3D Bioprinting Rebuilds the Human Heart

A new study describes a collagen scaffold tissue engineering technique that brings us one step closer to being able to three-dimensionally (3D) print a full-sized, adult human heart.

Developed by researchers at Carnegie Mellon University (CMU; Pittsburgh, PA, USA), the technique, called freeform reversible embedding of suspended hydrogels (FRESH), allows collagen to be deposited layer-by-layer within a the hydrogel support bath, giving it a chance to solidify in place before it is removed. Controlling the pH-driven gelation provides a 20-micrometer filament resolution porous microstructure that enables rapid cellular infiltration and micro-vascularization, allowing the fabrication and perfusion of multiscale vasculature and tri-leaflet valves.

The FRESH support gel is easily melted away by heating it from room temperature to body temperature after printing is completed, without damaging the 3D printed collagen structure or the cells. The 3D-bioprinted collagen scaffold can be used to engineer components of the human heart at various scales, from capillaries to a full organ, with high fidelity and function. For the study, cardiac ventricles printed using human cardiomyocytes demonstrated synchronized contractions, directional action potential propagation, and wall thickening up to 14% during peak systole. The study was published on August 2, 2019, in Science.

“Collagen is an extremely desirable biomaterial to 3D print with because it makes up literally every single tissue in your body. What makes it so hard to 3D print, however, is that it starts out as a fluid; so if you try to print this in air it just forms a puddle on your build platform,” said co-lead author PhD student Andrew Hudson, MSc. “We've developed a technique that prevents it from deforming. What we're talking about is the convergence of technologies in the areas of stem cell science, machine learning, and computer simulation, as well as new 3D bioprinting hardware and software.”

Collagen is an ideal material for biofabrication due to its critical role in the extracellular matrix (ECM), where it provides mechanical strength, enables structural organization of cell and tissue compartments, and serves as a depot for cell adhesion and signaling molecules. However, it is difficult to 3D-bioprint complex scaffolds using collagen in its native unmodified form because gelation is typically achieved using thermally driven self-assembly, which is difficult to control.

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