Robert Tranquillo discusses Cardiovascular Tissue Engineering

Dr. Robert Tranquillo

VICTORIA, September 8, 2014 –To celebrate 30 years of ViVitro’s global leadership in cardiovascular device test services and products, ViVitro Labs interviewed Robert T. Tranquillo.  Distinguished McKnight University Professor and Department Head of the Biomedical Engineering Department at University of Minnesota, Dr. Tranquillo discusses his ground-breaking work on  engineering living tissue and his trusty SuperPump pulsatile pump, along with advice for cardiovascular device start-ups and future academic faculties. The Tranquillo Research Group project is featured in Annals of Biomedical Engineering, Vol. 41, No. 12, December 2013.

VL: How is the Tranquillo Research Group Cardiovascular Tissue Engineering project  progressing?

RT: A major focus of the lab currently is fabricating, characterizing, and using our completely-biological tissue tubes, which possess circumferential alignment and are decellularized before use, as vascular grafts and tubular heart valves (described in that ABME publication).  We have three inter-related preclinical studies ongoing to assess how these tubular heart valves will peform in the aortic position of adult patients and (using a frameless variation of the design described in ABME) the pulmonary position of pediatric patients.  

VL: What are the main benefits of tissue engineering?

RT: A short question with a long answer depending on who you ask!  The idea advanced by Laura Niklasson (Yale) whereby living engineered tissues are decellularized prior to implantation is particularly appealing because they become allografts if effectively decellularized, affording much greater clinical utility.  What also makes this approach attractive is the high propensity of host cells to recellularize the resulting extracellular matrix, in contrast to decellularized native tissues.  This approach is actually a marriage of tissue engineering and regenerative medicine and could prove the superior approach for relatively simple connective tissues like vessels and valves.

VL: Your two million cycle bench-top durability performance is exciting progress.  How much durability testing would you define as appropriate in a bench-top setting for tissue engineered devices compared to current requirements for bio-prosthetic valves based on ISO 5840?

RT: A similar question!  We believe the ISO requirement is not relevant to our valve, assuming patient cells extensively recellularize the matrix and confer indefinite durability by virtue of their normal homeostatic maintenance of the extracellular matrix.  If that occurs within a month, as suggested by our preliminary data for arterial grafts (Syedain et al, TEA 20:11, 2014), it would correspond to a requirement of the acellular matrix valve tested in vitro to be only 2-3 million cycles (under quasi-sterile conditions so the unfixed matrix is not compromised by contamination – see below). 

VL: What is your current timeline for product availability?

RT: We have a concept more than a product at this point. If the aforementioned studies underway are successful, then it could be timely to start the process of generating a product. The most optimistic scenario would put a product 3-4 years out.

VL: You mention using the ViVitro Labs SuperPump pulsatile pump.  How are you able to test using a SuperPump pulsatile pump in the sterile environment required by cells?

RT: Since our valves are made from decellularized engineered tissue, we only need to minimize contamination to prevent degradation of the protein matrix, not to maintain viable cells.  In addition to periodic changes of the antibiotic-containing PBS test fluid, we implemented periodic exposure of the fluid reservoir to UV light.  This appears adequate.

VL: Your SuperPump pulsatile pump is nearly 15 years old.  How is it holding up?

RT: It is holding up better than the PI! It has needed servicing a couple times, which has always been prompt and effective, but it still continues to function well and reliably despite our “off-label” use for durability testing as well as for performance assessment.  We do not want to temp fate, so we are exploring options for a separate durability tester that would also allow for multiple samples.  

VL: Do you have any advice for cardiovascular device start-ups or future academic faculties interested in this area of research and development?

RT: It is a fantastic area for both R&D since a tissue-engineered heart valve is still not close to a reality.  As with any cell-based product, the time and cost must be carefully considered (if cells are part of the product fabrication – many are researching a product that never involves cells, utilizing only cell-compatible materials).  There is probably no easy answer or it would have been found by now, so one must be prepared for the long haul.  And the current options for adult prosthetic valves are very good, even though imperfect, so a tissue-engineered heart valve has to cross a high bar.  The converse is true for pediatric patients, who constitute a much smaller market but much greater clinical need.

Read more about Robert Tranquillo and the Cardiovascular Tissue Engineering project.

Read more interviews with Cardiovascular Pioneers.

Research by Dr. Robert Tranquillo using ViVitro equipment or services includes:

Development & Design of Improved Commissure for Tissue-Engineered Transcatheter Heart Valves

6-Month Aortic Valve Implantation of an Off-the-Shelf Tissue-engineered Valve in Sheep

Pediatric Tubular Pulmonary Heart Valve from Decellularized Engineered Tissue Tubes