A growing area in the field of tissue engineering is the development of tissue equivalents as model systems for in vitro experimentation and high-throughput screening applications. Although a variety of strategies have been developed to enhance the structure and function of engineered cardiac tissues, an inherent limitation with traditional myocardial patches is that they do not permit evaluation of the fundamental relationships between pressure and volume that characterize global contractile function of the heart. Therefore, in the following study we introduce fully biological, living engineered cardiac organoids, or simplified heart chambers, that beat spontaneously, develop pressure, eject fluid, contain residual stress, exhibit a functional Frank-Starling mechanism, and generate positive stroke work. We also demonstrate regional variations in pump function following local cryoinjury, yielding a novel engineered tissue model of myocardial infarction. With the unique ability to directly evaluate relevant pressure-volume characteristics and regulate wall stress, this organoid chamber culture system provides a flexible platform for developing a controllable biomimetic cardiac niche environment that can be adapted for a variety of high-throughput and long-term investigations of cardiac pump function.

The therapeutic potential of mesenchymal stem cells (MSCs) for restoring cardiac function after cardiomyocyte loss remains controversial. Engineered cardiac tissues (ECTs) offer a simplified three-dimensional in vitro model system to evaluate stem cell therapies. We hypothesized that contractile properties of dysfunctional ECTs would be enhanced by MSC treatment. ECTs were created from neonatal rat cardiomyocytes with and without bone marrow-derived adult rat MSCs in a type-I collagen and Matrigel scaffold using custom elastomer molds with integrated cantilever force sensors. Three experimental groups included the following: (1) baseline condition ECT consisting only of myocytes, (2) 50% myocyte-depleted ECT, modeling a dysfunctional state, and (3) 50% myocyte-depleted ECT plus 10% MSC, modeling dysfunctional myocardium with intervention. Developed stress (DS) and pacing threshold voltage (VT) were measured using 2-Hz field stimulation at 37°C on culture days 5, 10, 15, and 20. By day 5, DS of myocyte-depleted ECTs was significantly lower than baseline, and VT was elevated. In MSC-supplemented ECTs, DS and VT were significantly better than myocyte-depleted values, approaching baseline ECTs. Findings were similar through culture day 15, but lost significance at day 20. Trends in DS were partly explained by changes in the cell number and alignment with time. Thus, supplementing myocyte-depleted ECTs with MSCs transiently improved contractile function and compensated for a 50% loss of cardiomyocytes, mimicking recent animal studies and clinical trials and supporting the potential of MSCs for myocardial therapy.

For efficiently assessing the potential for grafted cells to repair infarcted myocardium, a simplified surrogate heart muscle system would offer numerous advantages. Using neonatal rat cardiac myocytes in a collagen matrix, we created thin cylindrical engineered cardiac tissues (ECTs) that exhibit essential aspects of physiologic cardiac muscle function. Furthermore, a novel cryo-injured ECT model of myocardial infarction offers the potential for the longitudinal study of mechanisms of cell-based cardiac repair in vitro.

This paper presents an electroactive and soft vibrotactile actuator based on a dielectric elastomer. The vibrotactile actuator is composed of an upper layer, an adhesive tape layer, a dielectric layer with bumps, and a lower layer. When a voltage is applied to the actuator, an electrostatic force created between the upper and lower layers pulls the upper layer down, compressing the dielectric layer. As soon as the applied voltage is released, the upper layer is quickly restored to its initial state by the elastic force of the compressed dielectric elastomer. Because two forces contribute to the actuation at the same time, the created vibration is sufficiently strong to stimulate human mechanoreceptors. When the applied voltage is removed, the upper layer and dielectric elastomer return to their initial shapes. We conducted experiments to determine the best weight ratio of polydimethylsiloxane (PDMS) and Ecoflex, and to quantitatively investigate the haptic performance of the proposed vibrotactile actuator. The experiments clearly show that the plasticized vibrotactile actuator can create a variety of haptic sensations over a wide frequency range.

Benzopyrene (BaP) is polycyclic aromatic hydrocarbon (PAH), and is chemically modified in the animal body to form a number of metabolites that may elicit a various toxicity. However, the effect of BaP on neuroblastoma differentiation has remained unclear. We have studied the effect of BaP on neurite outgrowth using human SH-SY5Y neuroblastoma cells induced to differentiate by all-trans-retinoic acid (RA). Whereas BaP, at a concentration of 1 μM, had no significant effect on the viability of differentiating SH-SY5Y cells, the neurite outgrowth of differentiating SH-SY5Y cells 48 h after BaP treatment was significantly inhibited. Treatment of RA-stimulated differentiating SH-SY5Y cells with 0.1-3 μM BaP resulted in decreased level of cross-reactivities with tissue glutaminase (TGase) antibody in a dose-dependent manner. To investigate the involvement of AhR signaling in the inhibition of neurite outgrowth of differentiating neuroblastoma cells by BaP, we used AhR antagonists, α-Naphthoflavone and CH223191. Cotreatment of α-Naphthoflavone (1 μM) to BaP-treated SH-SY5Y cells recovered the expression level of TGase protein up to 200% of control. Like α-Naphthoflavone, another potent AhR antagonist, CH223191 (0.1 to 1 μM) also recovered the inhibition effects of BaP on neurite outgrowth and TGase expression level of neuroblastoma cells. These results suggested that AhR signaling should be involved in the inhibition process of BaP on RA-induced differentiation of SH-SY5Y neuroblastoma cells.