Dr. Carmine Gentile, PharmD/Ph.D., FAHA, received his BSc/MSc (Pharmaceutical Chemistry and Technologies) and PharmD at the University of Pisa, Italy and his Ph.D. in Biomedical Sciences (Cardiovascular) at the Medical University of South Carolina, Charleston, SC, USA, funded by a prestigious American Heart Association Fellowship. Since 2013, Dr. Gentile has worked in Australia at the Heart Research Institute, the University of Sydney, and now at UTS, supported by several awards and grants, working within a multidisciplinary team with scientists, industry partners, and clinicians to quickly translate his findings from bench to bedside. He currently leads the Cardiovascular Regeneration Group (www.gentilelab.com), working on 3D bioprinting and stem cell technologies for cardiovascular tissue applications both at the Kolling Institute/University of Sydney and UTS. He is a Senior Lecturer (Honorary) within the Sydney Medical School (Northern) at the University of Sydney and a Senior Lecturer (Faculty) within the School of Biomedical Engineering (Faculty of Engineering and IT) at the University of Technology Sydney. Dr. Gentile is an internationally recognized expert in the field of 3D bioprinting and stem cell technologies and his more recent studies focus on novel molecular and cellular approaches to treat cardiovascular disease, including myocardial infarction and heart failure. These studies are based on the use of vascularized cardiac spheroids or “mini-hearts” he developed as “bio-inks” for human heart tissues. In 2016, he was invited as Visiting Research Fellow at Harvard Medical School, where he worked towards novel in-vitro models using mini-hearts to study human heart physiology. Dr. Gentile will be speaking at the upcoming 3D Bioprinting for Cardiovascular System.
Jenny: When was the first encounter you had with 3D printing?
Carmine: My first exposure to 3D bioprinting in 2006 was even before 3D printing. After graduating in Italy for my studies in Pharmaceutical Chemistry, and a few months working as a pharmacist on a small island in the middle of the Atlantic Ocean (LaGomera, Spain), I was invited to the laboratory of Dr. Vladimir Mironov and Prof Christopher Drake at the Medical University of South Carolina (MUSC, Charleston, SC) for a month to explore this new project they were working on, the 3D bioprinting of blood vessels. The lab and the team were fascinating, very fast pace and populated with very visionary ideas for that time (the first publication about the concept of 3D bioprinting was from 2004). During my first visit for only one month, I had the opportunity to work with a multidisciplinary team of experts in bioengineering, medicine, and developmental biology, all working on recreating the vasculature typical of organs and tissues in the body for the first time in-vitro using 3D bioprinting technology. Following my first visit in January 2006, I then was offered a position as a research fellow to work within the team for two years, before I then decided to pursue a Ph.D. with my supervisor Prof Drake starting in 2008.
Jenny: What inspired you to start your journey in 3D Bioprinting?
Carmine: The first visit in 2006 was a mesmerizing experience. The ability to have 24/7 access to a laboratory to explore new emerging technologies and the continuing support and feedback by global leaders (we were working with Profs Glenn Prestwich and Gabor Forgacs, the founder of Organovo, to name a few) was extremely stimulating. I have to recognize it was my dream to work in a laboratory in the US while I was studying in Italy for my PharmD degree, and I was definitely making sure I was exposed as much as I could to all techniques available, as well as trying to become independent by fostering my critical thinking with the support of my supervisors. During that time we worked on embryonic stem cells (iPSCs were established a few years later only), new biomaterials, and a combination of cells all aiming at creating bioinks for the optimal formation of blood vessels in a test tube. Mixing, discovering, and traveling everywhere between the US and Europe for collaborations and conferences for my project was definitely a positive driver of my daily research in Charleston back then.
Jenny: Who inspired you the most along this journey?
