3D Bioprinting – Enabling Drug Discovery and Development and Cell Based Therapies

Sponsored by: Izumi International, Inc.

Introduction

Bioprinting is now a word most people have heard of, but might not really understand. Because there is a lot of hype regarding what is possible and what has already been accomplished, the term likely conjures up images of Frankenstein, a mouse with an ear growing on its back, glow-in-the-dark animals, or cyborgs.

The industry 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.

In this Ask the Expert session Katie Golson of Izumi International, Inc. will be answering your questions about 3D bioprinting and about how to apply this cutting edge technology to your drug discovery and development programs.

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Question 1

Are there any other technologies on the horizon that you think might be big in bioprinting in the future?

Yes. I believe acoustic dispensing will be a very big player in this industry, as it allows for much higher resolution than any syringe-based model. It is also very fast and accurate, and I believe it is gentle on cells so their viability remains high. It is a noncontact method, too! Another technology that could … Continued

Question 2

Are there any causes for concern, or at least areas of skepticism, about what bioprinting can or should accomplish?

Yes, of course there are, as with any new technology. Though dispensing methods might not be new, the applications we are seeing haven’t been done until now. Printing with live cells and biological reagents definitely requires not only a lot of caution on the part of the researcher, but it opens doors to regulatory questions … Continued

Question 3

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!

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 … Continued

Question 4

We have investigated 3D tissue culture of stem cells in wells for high throughput drug screening and toxicity testing. Can you tell me how 3D bioprinting for these would compare?

Without information on the equipment and materials you’re using (What is the medium that provides your cells with an extracellular matrix-like environment? How are the cells being dispensed, etc?), it is hard to say how bioprinting would compare with what you are currently doing. Bioprinting encompasses a wide range of technologies for depositing cells and … Continued

Question 5

What are the biggest challenges to being able to print organs?

Moving beyond the adherent 2D culture, building cells up in any 3D geometry means you must keep the cells alive. As the volumes we are attempting to construct get thicker than about 200um, we will have to somehow address the innermost cells and keep them healthy. If you have ever done cell culture, you might … Continued

Question 6

How long does it take to print tissue, could you give some examples?

As The Cell Culture Dish has reported in the past, bioprinting isn’t just about the act of printing out a structure. A successful bioprinting process means that the cells will form higher order structures when given the time and the proper biochemical/environmental cues. As such, it isn’t the printing process that takes the most time. … Continued

Question 7

I am new to bioprinting, what kind of factors are important to developing a successful bio ink?

Material properties that allow for ease of dispensing (general printing logistics) should be considered, as well as properties allowing for the tissue to remain viable. That is, the material should be “printable” yet also provide structural integrity in a 3D form to maintain the physiological environment. As such, many medical implant companies are having to … Continued

Question 8

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

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 … Continued

Question 9

Can you explain the different dispensing techniques?

While you could organize this information in different ways, I think of it as the use of contact methods vs. noncontact methods of dispensing. Contact Methods (also referred to as “extrusion”, as one would extrude the material out from the tip of a pipette/syringe; the tip comes close enough to the substrate for the material … Continued

Question 10

In your lab do you see good reproducibility across different print jobs? How do ensure this for drug testing?

As long as you keep all variables consistent, this shouldn’t be a problem. It is very important to maintain proper environmental control. Also, you should use a high quality dispensing system with repeatability specs that meet your needs (repeatability both in the xyz motion as well as in the dispensing itself). For example, if the … Continued

Question 11

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

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 … Continued