TCT Focus: Dr. Vladimir Mironov

What made you interested in medicine and research? Did you always want to be a doctor?

My mother, Lucy Kaltenberger, was in medical school in Russia, but due to Hitler's occupation, she was forced to evacuate to Siberia because she was of Russian-German ethnicity (Stalin was afraid that Russian-Germans would collaborate with Hitler, and so he deported and interned them in Siberia and Asia). She always dreamed of seeing her two sons as doctors. She believed that under any political regime there would always need to be doctors.

I decided to be a doctor when I visited the anatomical theater in The Ivanovo State Medical Institute for the first time where my brother was already a student. I didn't always want to be a doctor. I dreamed of being a painter, but my parents told me that it was a very risky profession and they did not want to see me as a painter.

Medicine, anatomy, microscopical anatomy and electron microscopy excited me. I wanted to know how human organs and tissues are structurally organized and how they developed. The first time I saw how fascinating the cell ultrastructure was under an electron microscope, I decided to be a biomedical scientist, not a clinical doctor. I started my electron microscopic research the first year of my medical school. We had a student scientific society called The Student Scientific Society of the Ivanovo State Medical Institute, and I eventually became president.

How and when did you first hear about ink jet printing organs?

When I heard a talk about ink jet printing for molecular patterning by Thomas Boland from Clemson University at a conference in South Carolina, I suggested that he must use living cells and call this technology organ printing. It took a lot of beer to convince him to do this. Eventually, I have come to realize that there are certain limitations of applying ink jet technology to 3D organ printing.

How long have you been working with this process and what breakthroughs have been made?

Three to four years. The first breakthrough paper was published in Trends in Biotechnology in 2003.1 The first presentations started a little bit earlier.

A major breakthrough was demonstrating that cell aggregates can fuse and behave as visco-elastic fluid in permissive hydrogel (PNAS paper), patent application on "bioink" and bioprinting technology, designing the first 3D bioprinter and printing living 3D structures of desired geometry. In more simple terms, we basically created the rings from fused cell aggregates.2

Can you describe how organ printing works?

Basically, you have a robotic hand capable of moving in an X-Y-Z direction and an automatic syringe (nozzle or dispenser) with living cells in hydrogel. The whole process is robotic or automatically controlled based on software or organ "blueprint."

Why did you choose to work with the kidney over other organs? Do you plan on working with other organs soon?

There are several reasons to choose the kidney as a target organ for developing bioprinting technology. First, it is probably the most complex and most beautiful organ in the human body. Second, there is an unmet urgent medical need. Seventy thousand patients with end-stage kidney diseases are waiting for a kidney transplant, sometimes for three years. Eighteen people die every day on this waiting list. Bioprinting of human kidneys can eliminate this waiting list once and for all. Third, the kidney at a microscopic level is a bunch of tubes and we know how to make tubes. Finally, as medical economic research has demonstrated, even if a printed kidney will cost $250K, it can save a lot of money for Medicare. Thus, printing kidneys can not only save human life and the cost of medical treatment, but it can also be a foundation for a profitable multibillion robotic biofabrication industry with a $50 to 100 billion market (if including other organs). We are working on several projects, but our first goal is to print the branched vascular tree. If we are able to print the intra-organ branched vascular tree, then we can eventually print and maintain virtually any 3D human organ.

What do you think has been your greatest obstacle for bioprinting human kidneys?

We have not engineered a human kidney yet. But I think that we have finished the conceptual design or the complete compelling vision of bioengineering the whole human kidney. A bioengineered human kidney will not look 100 percent like a natural kidney. Robotic and automatic bioassembly put certain technological restraints on this. The greatest obstacle for de-signing a bioengineered human kidney was re-ducing the complex en-gineering task of building a complete organ to building small modules and then figuring out how they can be integrated. It is crystal clear to me that a func-tional human kidney can be robotically assembled.

The next step is to transform the conceptual design into a series of realistic manufacturing processes and designing robotic biofabrication and bioassembly tools. Basically, we are talking about a kidney bioassembly line or a kidney bioassembly plant. Integration of manufacturing tools and processes at such a level of complexity with biological processes and using living cells and tissue modules has not been done before. It is both a challenging and an exciting task.

The main obstacle for realizing such an ambitious project is access to a significant amount of money and cross-disciplinary expertise. It could not be done by one person or by one lab. It must be the result of focused, carefully orchestrated work of a well-funded specialized multidisciplibary academic research center or a private company.

How has rapid prototyping affected the way that you work?

Let me say very boldly—rapid prototyping is inescapable for the future of tissue engineering if tissue engineers are serious about mass production, automation and the reduction of cost of tissue engineering products. Robotic biofabrication and robotic biomanufacturing are logical steps in the evolution of biomedical applications of rapid prototyping technology. I am reading a lot of books about rapid prototyping technology. I participate as a speaker at leading U.S and European conferences on rapid prototyping. I am building collaborative relationships with rapid prototyping companies. To put it shortly—rapid prototyping is the future of tissue engineering. Period. I do not know any serious scientist or tissue engineer who has solid arguments against this statement. It is just an obvious evolving reality. It is not science fiction at all—it is already happening. In the next decade we will see even more impressive and accelerated progress. Robotic biofabrication is basically a new emerging multibillion dollar biomedical industry. It is something on the interface of the medical device, rapid prototyping and biotech industry.

