M. Wiendels
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7 records found
1
We present partially-transparent ionic polymer–metal composite (IPMC) actuators and their seamless integration into microphysiological systems, to enable dynamic mechanical stimulation of cell monolayers with direct optical access. The proposed IPMC platform employs a layered microfabrication strategy that allows precise tailoring of electrode geometry while preserving optical transparency across selected regions of the actuator. This design overcomes a key limitation of conventional IPMCs, namely their inherent opacity and resulting lack of (bio-)opto-mechatronics compatibility, thereby facilitating in vitro applications and real-time optical and fluorescent microscopy. The actuators are integrated into standard 12-well culture plates through customized mechanical and electrical interfaces and are driven by a compact, programmable electronic control system, enabling flexible modulation of actuation dynamics within biologically-relevant regimes. We confirm the biocompatibility of the platform by culturing Human Embryonic Kidney (HEK) cells and contractile cardiomyocytes from human-induced pluripotent stem cells (hiPSC-CMs). Together, these advances establish a scalable, low-voltage, and optically-compatible actuation platform for organ-on-chip and mechanobiology applications.
Engineered heart tissues (EHTs) formed around flexible pillars are used to measure the contraction force of myocytes. When based on cardiac cells derived from human induced pluripotent stem cells (hiPSCs), EHTs capture human cardiac physiology and drug responses in vitro. However, variability in contractile function often arises due to variation in tissue positioning on the pillar. Here, novel tapered pillars are introduced to achieve spatial confinement of tissues in EHT devices. The devices are fabricated by moulding polydimethylsiloxane (PDMS) into micromachined tapered cavities of a silicon substrate. The symmetrically-tapered geometry, with the minimum cross-section at the pillar mid-height, restricts tissue movement outside of the indented area. This increases sensitivity and accuracy of tissue contractile readout, providing high reproducibility with reduced variability between data points. Design and stiffness of tapered pillars are investigated to determine the optimal mechanical environment, obtain accurate contractile measurements, and achieve long-term culture of EHTs. Results show that tapered pillars provide superior confinement efficiency (over 90%) compared to straight pillars (30%), with tissue confinement directly correlated to pillar geometry rather than stiffness. The optimized precision in force readouts and long-term tissue studies enables higher sensitivity in the detection of contractile responses to drugs or diseases.
Human heart tissues grown as three-dimensional spheroids and consisting of different cardiac cell types derived from pluripotent stem cells (hiPSCs) recapitulate aspects of human physiology better than standard two-dimensional models in vitro. They typically consist of less than 5000 cells and are used to measure contraction kinetics although not contraction force. By contrast, engineered heart tissues (EHTs) formed around two flexible pillars, can measure contraction force but conventional EHTs often require between 0.5 and 2 million cells. This makes large-scale screening of many EHTs costly. Our goals here were (i) to create a physiologically relevant model that required fewer cells than standard EHTs making them less expensive, and (ii) to ensure that this miniaturized model retained correct functionality. We demonstrated that fully functional EHTs could be generated from physiologically relevant combinations of hiPSC-derived cardiomyocytes (70%), cardiac fibroblasts (15%) and cardiac endothelial cells (15%), using as few as 1.6 × 104 cells. Our results showed that these EHTs were viable and functional up to 14 days after formation. The EHTs could be electrically paced in the frequency range between 0.6 and 3 Hz, with the optimum between 0.6 and 2 Hz. This was consistent across three downscaled EHT sizes tested. These findings suggest that miniaturized EHTs could represent a cost-effective microphysiological system for disease modelling and examining drug responses particularly in secondary screens for drug discovery.