January 1, 2014

A new technology could revolutionize the medical industry by making it possible to manufacture whole organs such as livers, pancreases or kidneys ‘on-demand’, solving the shortage of organs transplant patients currently face. Although still in the prototype phase, the developers behind BioP3 technology have received a new grant from the National Science Foundation that will bring them even closer to automated organ printing.

The P’s in BioP3, developed by Jeffrey Morgan, a Brown University bioengineer, and Dr. Andrew Blakely, a surgery fellow at Rhode Island Hospital and the Warren Alpert Medical School, stand for “pick, place and perfuse”. The device adapts the “pick and place” principles used in the high-speed assembly of electronics, whereby components are picked and then precisely laid into place in order to form a whole.

In the case of the BioP3, the components used to build the living parts are 3D microtissues containing thousands to millions of living cells. The device picks up large, complex multi-cellular building parts, transports them to a build area, and precisely places the parts at a desired location while perfusing them (i.e. supplying the parts with a constant stream of fluid that either brings them nutrients or removes waste).

“For us it’s exciting because it’s a new approach to building tissues, potentially organs, layer by layer with large, complex living parts,” said Morgan. This process differs from 3D bioprinting, which has previously been thought of as the answer to creating human organs. That process involves depositing successive layers of cell-seeded material on top of another, printing one small drop at a time. “Our approach is much faster because it uses pre-assembled living building parts with functional shapes and a thousand times more cells per part,” said Morgan.

Morgan’s micromolding technique forms the microtissues by seeding cells into nonadhesive mirco-molds, where various types of cells self-assemble into predetermined shapes such as spheres, rods, donut rings or honeycomb slabs. With the BioP3 technology, which was introduced in a new paper in the journalTissue Engineering Part C, it will be possible to build even bigger tissues by combining the living microtissue components.

Within the BioP3 device, which looks like a small, clear plastic box, a selection of microtissues is stored in a central chamber. A nozzle, connected to various tubes and a microscope-like stage, is used to pick them up one at a time via suction. An operator can then move each component precisely to where it needs to be, gradually building up a 3D biological structure. The microtissues are enclosed in liquid, and the plumbing within the nozzle creates fluid suction, allowing the nozzle to pick up, carry, and release the living microtisues without doing any damage to them.

Overtime, the microtissues bond together, creating a single structure. “This project was particularly interesting to me since it is a novel approach to large-scale tissue engineering that hasn’t been previously described,” Blakely said.
The paper reveals several different structures created by Blakely, including a stack of 16 donut rings and a stack of four honeycombs. The honeycomb stack achieved a million-cell structure more than 2 millimeters thick, which is not quite enough cells to make an adult liver, but does prove that the stack has a density of cells consistent with human organs.

Honeycombs of bioengineered tissue can be stacked and arranged to build larger living structures. Image: Brown University

The BioP3 prototype was made mostly from parts available at Home Depot and cost less than $200, however because it is manually operated, it took Blakely one hour just to stack the 16 donut rings around a thin post. The developers are hoping to automate the process, thereby increasing the device’s speed and enabling it to independently and precisely assemble large-scale, high-density tissues.

Luckily, a $1.4 million, three-year grant from the National Science Foundation received in September will go towards automating the technology and will also fund more research into how large the living building parts can be made, how they will behave over long periods of time, and how their shape will evolve.

“We are just at the beginning of understanding what kinds of living parts we can make and how they can be used to design vascular networks within the structures,” Morgan said. “Building an organ is a grand challenge of biomedical engineering. This is a significant step in that direction.”


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