Did you have any experience with RP before?

I did not have any experience or professional training with rapid prototyping before, but now I am one of organizers of the First Certified Training Course in Robotic Biofabrication of biomedical application of rapid prototyping technology held this summer in Charleston, SC.

In essence, organ printing is the variant of biomedical application of rapid prototyping technology or robotic-aided dispension of biologically relevant material or "layer by layer" additive biofabrication. Thus, in order to make progress in organ printing technology, I had to learn a lot about rapid prototyping technology. I bought and read all of the books about rapid prototyping possible. I also visited several rapid prototyping conferences and rapid prototyping labs around the world. However, the best way to force oneself to learn something is by teaching or by organizing a training course, which I did.

Life-long education and learning is a normal part of academic business in recent time. Original acquired professional expertise must be continually extended, updated and upgraded. There is no more long life once determined and trained for a life profession anymore. Since there are scientific or technological problems, one must constantly acquire all the necessary expertise and knowledge to be an effective researcher or engineer and logically develop these problems or research in the technological field and in other situations. Basically, one must grow and evolve professionally parallel with the evolution of research or technological problems which one is devoted to.

What do you see for the future of rapid prototyping in tissue engineering? Do you see an end in sight and think that we will be able to rapid prototype organs in the near future?

The future of rapid prototyping in tissue engineering is very bright. I think that we will be able to print human organs not only in vitro, but eventually in vivo directly in the operating room. As former CEO of Intel Andy Grove wrote "Everything which could be done will be done." It is just matter of will, energy, investment, well-orchestrated multidisciplinary efforts and proper management. It is industry, not academy, that will bring printed living organs on the market and in clinical practice. I think tissue engineering is the first area where the old and most desirable dreams of rapid prototyping specialists such as transition from rapid fabrication to rapid manufacturing or a combination of additive and subtractive manufacturing will be implemented. In 2010, health care will be 20 percent of the U.S. economy. Economic considerations (cost of product or service) in tissue engineering must be an integral part of the intellectual challenge from the very beginning (even at stage of ideation) in order to develop a commercially successful tissue engineered product or service. Thus, biomedical application is a logical and reasonable way of further developing the rapid prototyping industry. The only way to establish large scale manufacturing of tissue engineered products is by using rapid prototyping technologies or robotic biofabrication. That is why robotic fabrication and organ printing is an inescapable future of tissue engineering.

What other projects are you currently involved with?

We have several projects from printing human ear implants to printing the branched vascular tree of the kidney. Our most important, ambitious and fully-integrated one is the Charleston Bioengineered Kidney Project. It is our "brand name" project.

You are leading the first World Bioprinting Congress on October 23 – 26 2007 in Honolulu, HI. What are your goals for conference?

Before the conference, we signed an agreement with Sheraton Waikiki and promised to bring at least 250 people to Honolulu. We needed sponsors, of course. The main goal of this Congress is to bring together specialist from other fields and disciplines and create a new community and organize the World Academy for Bioprinting. The next step is to create a journal called BioAssembly, which will publish papers both about natural and man-assisted bioassembly or directed self-assembly.

You are involved in some amazing research. What (if you can pick just one) is something that you are most proud of?

I am most proud that my university recognized our efforts and provided a grant to create the first Bioprinting Research Center. Being a finalist of the World Technology Award for the development of organ printing technology is also not bad. What makes me happy is to see how bioprinting has evolved and has attracted more and more committed and sophisticated scientists and engineers. Bioprinting technology is very pervasive and exciting technology. It is like planting a tree and seeing how it is growing. I am also very proud that we were able to launch the Charleston Bioengineered Kidney project. It proved that South Carolina scientists and engineers can compete on national and global levels and that South Carolina can be transformed into a high-tech state. By the way, the rapid prototyping company 3D systems, Inc. moved recently from California to Rock Hill, SC. One of the first rapid prototyping companies, BPM (Ballistic Particle Manufacturing), was also founded in Greenville, SC by Bill Masters. Thus, the State of South Carolina has a proud past, present and future in robotic fabrication.

Is there a particular research project that you hope to become involved with in the future?

I am 52 years old already. Thus, before I will go to another world, I will have to see a printed human kidney successfully transplanted into a human; that would be more than enough to justify my life efforts and society resources invested in my training and my research. The man who first transplanted a kidney in 1954 received a Nobel Prize in 1970. It took 16 years for the Nobel Committee to realize the value of this medical breakthrough. Even if our group was successful, I am not sure that I will be able to live long enough to get a Nobel Prize due to the obvious time limit, but at least to finally see a successful outcome would be great. If somebody can do it faster than our group it will be great. This is the unique case when "lose" means "win"… at least for patients. I welcome any competitors in any place of the world to join us in this Nobel (in both senses) race. It would be nice to have some sort of X-Prize for printing a human kidney. TCT

Dr. Vladimir Mironov is the vice president of The World Academy for Bioprinting, associate professor of the Department of Cell Biology and Anatomy and director of the Bioprinting Research Center at the Medical University of South Carolina (Charleston). To learn more about his work, visit the Web site at www.musc.edu/bioprinting/index.html.