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The following is an interview with Prof. Sellke:

1. Can you tell me a bit about your background and what your research focuses on?
I grew up in Indiana and received my medical degree (MD) at the Indiana University School of Medicine. I trained in Surgery and Cardiothoracic Surgery at the  Indiana University Medical Center, NE Ohio University School of Medicine, and the University of Iowa. During my time at the University of Iowa, I did research with Dr David Harrison on microvascular physiology. I then moved to Boston, to Beth Israel Deaconess Medical Center, where I became Chief of Cardiothoracic Surgery at BIDMC, and to Harvard Medical School in 1990, where I became the Johnson & Johnson Professor of Surgery. I moved to Brown University in 2008 to become the Karlson & Karlson Professor of Cardiothoracic Surgery and Chief of CT Surgery. I recently stepped down from this position but continue to do research and some clinical work. My research focuses on the regulation of microcirculation in health and disease, especially in the setting of hypercholesterolemia, hypertension, and diabetes. I also investigate regenerative therapies for coronary artery disease, including stem cells, growth factors, and extracellular vesicles, and novel diabetic drugs.

2. What made you decide to publish a bioengineering article? Why did you choose Bioengineering MDPI?
It has a good reputation and has excellent peer review. The journal is easy to work with.

3. What was your experience publishing with Bioengineering MDPI?
We have published many articles with MDPI and Bioengineering.

4. Was it important to you that the journal is open access? How does open access publishing advance the field of bioengineering?
Open access increases readership and exposure.

5. What do you hope that readers will get from your paper?
We work in the area of regenerative medicine, extracellular vesicles for the treatment of CV disease, and we thought the journal was a good fit for our work.

6. What critical scientific or engineering problems did your research initially aim to address?Extracellular vesicles are derived from stem cells and may be a novel way to increase myocardial function and perfusion and alter oxidative stress, and improve cell signaling. Engineering EVs is one way to optimize the effect, potentially. Nearly all regenerative treatments of CV disease have failed in the clinical setting. Understanding how diabetes, medications, hypertension, and hypercholesterolemia affect these therapies is a focus of our lab. All of these illnesses increase oxidative stress in the myocardium, and this may be one of the factors causing a diminished response to all regenerative treatments.

7. What are the current bottlenecks in this field, and how did you identify your research’s breakthrough point?
Nearly all regenerative therapies, growth factors, gene therapy, cell therapy, and now extracellular vesicles work very well in otherwise normal animals such as the mouse or the pig, but nearly all therapies in patients have not worked. Understanding why myocardial regeneration is possible in mice and otherwise normal larger animals, and nearly always negative in clinical trials, is a bottleneck. Diabetes, aging, and hypertension all increase oxidative stress in the myocardium, and this may be one of the factors causing a diminished response to all regenerative treatments and why stem-cell therapies and other regenerative therapies have failed to meet expectations.

8. Which technologies or tools played pivotal roles in designing your methodology (e.g., AI, microfluidics, 3D bioprinting)?
We use physiological and clinically relevant models of human disease in rodents and especially pigs. We feel this gives us a large amount of clinically relevant information as to why, derived from normal, young animal models. We do not need the use of AI or 3D printing for our work, but it may become relevant in the future.

9. Have your experiments or theoretical models undergone significant adjustments? What motivated those changes?
We started using porcine models of hypercholesterolemia and diabetes about 25 years ago. This has been the major adjustment in our lab. We have tested many drugs and pathways in the myocardium to provide mechanisms for why therapies work or do not work.

10. Why do you think this article has been highly cited?
It provides a mechanism as to why the use of extracellular vesicles may offer some advantage in the treatment of myocardial disease.

11. Are there follow-up studies planned based on this paper’s findings?
We are continuing our studies using engineered EVs to improve efficiency.

12. Did your research involve cross-disciplinary collaboration? How did teamwork shape the outcomes?
I am a cardiovascular surgeon, and I work with molecular biologists, cardiologists, and other microvascular scientists to perform our research. It is definitely a multidisciplinary approach.

13. How did early career researchers or students contribute to this work?
We always have several postdoctoral fellows working in the lab. Indeed, the first author (Dr. Doug Harris) is a surgical resident from Harvard who intends to be a cardiovascular surgeon in the future.

14. What was the greatest technical or theoretical challenge during this research, and how did you overcome it?
There are many technical (surgical) issues with our experiments, and these can produce significant problems, but we have overcome most of these. The main issue is that we still do not fully understand why myocardial tissue regeneration has not worked well clinically.

15. Were there difficulties in data acquisition or experimental reproducibility? How were they resolved?
While there are some technical issues, reproducibility has not been a major problem as long as the experiments are carefully planned and variability is minimized.

16. Which technological directions in bioengineering deserve the most attention over the next 5 years?
We will continue to work on the use of novel medications and regenerative treatment for the management of CV disease.

17. How is AI reshaping bioengineering research in disruptive ways?
AI provides information that would otherwise be difficult to obtain in a rapid manner.

18. What learning resources would you recommend for newcomers entering this field?
Obtain a good knowledge of medicine and a medical degree so you can understand what is important and currently available clinically.