Magneto-acoustic protein nanostructures for non-invasive imaging of tissue mechanics in vivo.

Measuring cellular and tissue mechanics inside intact living organisms is essential for interrogating the roles of force in physiological and disease processes. Current agents for studying the mechanobiology of intact, living organisms are limited by poor light penetration and material stability. Magnetomotive ultrasound is an emerging modality for real-time in vivo imaging of tissue mechanics. Nonetheless, it has poor sensitivity and spatiotemporal resolution. Here we describe magneto-gas vesicles (MGVs), protein nanostructures based on gas vesicles and magnetic nanoparticles that produce differential ultrasound signals in response to varying mechanical properties of surrounding tissues. These hybrid nanomaterials significantly improve signal strength and detection sensitivity. Furthermore, MGVs enable non-invasive, long-term and quantitative measurements of mechanical properties within three-dimensional tissues and in vivo fibrosis models. Using MGVs as novel contrast agents, we demonstrate their potential for non-invasive imaging of tissue elasticity, offering insights into mechanobiology and its application to disease diagnosis and treatment.

Organoid engineering with microfluidics and biomaterials for liver, lung disease, and cancer modeling.

As life expectancy improves and the number of people suffering from various diseases increases, the need for developing effective personalized disease models is rapidly rising. The development of organoid technology has led to better recapitulation of the in vivo environment of organs, and can overcome the constraints of existing disease models. However, for more precise disease modeling, engineering approaches such as microfluidics and biomaterials, that aid in mimicking human physiology, need to be integrated with the organoid models. In this review, we introduce key elements for disease modeling and recent engineering advances using both liver and lung organoids. Due to the importance of personalized medicine, we also emphasize patient-derived cancer organoid models and their engineering approaches. These organoid-based disease models combined with microfluidics, biomaterials, and co-culture systems will provide a powerful research platform for understanding disease mechanisms and developing precision medicine; enabling preclinical drug screening and drug development. STATEMENT OF SIGNIFICANCE: The development of organoid technology has led to better recapitulation of the in vivo environment of organs, and can overcome the constraints of existing disease models. However, for more precise disease modeling, engineering approaches such as microfluidics and biomaterials, that aid in mimicking human physiology, need to be integrated with the organoid models. In this review, we introduce liver, lung, and cancer organoids integrated with various engineering approaches as a novel platform for personalized disease modeling. These engineered organoid-based disease models will provide a powerful research platform for understanding disease mechanisms and developing precision medicine.

Biphasic Electrical Pulse by a Micropillar Electrode Array Enhances Maturation and Drug Response of Reprogrammed Cardiac Spheroids.

Direct reprogramming is an efficient strategy to produce cardiac lineage cells necessary for cardiac tissue engineering and drug testing for cardiac toxicity. However, functional maturation of reprogrammed cardiomyocytes, which is of great importance for their regenerative potential and drug response, still remains challenging. In this study, we propose a novel electrode platform to promote direct cardiac reprogramming and improve the functionality of reprogrammed cardiac cells. Nonviral cardiac reprogramming was improved via a three-dimensional spheroid culture of chemically induced cardiomyocytes exposed to a small-molecule cocktail. A micropillar electrode array providing biphasic electrical pulses mimicking the heartbeat further enhanced maturation and electrophysiological properties of reprogrammed cardiac spheroids, leading to proper responses and increased sensitivity to drugs. On the basis of our results, we conclude that our device may have a wider application in the generation of functional cardiac cells for regenerative medicine and screening of novel drugs.