A Platform for Generation of Chamber-Specific Cardiac Tissues and Disease Modeling.

Tissue engineering using cardiomyocytes derived from human pluripotent stem cells holds a promise to revolutionize drug discovery, but only if limitations related to cardiac chamber specification and platform versatility can be overcome. We describe here a scalable tissue-cultivation platform that is cell source agnostic and enables drug testing under electrical pacing. The plastic platform enabled on-line noninvasive recording of passive tension, active force, contractile dynamics, and Ca2+ transients, as well as endpoint assessments of action potentials and conduction velocity. By combining directed cell differentiation with electrical field conditioning, we engineered electrophysiologically distinct atrial and ventricular tissues with chamber-specific drug responses and gene expression. We report, for the first time, engineering of heteropolar cardiac tissues containing distinct atrial and ventricular ends, and we demonstrate their spatially confined responses to serotonin and ranolazine. Uniquely, electrical conditioning for up to 8 months enabled modeling of polygenic left ventricular hypertrophy starting from patient cells.

4D printed origami-inspired accordion, Kresling and Yoshimura tubes.

Applying tessellated origami patterns to the design of mechanical materials can enhance properties such as strength-to-weight ratio and impact absorption ability. Another advantage is the predictability of the deformation mechanics since origami materials typically deform through the folding and unfolding of their creases. This work focuses on creating 4D printed flexible tubular origami based on three different origami patterns: the accordion, the Kresling and the Yoshimura origami patterns, fabricated with a flexible polylactic acid (PLA) filament with heat-activated shape memory effect. The shape memory characteristics of the self-unfolding structures were then harnessed at 60°C, 75°C and 90°C. Due to differences in the folding patterns of each origami design, significant differences in behaviour were observed during shape programming and actuation. Among the three patterns, the accordion proved to be the most effective for actuation as the overall structure can be compressed following the folding crease lines. In comparison, the Kresling pattern exhibited cracking at crease locations during deformation, while the Yoshimura pattern buckled and did not fold as expected at the crease lines. To demonstrate a potential application, an accordion-patterned origami 4D printed tube for use in hand rehabilitation devices was designed and tested as a proof-of-concept prototype incorporating self-unfolding origami.