Congenital: Fontan: Basic Science| Volume 159, ISSUE 5, P1980-1981, May 2020


Open ArchivePublished:December 18, 2019DOI:
      Dr Glen Van Arsdell (Los Angeles, Calif). Dr Yeung, I rise to congratulate you and your coauthors on your innovative work. I literally have no criticism. This is exactly what we should be doing as a Society, taking technology that's ready to be tested and trying to find a use for it. Obviously when you start something, there are problems to work out, and so really my questions are around how do you see this moving forward to deal with some of the issues that you saw.
      Your initial work was on an IVC venous system and then you have moved to a moderate pressure system with a demonstrated lower collagen content. Do you suppose there are some tissue engineering methods by which you can make this applicable to a systemic side, is that conceivable, and how would you go about that?
      Dr Enoch Yeung (Baltimore, MD). Thank you for your question. Actually, in our previous study of the implantation in a sheep model, the graft was made from PGA and PLCL, but in this experiment the graft was made from PSCL and also PLCL. We used PCL instead of PGA because PCL has a slower degradation profile, which can stay longer in the graft, and we hope that it can provide a better mechanical property to the graft in this study. And we used the same materials, PGA and PLCL, to create a graft in a high-pressure system in another large model animal. This paper is now in the review process.
      Dr Van Arsdell. When you look at the pictures, I know there is demonstration of neointima or endothelial formation, but it actually looks a little bit different. Do you have any thoughts about that and what you might be doing in the future to solve that issue?
      Dr Yeung. Thank you for your question and suggestion. We agree that actually the new tissue formation in the graft is not exactly as what we expected in the tissue remodeling. We believe that there was an ongoing tissue remodeling process in this experiment. We are now working on the same animal model with longer survival and longer follow-up. We are eager to see and also want to evaluate how the tissue remodeling in this neointima will be in long-term follow-up.
      Dr Van Arsdell. Thank you for innovative work and comments.
      Dr Yeung. Thank you.
      Dr John E. Mayer (Boston, Mass). I agree. I think this is really exciting. This is bringing several technologies together to be able to custom make a graft for a given patient.
      I have a few technical questions. One is how big are the fibers that you are printing, what is the fiber diameter?
      Dr Yeung. You are talking about nano fiber diameter, right?
      Dr Mayer. Very small. How many microns?
      Dr Yeung. I'm sorry, I don't remember the exact number, but I would like to come back to you with the exact number.
      Dr Mayer. The reason that I ask, and I think it is illustrative of a more general principle, is that we know that the cells are going to react quite differently depending on what the diameter of the fiber is that they attach to, and since most cells are in the 10 to 20 micron size dimension, anything much bigger than that is going to be perceived as a flat surface rather than a fiber, which affects how the cells behave. This is one of the innumerable challenges in trying to design these kinds of grafts.
      As Toshi so kindly pointed out, we have been working in this field for over 20 years, and the only thing I can say with any degree of definitiveness is that the more you know the more you don't know. I think that's the real challenge for trying to devise a graft that can work in a very complicated biological environment. There is enough to keep another generation of investigators going, I would say, for sure.
      I do think another important question is whether or not we start decorating these fibers with chemical complexes so that you can then start guiding the cellular behavior more completely. Thank you.
      Dr Yeung. Thank you for your comment.
      Unidentified Speaker. One very quick question, just technical. Is the printer you use commercially available, or is it designed to print the particular polymers that you are using?
      Dr Yeung. Actually, in this experiment, all we used is PCL and PLCL, but with the same printer we can do another printing, use the same initial printing, or with another nano polymer.
      Unidentified Speaker. So is this a commercially available printer or is it a custom-made printer for your project?
      Dr Yeung. It is a kind of custom-made 3D printer, because as you can see, our graft is branched. We have to adjust how we can do the electrospinning. It is not common that the commercial 3D printer can do the branched 3D printing.