Whilst a number of groups have already demonstrated the use of 3D printing to build living tissue constructs in the shape of human organs these have lacked the cellular density and organ-level functions required for them to be used in organ repair and replacement.
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The new so-called SWIFT technique (sacrificial writing into functional tissue), developed by researchers from Harvard's Wyss Institute for Biologically Inspired Engineering and John A. Paulson School of Engineering and Applied Sciences (SEAS), is claimed to overcome that hurdle by 3D printing vascular channels into living matrices composed of stem-cell-derived organ building blocks (OBBs). The group, which reports its research in the journal Science Advances, claims that the process can be used to produce viable, organ-specific tissues with high cell density and function.
"This is an entirely new paradigm for tissue fabrication," said Wyss Institute researcher and co author of the paper Mark Skylar-Scott. "Rather than trying to 3D-print an entire organ's worth of cells, SWIFT focuses on only printing the vessels necessary to support a living tissue construct that contains large quantities of OBBs, which may ultimately be used therapeutically to repair and replace human organs with lab-grown versions containing patients' own cells."
SWIFT involves a two-step process that begins with forming hundreds of thousands of stem-cell-derived aggregates into a dense, living matrix of OBBs that contains about 200 million cells per millilitre. Next, a vascular network through which oxygen and other nutrients can be delivered to the cells is embedded within the matrix by writing and removing a sacrificial ink.
The cellular aggregates used in the SWIFT method are derived from adult induced pluripotent stem cells, which are mixed with a tailored extracellular matrix (ECM) solution to make a living matrix that is compacted via centrifugation. At cold temperatures (0-4°C), the dense matrix is soft enough to manipulate without damaging the cells, but thick enough to hold its shape - making it ideal sacrificial 3D printing. In this technique, a thin nozzle moves through this matrix depositing a strand of gelatin "ink" that pushes cells out of the way without damaging them.
When the cold matrix is heated to 37°C, it stiffens to become more solid while the gelatin ink melts and can be washed out, leaving behind a network of channels embedded within the tissue construct. The researchers were able to vary the diameter of the channels from 400 micrometres to 1 millimetre, and seamlessly connected them to form branching vascular networks within the tissues.
According to the group, tissues produced using the process remained viable, while tissues grown without these channels experienced cell death in their cores within 12 hours.
To see whether the tissues displayed organ-specific functions, the team printed, evacuated, and perfused a branching channel architecture into a matrix consisting of heart-derived cells and flowed media through the channels for over a week. During that time, the cardiac OBBs fused together to form a more solid cardiac tissue whose contractions became more synchronous and over 20 times stronger, mimicking key features of a human heart.
Commenting on the potential impact of the research Jennifer Lewis, a Core Faculty Member at the Wyss Institute, said: "Our SWIFT biomanufacturing method is highly effective at creating organ-specific tissues at scale from OBBs ranging from aggregates of primary cells to stem-cell-derived organoids. By integrating recent advances from stem-cell researchers with the bioprinting methods developed by my lab, we believe SWIFT will greatly advance the field of organ engineering around the world.
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