Carmine: I still remember when I graduated in the US and my parents met my supervisor, Prof Drake. My mom told Chris “Thanks for everything, you have been his father while here”. And that was true. We were not simply working together in the same team, we created a family in our laboratory, where everyone was extremely supportive despite any challenges we had to face due to the nature of our innovative research. I still remember my supervisor waiting on his RO1 outcome, where basically he was able to pay for my colleagues and research until the beginning of the next grant. He was the most resilient person I have ever met, also making sure this was not a problem for us. I remember walking into his office and seeing a quote by Churchill on his wall, besides all the cover images his studies received (12 with my last publication in his lab), saying “Success is the ability to go from one failure to another with no loss of enthusiasm”. A quote very important for me.
Vladimir was the guy that believed in me while I had almost no experience in the lab by inviting me to the US in 2006. He has supported me from the very beginning, with all his capacity from day 1. He had a huge impact on my future career. My days with Vladimir were always characterized by fun activities while working hard in the lab nonstop. He would say “99.99% of what we do is not going to be successful, but that 0.01% is going to make you move forward in research”. Resilience was definitely one of the most important aspects I learned during my early days. And Vladimir would always make sure there was time to celebrate our accomplishments.
Finally, my parents have always been there for me to motivate me as well, always trying to find a way to make me feel comfortable with my decisions, including leaving home to pursue a career in science.
Jenny: What motivates you the most for your work?
Carmine: Thanks to the continuing support I received during my studies, I am trying to convey a similar message to my students. Indeed, my students represent one of my strongest motivations. Their passion for science is a constant driver of our work, and it is only by supporting them as much as I can that I can see them growing and becoming independent.
I would also like to highlight that cardiovascular disease patients are also my strongest motivation. I have had the opportunity to engage with patients through philanthropy events and following media releases about our research. It is a very unique feeling to be able to meet patients that may one day hopefully benefit from the studies from our team, while we continue to work hard to make sure that our findings can quickly translate from the bench to the bedside.
Jenny: What is/are the biggest obstacle(s) in your line of work? If you have conquered them, what were your solutions?
Carmine: The ability to establish and maintain a laboratory is a real challenge. This entails that you need people that believe in you, including your supervisors, students, and peers. In this process, creating a positive reputation is a long process and it can easily change. Having lived and worked on three continents, I had to face cultural differences, and I always tried my best at understanding the environment I have lived in with the maximum respect. That reflects also on your interaction with people and how you integrate your teammates into the group, how you deliver your research to other colleagues and to the public. For instance, grant writing was a completely different experience in the US compared to Australia, and only with lots of resilience and passion, you may receive the support you require, whether this means more funding for your research or any support from others.
Jenny: What do you think is (are) the biggest challenge(s) in 3D Printing/bio-printing? What do you think the potential solution(s) is (are)?
Carmine: To date, the most important technical challenges in cardiovascular bioprinting are the ability to create a patient-specific safe tissue capable of recapitulating the complex vasculature and contractile activity typical of the human heart. Not being able to achieve them both prevents the long-term survival of cells and the unwanted development of arrhythmic effects in the body.
It is also important to highlight that clinicians will eventually transplant a bioprinted tissue in a patient. Being able to establish collaborative networks with the clinical environment is critical for the success of this process.
We are also facing challenges in terms of regulatory bodies. As bioprinted cardiac tissues contain cells (including from the patients), they are differently regulated across the globe. The potential ability to develop a common regulatory pathway in several regional areas would facilitate our work with other laboratories globally to synergize clinical trials to validate our findings in animals.
Jenny: If you are granted three wishes by a higher being, what would they be?
Carmine: First wish: being able to live again the excitement of my days as a student;
Second wish: being able to travel faster between countries (Australia does feel very far away from other countries, even after years of living here);
My third wish: be able to do research for many more years with the same passion and support.
Jenny: What advice would you give to a smart driven college student in the “real world”? What bad advice you heard should they ignore?
Carmine: It is very simple: follow your passion! Students shouldn’t feel the pressure of doing what they don’t like. On the contrary, they should value themselves for their uniqueness. If something goes wrong with their project or relationship with the supervisor, that is not the end of the world, but it is important to move on. The world is full of opportunities, and it is important that the resilience that is required in this field is supported by the passion the student develops throughout the years by the support of family, friends, and team. Latins said “Homo faber fortunae suae”, meaning “every man is the Artifex of his destiny”, and it is important students can freely decide on their own future.