3-D Printers
That Really Cell


April 2013

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Any office worker knows workplace productivity hinges on the efficiency of your printer. Now cancer researchers are testing that technological truth in the laboratory, using a new 3-D bioprinting system to print living human cells and tissues for drug research.

Just as ink-jet office printers ran clunky dot-matrix printers off the road in the 1980s with their greater clarity, reliability, and speed, 3-D bioprinting may have what it takes to advance the painstaking drug development methods that rely on lab animals or traditional cell culture.

Developed by San Diego-based Organovo, the NovoGen MMX
3-D Bioprinter reimagines the concept of additive manufacturing for cell biology, using custom software and precise cell deposition technology to convert the cells of a clinical tumor specimen into a living, architecturally accurate model of human tissue. The idea is to help scientists find new drugs faster than the speed of cancer – without having to wait and wonder if they will work as well in humans as they did in mice.

In clinical use, bioprinting technology could allow doctors to use a patient’s own cancer cells in a laboratory setting to zero in on and test the best possible combination of drugs for a particular tumor in vitro – in time to stop cancer at an earlier, more treatable stage. But the first step is to develop laboratory models of bioprinted tissues that let drug researchers study the complex interactions of cancer cells and surrounding healthy cells up close and in proximity – in a representative microenvironment.

NovoGen MMX Bioprinter takes primary or other human cells and shapes them into 3D tissue. Image: Organovo.com

Technology: Inking the Deal

Widely available ink jet printing is the deposition of a layer of material (ink) on a substrate (paper) in user-programmable patterns (shapes, images, fonts). Named one of Time’s 50 top inventions of 2010, Organovo’s bioprinter uses the same idea, except the material is a quantity of human cells, also called “bioink,” a petri dish, transwell plate, or even a microscope slide act as the substrate, and the patterns are scientists’ computer-generated renderings of the tissue architectures they need to study. The cells come from tumor samples donated by current patients or from specimens preserved in a tumor bank – either way, the system requires only a source of cell material that can be grown and expanded.

The 3-D effect is achieved as the bioprinter stacks multiple patterned cell layers into a multilayer tissue. For larger structures, a co-printed hydrogel mold may provide additional support for the structure. From there, the principles of cell biology take over, and the individual cells grow together into a network of living tissue in a shape defined by the tissue engineers architecture and programmed design.

The idea of 3-D printing dates back 30 years, but has taken off rapidly as computational technology has advanced. Today 3-D printing in additive manufacturing and rapid prototyping is one of the tech industry’s hottest sectors. What the technology does for industrial materials, it can also do for biomaterials.

Three-dimensional bioprinting can produce tissue in shapes such as tubes or patches, with exciting potential in tissue engineering, organ regeneration, and wound control.

Organovo and CAD giant Autodesk announced an alliance in late 2012 to develop the sophisticated molecular design and simulation software required for engineering living systems. Scientist-friendly CAD programs would relieve researchers from writing and debugging code or having to hire specialized staff for the job. Although the companies have stated that full-fledged organs are far into the future, they anticipate there could be simple tissue-based products in clinical trials within a decade.

Meanwhile, applications like cancer drug testing are quietly taking the biomedical laboratory world by storm. In the field of cancer research, one of the first focus areas is the study of the chemical signals transmitted between cancer cells, how cancer growth is abetted by certain nearby cells, and how cancer might be vulnerable to drugs that manipulate these processes, says Joseph Carroll, Ph.D., an associate director at the Knight Cancer Institute at Oregon Health & Science University (OHSU, Portland, OR).

Clinical Impact: Tissues and Answers

“This could be very significant,” Carroll says. “We have never been able to examine this highly complex cellular signaling system in living human tissues before.”

The Knight team will initially use Organovo’s technology to test a promising pancreatic and breast cancer drug now under development with a private pharmaceutical firm. Carroll says the device will dramatically accelerate the proof-of-concept of this drug while potentially helping cancer patients at the institute who volunteer as study subjects. That’s why Organovo and OHSU have launched a formal collaboration to explore and fine-tune bioprinting approaches to novel cancer research.

“Animal models do not accurately represent human physiology, and the cell lines we use for research can’t show us how cells act in a native, three-dimensional architecture,” Carroll says, citing the statistic that about four out of five new drugs fail in clinical trials in part because of this knowledge gap. “This technology will give us a much more realistic model for discovering and testing cancer drugs. By studying the molecular mechanics of a tumor at the systems level – how the cells interact with one another and in the cellular microenvironment around them – we can learn how they grow and spread, and we can learn how to stop these processes.”

Michael MacRae is an independent writer.

We have never been able to examine this highly complex cellular signaling system in living human tissues before.

Joseph Carroll, OHSU Knight Cancer Institute

 
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by Michael MacRae, ASME.org