RF: Please tell us about your current work at TEMIM:
SR: The major focus of my research is cardiovascular mechanobiology. We’re trying to understand how regenerated tissues related to the cardiovascular system respond to mechanical environments. We study this in multiple ways: We try to understand the response of tissues themselves. How cells reform or change their shape or cytoskeletal structure in response to mechanical stresses. We evaluate in particular the utility of different stem cells to grow new cardiovascular tissues. A large focus is heart valve repair and replacement. We are currently investigating tissue engineering based strategies to repair or replace damaged heart valves. We have the ViVitro Pulse Duplicator unit in our lab to conduct functional assessment, so as to determine how well these tissues adapt to a localized hemodynamic environment once we have assembled them in a valve type format.
RF: How is the work going?
SR: In the last two years we’ve had a few string of successes, some have been published and a large part remains to be published and will come out in the next year. Among our major findings in the last two years, we’ve identified oscillatory fluid-induced stresses to be especially useful in regulating bone marrow stem cells towards a uniquely valve-specific lineage. However this can only occur if the magnitudes of these stresses are above some critical limit and it is possible that these magnitudes may need to be in the physiological range. At the moment, we’re hoping to fabricate valvular-shaped scaffolds and engineer tissues that can be tested for functionality. For that we’ll again be using the ViVitro Pulse Duplicator unit.
Other current events: we’ve been collaborating with clinicians from Joe DiMaggio Children’s hospital in Hollywood Florida. They’ve implanted a biodegradable material for valve replacement purposes in a few compassionate care cases. Engineered valves for repair or replacement are particularly needed among children with critical congenital valve disease because none of the prosthetics can grow with the child. Because of this very limiting issue the only feasible option, in theory, is to grow valves for the patient that will grow as the child grows. In a few compassionate care cases the physicians implanted these biodegradable materials which subsequently supported autologous tissue in-growth. At least in the short term, these patients continue to be well and the valves remain functional.
Why are the valves functioning well, will they continue to do so and can we make them better? To help answer these questions, as one strategy, we would like to use this biodegradable material as a scaffold to allow stem cells to grow and deposit a stem cell developed matrix. We’d like to then assess and quantify the functional effectiveness of these constructs using the ViVitro Pulse Duplicator unit.
RF: What are the reactions to this work?
SR: Well from the various projects in which the ViVitro pulse duplicator has been or will soon be utilized, I’d like to redirect to 2 projects. The first involves a collaboration we have with the University of Florida (UF). The collaboration was started off by a focus on a novel silicone valve prosthesis developed at UF. At FIU, we implanted these silicone valves into the ViVitro Pulse Duplicator unit and did a bunch of functionality testing; the results were published in the journal, JoVE, the Journal of Visualized Experiments. Subsequently the group at UF was interested in my stem cell approaches for valve repair. I also found the concept or repair refreshing and distinct from traditional intentions for tissue engineered heart valves for replacement purposes. Our discussions went back and forth to solidify our proposed approaches. After a year or so, we’ve forged their surgical, animal model expertise and clinical experience to our extensive experience in stems cells, bio-reactors and tissue engineering into grant applications to promote a strategy to use stem cells for valve repair work.
The other project relates to a US patent on a bio-reactor device that myself along with a team of inventors were recently awarded. This is a tool we use extensively in the lab. The focus is on being able to impart fluid flow stresses and cyclic flexure stresses and cyclic stretch. Flow, flex and stretch are the three main stresses for valves. The idea was to couple and decouple these stresses in any manner that we saw fit and in particular, be able to apply them at sub-physiological, physiological and supra-physiological levels. We can use any type of cell or scaffold materials to evaluate the mechano-biology response. We received interesting feedback from industry and academia. We published a few papers in the last year. One nice feature is that the device is MRI compatible. I anticipate many studies in my lab utilizing this device over the next couple of years.
RF: You mentioned the ViVitro Pulse Duplicator several times.
SR: I have already talked about how it has helped us in specific projects so now I guess I will provide a more general response – Well, It’s really the beginning as far as the Pulse Duplicator is concerned. There are many projects in which we would like to use the device but are limited by funding; but we are trying our best to secure grants and other sources of funding. Of course this goes beyond funding or testing, ultimately it is my sincere belief that these efforts will lead to better treatment options for the patient with critical valve disease. We cannot get there without all the fantastic people (collaborators, students, you guys at ViVitro!, etc) who are involved, and without carrying out the investigations that need to be done, but the reality is that none of this is possible without funding. I remain optimistic nonetheless. In the State of Florida, there continues to be interest by other groups regarding functionality for their valve prototypes and our lab does possess this expertise locally to be able to help them. As I already mentioned in one example, it originally helped us determine the hydrodynamic qualities of the UF silicone valve but more importantly it forged a strong collaboration between my lab and University of Florida Physicians, Surgeons and Veterinarians. So in this context, it has provided a base for people in the area to come to my lab and collaborate with me because they knew I had the equipment. This in turn has led to strong collaborations between our groups – this was certainly a big plus.
RF: What are your plans for the future?
SR: My vision is to try to engage in more rigorous cardiovascular engineering and cardiovascular regenerative medicine work. I would like to make this part of the country, that is, the State of Florida more in the forefront for these areas. For example, as large a population as we have in Miami and South Florida, there isn’t that much of a Cardiovascular Engineering or Regenerative Medicine focus. 15 years ago there were faculty engaged in cardiovascular work here, but that has somehow dissipated. I think there is a renewed interest that we don’t lose this important skill set. There is also a lot of industry interest locally as well. Establishing a cardiovascular institute in Florida that focuses on engineering and some of the cardiovascular mechano- biology and regenerative medicine/tissue engineering are some of my longer term goals.
RF: Do you have advice for our readers?
SR: Keep an open mind and learn every day. Have strong clinical and industry collaborators. Be persistent.
It’s important to keep an open mind. I think it’s easy to get caught up in your little cubicle and do what you’re doing. There are a lot of exciting things at the fringes of what you’re doing. You need to keep an open mind to accepting different approaches and learning something new every day no matter what career stage you are at.
Establish strong ties with clinicians and folks in industry. These are the people that are going to make a direct difference to the patient in terms of actual usage in the clinic and in commercial product development. Ultimately our goals need to translate to making better products for the patient. For example, it always amazes me how a 30 minute conversation with one of my Clinician friends leads to a string of new ideas – they face very specific set of challenges in the hospital. We as Bio-engineers need to be made aware of these problems and subsequently understand them in order to deliver a solution. Bio-engineers need to be on the same page as Clinicians as far as the next best treatment strategies are concerned. Clinicians have specific approaches that they know will have better outcomes if only one or two things were to be designed differently, used different materials or assembled differently, etc. If we want better treatments to translate more quickly, as Bio-engineers we need to deliver on that design, material or assembly but remain within the boundaries of the clinical approaches because that’s what the Clinicians are using today.
Be persistent – As with all big challenges in life you have to be patient and persistent. I subscribe to the idea that a success will arrive only after multiple “failures” but rather than to call them “failures” they are “building blocks” on the path to success. The key is to be aware from the very beginning that it’s going to be a long journey – it has probably been said before in different ways but essentially, “enjoy the journey more than that eventual success” which would be a healthy way of looking at it.
Read more interviews with Cardiovascular Pioneers.
Research by Dr. Sharan Ramaswamy using ViVitro equipment or services includes: