the field met at the Keystone symposium "Engineering Multicellular Living Systems" to discuss recent advances in understanding how cells cooperate within a multicellular system, as well as recent efforts to engineer systems like organ-on-a-chip models, biological robots, and organoids.

Programming Cellular Alignment in Engineered Cardiac Tissue via Bioprinting Anisotropic Organ Building Blocks.

The ability to replicate the 3D myocardial architecture found in human hearts is a grand challenge. Here, the fabrication of aligned cardiac tissues via bioprinting anisotropic organ building blocks (aOBBs) composed of human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) is reported. A bioink composed of contractile cardiac aOBBs is first generated and aligned cardiac tissue sheets with linear, spiral, and chevron features are printed.

Orthogonally induced differentiation of stem cells for the programmatic patterning of vascularized organoids and bioprinted tissues.

The generation of organoids and tissues with programmable cellular complexity, architecture and function would benefit from the simultaneous differentiation of human induced pluripotent stem cells (hiPSCs) into divergent cell types. Yet differentiation protocols for the overexpression of specific transcription factors typically produce a single cell type. Here we show that patterned organoids and bioprinted tissues with controlled composition and organization can be generated by simultaneously co-differentiating hiPSCs into distinct cell types via the forced overexpression of transcription factors, independently of culture-media composition.

Innervated, Self-Sensing Liquid Crystal Elastomer Actuators with Closed Loop Control.

The programmable assembly of innervated LCE actuators (iLCEs) with prescribed contractile actuation, self-sensing, and closed loop control via core-shell 3D printing is reported. This extrusion-based direct ink writing method enables coaxial filamentary features composed of pure LM core surrounded by an LCE shell, whose director is aligned along the print path. Specifically, the thermal response of the iLCE fiber-type actuators is programmed, measured, and modeled during Joule heating, including quantifying the concomitant changes in fiber length and resistance that arise during simultaneous heating and self-sensing.