Synthetic Extracellular Matrices for Tissue Engineering

Interview Questions for Dr. Kent Leach and David Mooney

• 1. What do you think holds the key to your success as researchers?

A driving curiosity about how things work, a desire to solve problems, and a short memory of criticism have been quite helpful. The scientific process of investigation and communication of findings is based on criticism and is often quite negative to new ideas, so obtaining real joy from your ideas and findings is crucial to forge onward over time.

• 2. What do you consider to be your key research accomplishments?

Two accomplishments to date that I consider to be quite important is our development of (1) technologies that enable blood vessel formation and function to be engineered via localized and sustained delivery of morphogens and cells (angiogenesis on demand), and (2) materials that regulate, via well defined molecular pathways, the fate of transplanted cells and greatly enhance their ability to form new tissues or regenerate existing, damaged tissues.

• 3. What was the turning point in your career?

(Mooney) I had the opportunity to work on the scale-up process for a small molecule drug while working at Dow Chemical. The idea that I could utilize my engineering abilities and training to help people and solve medical problems led me to graduate school and a career in the biomedical arena.

(Leach) While in graduate school, my advisor provided to me the chance to shift gears on my project and personalize it, perhaps to a greater degree than many of my peers. The exciting events which unfolded as a result of this opportunity fanned my research curiosity and eventually led me to an academic career in the biomedical and drug delivery area.

• 4. Who are the individuals who most influenced your research career?

(Mooney) There have been numerous individuals who had a great influence, but I will mention four in particular here. First, Robert Langer at MIT, from whom I learned to look at the big picture of my research, and to consider the potential of new ideas instead of focusing on criticism. Secondly, Joseph Vacanti of Harvard, who showed me the medical need motivating the field of tissue engineering, and provided a research environment in which I could mature scientifically during graduate school. Third, Donald Ingber, also of Harvard, who taught me most of what I know about the scientific method, and the need to be rigorous in one’s research. Finally, Robert Nerem of Georgia Tech, from whom I learned the importance of creating structures in which everyone benefits, and the power of collaborative efforts to accomplish big goals.

(Leach) Two individuals have had a tremendously positive influence on my career. Edgar O’Rear at the University of Oklahoma influenced me by granting space to excel independently while also encouraging me to keep in mind the engineering aspects of research. David Mooney of Harvard provided a research environment with countless opportunities to grow scientifically and professionally.

• 5. Pharmaceutical scientists are faced with the dilemma of having to publish in biomedical or basic science journals. Does it mean cutting edge science will not likely be featured in the Pharmaceutical Research?

The development of new technologies and ideas for therapies, while often driven by a medical need, frequently also provides new capabilities to address basic questions. Further, the multidisciplinary nature of the tissue engineering field necessitates that there is constant cross-talk between scientists, engineers, and clinicians of varied backgrounds. Pharmaceutical Research provides an extremely valuable vehicle for communication within this diverse audience, and we anticipate that both new technologies, and the fundamental questions that may be addressed with the new capabilities will be published in Pharmaceutical Research.

• 6. What are the challenges, and where is the field of Synthetic Extracellular Matrices for Tissue Engineering going? How do the articles in the theme section fill the gap?

Future advances in tissue engineering will likely require the development of matrices that can effectively serve a variety of roles, in place of the current generation of materials that more often simply bridge a defect. The rational design of matrices that can enhance tissue formation, whether by improving the mechanical and degradation properties or offering the potential to deliver tissue-inducing substances more effectively, is a critical focus of research. The articles within this theme section demonstrate that the appropriate selection or design of extracellular matrices can have a profoundly positive impact on cell behavior and tissue formation.

One of the major challenges facing this entire field is the development of a new vascular bed to support the metabolic needs of the engineered or regenerating tissues, and all three articles in this theme section address this issue. The development of large, conducting vessels, and networks of small distributing vessels are highlighted in this theme issue, as the ability to create both types of structures is absolutely critical to forming new tissues of any significant volume. In the future, technologies to create both types of vessels must be integrated to create complete vascular networks, and we anticipate this will be a major focus for the next few years.

• 7. What is the key to developing successful collaborative relationships?

All parties should bring something to the table, whether it is a specialized technique, novel biomaterial or bioactive factor, and both parties must benefit from the interaction. It is best if all parties are fully engaged in the project, and appreciate its various aspects.

• 8. What is your philosophy of educating graduate students?

We believe that the foremost goal of a Ph.D. education is developing the ability to perform independent research. To accomplish this, students must be given freedom to generate new ideas, and be provided a supportive environment that encourages their creativity and allows them to test their ideas. The advisor should help the student evaluate and develop their ideas (e.g., understand when an idea is ground-breaking versus incremental, and the difficulty in pursuing a given idea), and teach them how to effectively communicate their findings to the community.

• 9. What is the place for collaboration with industry in academia?

The tissue engineering field has historically involved considerable collaboration between industry and academia, and this has often driven progress in the field. Industry often has a better sense of the real problems facing a field, a better ability to translate findings to the clinic, and in certain fields has a better infrastructure to perform measurements than do academic labs. Academic labs will often, though, generate major advances in a field due to their ability to take a more fundamental approach to understanding the problem, and a broader view as to possible solutions. Collaborations between industry and academia can thus result in advances that neither party could make alone, and the fields of pharmaceutical research, biomaterials, and tissue engineering are ideal for these relationships to flourish. However, success depends on partnerships that combine the advantageous features of the two groups (e.g., problem input from industry with creative problem-solving in academics), and not subjugate one to the other (e.g., turning an academic lab into a fee for service enterprise solving minor problems for industry).