Artificial Liver : A Medical Revolution

Prof. Padma Rajagopalan is an Associate Professor in the Department of Chemical Engineering at Virginia Tech. She currently serves as director of the ICTAS Center for Systems Biology of Engineered Tissues.


TSA : An introduction to the field you work in. Where it stands today and what impact it could have on society.

PR : I work in the field of tissue engineering. The goal of scientists working in this field includes developing artificial organs that can be used inside the body, creating novel biomaterials, and designing mimics of the body’s organs and tissues. There are numerous applications of these research projects. Artificial organs can be used as transplants when the body’s own organs are diseased or damaged. Biomaterials can serve as scaffolds on which organs can grow. Such materials can also be instruments for delivering drugs to the appropriate tissue or cells. Mimics are useful for obtaining a fundamental understanding of how tissues work within the body. Examples of successes in this field include artificial skin, the dialysis machine, and regenerative medicine using stem cells. These successes attest to the positive, meaningful, and lasting impact that tissue engineering can have on almost all aspects of human health.

Tissue engineering is a young field. Scientists who work in it have a very diverse range of intellectual backgrounds: basic sciences including chemistry and biology, engineering disciplines such as mechanical, chemical, materials, and electrical, medical fields, e.g., surgery, pathology, stem cells, and cancer biology, and even more quantitative fields such as computer science and mathematics. Success in this field comes from collaborating with scientists in different fields, learning their “language”, and communicating your own expertise to them.

TSA : Something about yourself (I’m sure this will be of interest to students here). What your days and education at Kgp were like, how you moved into the area of Biomedical Engineering.

PR : I was born and brought up in the IIT Kgp campus, where my father Dr. P. K. Rajagopalan, was a professor in the Department of Electrical Engineering. I have very fond memories of our house A -7, our garden with its innumerable plants and trees, the beautiful campus, Durga puja, buying samosas at Golbazaar, and biking through campus while avoiding buffaloes. I went to school at St. Agnes and then at Kendriya Vidyalaya. I obtained an Integrated B.Sc./M.Sc. in Chemistry at IIT.

After I graduated from IIT, I obtained a Ph.D. from Brown University. My Ph.D. thesis was on Ion Containing Polymers. I followed my Ph.D. with a post-doctoral stint in polymer science at the University of Massachusetts, where I used supercritical fluids as means to modify polymer surfaces to render them useful in a number of different applications. Around that time, I heard several inspiring talks on the field of tissue engineering by leaders in this field. I became very interested and subsequently switched my research focus completely. I realized that I loved learning about cells and tissues (which I had not studied since high school) and working with and manipulating them. Fortunately, my background in polymer science has been very helpful in this field, since designing novel biomaterials is a critical component of tissue engineering.

TSA : About your work on the artificial liver. How your team went about developing it, an explanation of its working, and the scope. What does future work involve?

PR : The liver is responsible for converting foreign compounds that enter the body into less harmful chemicals. These include medicines, alcohol, cigarette smoke, and chemicals found in the environment. A region called the Space of Disse serves as an interface between endothelial cells and hepatocytes, which are the most important cell type in the liver. The vast majority of chemicals diffuse through the endothelial cells and the Space of Disse into the hepatocytes, where they are metabolized.

The liver construct we have developed mimics this part of the liver that interfaces with the blood vessels. When I was working at Harvard Medical School, I realized that I could use polyelectrolyte multilayers (PEMs) to separate these two cell types in such a way that the hepatocyte-PEM-endothelial cell construct mimicked the cellular structure found in the liver. At Virginia Tech, my group continued and refined this work. We have now been able to demonstrate that hepatocytes and endothelial cells are “happy” in each other’s company, especially when separated by the PEMs. We believe that the two types of cells exchange important chemical signals with each across the PEMs. Within our liver mimics, both cell types continue to maintain the function they normally perform within the body. We are now including other liver cell types in an effort to more closely mimic what is found in vivo.

We continue to design novel polymeric biomaterials to serve as scaffolds. We optimize mechanical, chemical, and surface properties to elicit optimal cellular responses. We are now using our livermimics to help us obtain insights into how the liver detoxifies foreign chemicals that enter the body, the effects of gold nanoparticles on liver function, changes in metabolic functions in the presence of toxins. Our research on the liver is supported by grants from the National Science Foundation, National Institutes of Health, the US Environmental Protection Agency, and the Jeffress Memorial Trust.

Another focus of my research is probing the effect of simultaneous and opposing cues on fundamental biological processes such as cellular sensing and locomotion. In 2010, I was awarded the prestigious National Science Foundation’s CAREER (Faculty Early Career Development Award) award to investigate these phenomena. In this project, we are designing polymer substrates that exhibit chemical and mechanical gradients in opposing directions to monitor cell migration.

I currently serve as a co-Director for the Center on Systems Biology of Engineered Tissues. The goal of the center is to define a new synthesis and synergy between tissue engineering and systems biology. My vision for the center is to seamlessly intertwine computational and experimental models to drive the next generation of advances in tissue engineering and in systems biology.

TSA : Lastly, any message you may have for our readers!

PR : When I was growing up, I thought that engineering and biology were distinct and incompatible fields. I have now learnt that it is possible to combine my love and fascination for both by working in tissue engineering!

 

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