3D Bioprinting as a tool for Drug Discovery and Cell Therapy Applications

By on March 8, 2016
Katie Golson

We recently finished our Ask the Expert discussion on “3D Bioprinting – Enabling Drug Discovery and Development and Cell Based Therapies”. During this Ask the Expert session, we discussed 3D bioprinting applications in the present and future. Specific topics included cell morphology, cell viability, reproducibility, dispensing techniques, bio ink properties with applications including printing tissues, printing organs and drug discovery methods.

3D bioprinting has come a long way from the time when researchers hacked into a desktop printer to experiment with printing out living cells. Researchers are now able to create vascularized tissue constructs that have proven viable when implanted into animals. This has opened a whole new area for cell based therapies and while printing of whole organs remains elusive (and probably won’t happen for many years), there are many applications for bioprinting that are commercially feasible and applicable today.

One of the most important healthcare applications for 3D Bioprinting that can be employed right now is in the area of pharmaceutical discovery and development. Pharmaceutical companies are faced with expensive, time-consuming, failure-prone clinical trials in order to get their drugs approved and on the market. A whole textbook could be written on why they are so expensive and risky, and companies must innovate their drug discovery and development processes. Izumi International, Inc. has been working with some of the top names in the pharmaceutical industry to optimize their drug discovery and production processes and incorporate bioprinting into their workflows. This will ultimately contribute to a much more streamlined and productive development framework, as the data generated from 3D assays vastly outperforms that from traditional 2D workflows.

This session was hosted by Katie Golson of Izumi International, Inc. With prior experience running automated liquid handling at Vertex Pharmaceuticals, Katie joined Izumi in 2014 as a Biomedical Automation Application Engineer where she helps develop customized laboratory automation and bioprinting solutions for companies and universities all over the world. She holds a Master’s in Bioengineering from University of California, San Diego and a Bachelor’s in Industrial Design from Georgia Institute of Technology.

Below is a sneak peek of the discussion, for a full transcript, please see – Ask the Expert – 3D Bioprinting – Enabling Drug Discovery and Development and Cell Based Therapies.

Question:

Do you see changes in cell morphology after printing and how do you assess this?

The Answer:

Yes, you do, and each printing technology and the printing parameters specified have varying effects. One way to visualize this is using DNA or membrane stains, as shown here.

For a pressure-driven system (syringe + needle), there is data that shows that varying the pressure generally has more effect on morphology change and viability than does varying the needle size, and there are even empirical models to predict the number of live/injured/dead cells according to these dispensing parameters.

Question:

What are some of the biggest factors affecting cell viability in 3D bioprinting. How do you preserve cell viability as much as possible?

The Answer:

There are many potential ways to injure cells during any bioprinting process, and each dispensing technology exposes the cells to varying degrees of these stresses. Some of these stresses include: Acceleration of the cells, pressure, thermal effects, shear forces, impact stresses, etc.

With pneumatic dispensing, the driving pressure and nozzle size can have an effect on the pressure (experienced by the cells) within the chamber, so using a lower pressure or a larger orifice could help lessen the damage.

Thermal effects should be minimized; avoiding biomaterials that require extreme temperature control or minimizing/localizing the thermal damage from the actual printing process (as in laser and inkjet systems).

Ensuring cells are provided nutrition/oxygen is also important, so if there are any long processes or delays, this could impact viability (for example, when cells are encapsulated within hydrogel layers that might require crosslinking, it could take some time).

Shear forces induced by the walls of the needles and impact forces should be reduced, and the surrounding matrix should provide enough structural support for cells yet still allow mobility.

These are just a few examples that will help increase viability in bioprinting methods.

Question:

How do you plan to get big drug companies on board with this new technology? Changing their workflows is going to be a massive undertaking!

The Answer:

That is a great question! We will start small. Many companies have “innovation” groups, or automation teams. These are the people that are currently looking at bioprinting and bringing 3D cell culture into the drug discovery and development workflows. I am working with them to get the dispensing technology that works for their particular material and their particular specs. Once we know which type of dispenser will work, we can begin to augment their current automation framework and integrate our components. We’ve done this in both bioprinting R&D labs as well as highly automated production environments.

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