Design and formulation of functional pluripotent stem cell-derived cardiac microtissues.

Access to robust and information-rich human cardiac tissue models would accelerate drug-based strategies for treating heart disease. Despite significant effort, the generation of high-fidelity adult-like human cardiac tissue analogs remains challenging. We used computational modeling of tissue contraction and assembly mechanics in conjunction with microfabricated constraints to guide the design of aligned and functional 3D human pluripotent stem cell (hPSC)-derived cardiac microtissues that we term cardiac microwires (CMWs). Miniaturization of the platform circumvented the need for tissue vascularization and enabled higher-throughput image-based analysis of CMW drug responsiveness. CMW tissue properties could be tuned using electromechanical stimuli and cell composition. Specifically, controlling self-assembly of 3D tissues in aligned collagen, and pacing with point stimulation electrodes, were found to promote cardiac maturation-associated gene expression and in vivo-like electrical signal propagation. Furthermore, screening a range of hPSC-derived cardiac cell ratios identified that 75% NKX2 Homeobox 5 (NKX2-5)+ cardiomyocytes and 25% Cluster of Differentiation 90 OR (CD90)+ nonmyocytes optimized tissue remodeling dynamics and yielded enhanced structural and functional properties. Finally, we demonstrate the utility of the optimized platform in a tachycardic model of arrhythmogenesis, an aspect of cardiac electrophysiology not previously recapitulated in 3D in vitro hPSC-derived cardiac microtissue models. The design criteria identified with our CMW platform should accelerate the development of predictive in vitro assays of human heart tissue function.

Analytical formulation of modal frequency split in the elliptical mode of SCS micromechanical disk resonators

This paper presents an analytical formulation of frequency splitting observed in the elliptical modes of single crystal silicon (SCS) micromechanical disk resonators. Taking the anisotropic elasticity of SCS into account, new formulae for computing modal mass and modal stiffness are first derived for accurate prediction of the modal frequency. The derived results are in good agreement with finite element simulation, showing a factor of 10 improvement in the prediction accuracy as compared to using the formula for the isotropic case. In addition, the analysis successfully explains the effect of anisotropy on the modal frequency splitting of primary elliptical modes, for which the maximum modal displacement is aligned with the directions of maximum (1 1 0) and minimum (1 0 0) elasticity respectively on a (1 0 0) SCS wafer. The measured frequency splitting of other degenerate modes is due to the manufacturing imperfections. © 2014 IOP Publishing Ltd.