Scientists Build Ventricle-on-a-Chip to Study Heart Disease

Ventricle-on-a-Chip

Scientists have made significant strides in using biomimetic tissue models to study human disease and development. However, replicating a fully functioning human heart in a lab has remained a complex challenge. To bridge this gap, a multidisciplinary research team has developed a miniature replica of a heart chamber, called the miniaturized Precision-enabled Unidirectional Microfluidic Pump (miniPUMP). This innovative device combines advanced stem-cell technologies with nanoengineering.

The miniPUMP consists of a tiny cylindrical scaffold created through precision 3D printing, serving as the framework for cardiac tissue made from human stem cell-derived heart muscle cells. This miniature heart chamber, mimicking the ventricle, beats spontaneously when submerged in cell media containing essential nutrients. Unlike previous methods that required electrical stimulation, the miniPUMP operates independently.

What sets the miniPUMP apart is its unique fusion of nanofabrication and tissue engineering. The nanoengineered components replicate various aspects of the heart, including chamber contractions, valve regulation, and metrics such as pressure and fluid volume, which were previously unrepresented in research literature. This advancement offers a more comprehensive model of heart function.

Miniaturization offers several advantages. It conserves precious stem cells and enables parallel experiments within a limited space. Furthermore, the mini heart chamber can be integrated with other organ-on-a-chip technologies, facilitating compatibility and broader applications.

The microfluidic chip, lined with living human cells, was created using a 3D-printing technique called two-photon direct-laser writing. Precision was crucial due to the miniature size of many miniPUMP components, smaller than a dust particle, and the entire device being no larger than a postage stamp.

One significant challenge was replicating the heart’s pumping function on such a small scale. The microengineered scaffold prevented the tissue from collapsing into a sphere. Additionally, sensitive pressure valves were required for directional fluid flow, which fine-resolution 3D printing achieved.

The mini heart chamber continued beating in the lab for three weeks, with potential for even longer durations with adjustments. This longevity and the replication of natural heart muscle contractions offer opportunities for drug development and testing, disease modeling, and advanced therapies like gene therapies.

Researchers can explore conditions such as hypertension and understand how the heart’s pumping mechanism changes over time. This knowledge can aid in developing therapies and treatments. Moreover, the miniPUMP could contribute to the study of human development during embryo development.

The miniPUMP project is part of CELL-MET, an NSF-funded engineering research center aiming to create functional heart tissue from a patient’s stem cells. Collaborating with researchers from Florida International University and Harvard Medical School, this project represents a significant step forward in tissue engineering and heart research.

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