In the fourth in her series on “What drives research in the field of biomaterials?” blogger Hamideh Emrani interviews Professor Kevin E. Healy at the University of California, Berkeley. You can catch up on Hamideh’s earlier interviews here.
I met Professor Kevin Healy at the University of California, Berkeley. He is the Jan Fandrianto Distinguished Professor in Engineering in the departments of Bioengineering and Materials Science and Engineering, and served as Chair of the Department of Bioengineering. As a pioneer in the field of bioengineering, Dr. Healy has won multiple distinctions and awards and has authored or co-authored more than 350 articles, abstracts and book chapters. He has received the 2011 Clemson award for outstanding contributions to basic biomaterials science and he is a named inventor on numerous panels and grant review study sections for the National Institutes of Health and international scientific agencies.
Dr. Healy’s highly multidisciplinary research lab designs and makes bioinspired materials to actively direct the fate of stem cells, and facilitate the regeneration of damaged tissues and organs. Major discoveries from his laboratory have centred on the control of cell fate and tissue formation in contact with materials that are tunable and adaptive in both their biological content and mechanical properties.
I met with Dr. Healy right after he had returned from a symposium honouring another distinguished biomaterials pioneer, Professor Molly Shoichet (University of Toronto).
With an emphasis on biomaterials and scaffold design, the projects in your lab have a range of applications in medicine, dentistry and biotechnology. What attracts you to these topics?
As I am sure is the case for many scientists, the main attraction is how research stimulates curiosity. But also, the clinical applications of our projects and the potential they have in improving the quality of life for a patient or treating a certain disease is very attractive.
Can you talk about bioinspired materials and their applications?
Overall, everything we do is based in biomaterial science. Bioinspired materials are materials inspired by nature and what nature has to offer. Our clinically translatable projects involve designing scaffolds to be used in tissue repair strategies, implant technology and microphysiological biosystems to be used for drug screening applications.
Our fundamental science projects focus on designing platforms for studying various cellular interactions, and development of well-defined cell culture protocols for potential therapeutic stem cell lines.
The microphysiological or organ-on-a-chip systems that we develop are applicable to drug screening. As an example, we make small cardiac microchambers that are meant to screen for the effects a certain drug has on early embryonic development. A pregnant woman might need to take drugs for allergy or mood disorders or more serious conditions that might affect the fetus or the development of the heart. Due to obvious reasons there are not going to be pregnant volunteers for most drug screen trials and our cardiac microchambers will provide valuable evidence for that.
Very interesting. Can you explain a bit more about the microchambers project?
During embryonic development, the most commonly reported birth defects involve the heart. And, determining possible side effects a certain drug might have on the heart development becomes really important. Currently, there are two-dimensional tissue culture assays to screen for drug toxicity. However, they are not able to predict how a certain drug can affect the early development of the three dimensional structure of the heart.
Cardiac tissue develops in looping structures, and our microchambers are basically small circles of chemically treated poly ethylene glycol (PEG) polymer films of up to 600 micrometers diameter. These have a specific coating to prevent cellular adhesion. We seed them with undifferentiated human pluripotent cells (induced pluripotent stem cells, iPSCs, or embryonic stem cells, ESCs) and go through the differentiation process.
After two weeks, the cells start to form a 3D pulsating structure, which we call the microchamber. Furthermore, based on where the cells are on this platform, they differentiate into different types of cells. Those cells in the middle form cardiac muscle cells and those on the periphery of the circle form collagen-producing fibroblasts. This “spatial differentiation” mimics the biologic development of the heart-in-a-lab setting.
Is it correct to say the shape of your designed platform plays an important role here?
Exactly. The confined geometry of the platform provides biochemical and biophysical cues to the cells that result in formation of a beating microchamber.
Are you working on similar platforms for other tissues?
For the drug screening projects we developed a heart-on-a-chip. We are also working on developing liver and adipose or fat-on-a-chip. The triad of these organs is really important for drug metabolism. Our ultimate goal is to integrate these systems in a multi-organ model for drug screening. Right now we have a functional system for cardiac and liver, and we have a chip for fat but with mouse cells.
And for the human projects you mostly use iPSC technology?
Yes. In the case of our heart and liver-on-a-chip project, we are using induced pluripotent human cells as our cell source. The beauty of these cells is that you can use the patient’s own cells and perform the drug screening experiments. We have essentially a single patient. Plus you can get patients with certain diseases and those diseases are going to be genetically encoded into their cells, which we then use to differentiate the cells into the tissue types of interest. This allows us now to have a disease specific approach to the problem.
A couple of significant discoveries happened and two of them recently in the last ten years. One was the iPSC technology developed by the Yamanaka group (2006) and the other was a novel genome editing technique by Jennifer Doudna (2015) who, interestingly, is located in our own building. The whole Cas9/CRISPR technology will really help out this field, even though it might not have been their target when they thought of those technologies.
With innovative tools of genome editing, we can make diseased cellular populations as controls for the drug screening projects.
What part are you more passionate about, and what is a main challenge in your field?
I think the most interesting aspect is the potential of finding a correct combination of stem cells and biomaterials to replace damaged or diseased tissue. However, it also becomes one of the main challenges. This is something that biomaterial scientists have been working on for almost 30 years.
Most stem cells die within a short period of time after being transplanted, especially in harsh environments such as the injured spinal cord or cardiac tissue. Thus, we will need to have the cells in a scaffold or matrix that will emulate the natural extracellular environment, protect the cells and help the cells to integrate into the host tissue.
For instance, in one of our projects, Amit K. Jha et al. show how relative concentrations of heparin added to a hydrogel scaffold can affect growth factor retention and, as a result, stem cell behavior. The correct combination of heparin and hydrogel resulted in sequestering the angiogenic (blood vessel forming) factors made by the stem cells within the matrix and formation of “vascular-like” networks within the hydrogel. Interestingly, this in turn helped with the challenge of keeping the stem cells alive; the cells were in close proximity to vasculature.
However, the difficulty is that you cannot say you have found a universal biomaterial for all stem cells. Different tissues will have different requirements and many details have to be optimized for the specific stem cell that you use and the purpose that it’s going to be used for.
What is your vision for the future of this field?
Traditionally, the main focus has been on designing scaffolds and optimizing transplantation of specific stem cells for purposes of repair and regeneration. That will continue. However, with the emergence of organ-on-a-chip, the biological assessment of cells in vitro would move from studying and characterizing a single cell towards assessing multi-organ systems and how they interact with each other in different physiological settings.
Do you have a specific message for young researchers/entrepreneurs?
I think there is a lot of potential for discovery and intellectual pursuits, in this field, from an academic standpoint. Yet, it is very translatable and certainly lends itself to investment by entrepreneurial spirits, VCs and angel investors. There is plenty to do, and being young and smart is a pretty good place to start.
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