William R. Wagner, PhD

Director, McGowan Institute for Regenerative Medicine, University of Pittsburgh

Professor, Surgery, Bioengineering, and Chemical Engineering, University of Pittsburgh

Biography

Dr. William Wagner, PhD, is the Director of the McGowan Institute for Regenerative Medicine and a Professor of Surgery, Bioengineering, and Chemical Engineering at the University of Pittsburgh. Dr. Wagner is the Founding Editor and Editor-in-Chief of Acta Biomaterialia, which has quickly grown to be one of the leading journals in the biomaterials field. He is a past President of the American Society for Artificial Internal Organs (ASAIO; 2010) and has served on the Executive Board of the International Federation of Artificial Organs (IFAO; 2009). He is a fellow and former vice president of the American Institute for Medical and Biological Engineering (AIMBE; 2000) and has also been elected a fellow of the Biomedical Engineering Society (BMES; 2007), American Heart Association (2001), International Union of Societies for Biomaterials Science and Engineering (IUSBSE; 2008), and National Academy of Inventors. In 2009 he was selected as the Society for Biomaterials representative to the IUSBSE. He has served as Chairman for the Gordon Research Conference on Biomaterials: Biocompatibility & Tissue Engineering as well as for the First World Congress of the Tissue Engineering and Regenerative Medicine International Society (TERMIS). Recently, Dr. Wagner was honored with the 2018 Inventor of the Year award by the Pittsburgh Intellectual Property Law Association. He was selected as Chairman for the 2013 BMES Annual Meeting and recently served a 3-year term as TERMIS Chair of the Americas Region. His recognitions have included the 2011 Society for Biomaterials Clemson Award for Applied Research and the 2012 Chancellor’s Distinguished Research Award from the University of Pittsburgh. Dr. Wagner’s research has generated numerous patents and patent filings that have resulted in licensing activity, the formation of a company (Neograft Technologies), and University of Pittsburgh Innovator Awards in 2007, 2008, 2009, 2010, 2014, 2017 and 2018. Dr. Wagner received his PhD in Chemical Engineering from the University of Texas at Austin, and his BS in Chemical Engineering from The Johns Hopkins University.

Interview with Bill Wagner

“[Dialysis is] an area that’s ripe for revolutionary thinking. The basic concept is kind of like some orthopedic devices – it hasn’t really changed much. It has been evolving a little bit, but hasn’t really changed in a major way and it seems like the time may be soon for something big to happen.”

Read full transcript

Kassandra Thomson (KT): Tell us a little about your background and your roles in your current position.

Bill Wagner (BW): My training is in chemical engineering, and I’ve been at the University of Pittsburg since ’91, so almost 30 years. In my PhD research I studied thrombosis, and kinetics and mass transfer aspects of thrombosis. I was recruited to Pittsburgh as part of the artificial heart program to try to get a better understanding of the problem of thromboembolism that was facing the patients being supported by these ventricular assist devices. Over the years, that continues to be an interest area that has led to the development of coatings technology, studies to better model blood biocompatibility in large animal models, participation in the design of rotary blood pumps, and also looking at other aspects like driveline infection and biocompatibility issues surrounding circulatory support devices. That’s what I’ve been working on the longest. Then in the early 2000s we started to pursue biomaterial-based approaches for the same problem, end-stage heart failure, and looking at ways, short of a fairly aggressive blood pump implantation, that we could slow down the progression of the disease to delay the time where the blood pump or a transplant would be needed. That led to a number of different types of biomaterial families being developed that we mostly applied in cardiac, but also started applying them to blood vessels. Now we’re also doing heart valves and we’ve done some skeletal muscle work with those materials. From an administrative perspective, I’ve been directing the McGowan Institute for Regenerative Medicine for 8 or 9 years now. It’s a group of about 200-250 faculty members that are generally interested in the regenerative medicine field, and we broadly define that to include medical devices, tissue engineering, and biomaterials. That has led to one of my major emphasis areas, to get technology to patients. So understanding internally what the barriers were to generation and development of intellectual property within the university, putting resources into place and mentorship into place so that more of our investigators could move forward with technology, and then bringing to bear resources from philanthropy or from federal sources to support projects that specifically have the aim of commercialization and moving towards clinical trial. A couple of the areas that we are currently focused on are pediatric device development (we have a project with Children’s Hospital of Pittsburgh and Children’s Hospital of Philadelphia supported by the FDA), and a craniofacial technology development effort from NIDCR (with Michigan and Harvard) that is trying to get regenerative medicine technology for craniofacial application areas developed. More broadly within the institute we celebrate and try to highlight efforts where we spin out companies and generate intellectual property. We’ve spun out 32 companies from the institute in total.

KT: That’s exciting! It sounds like you will be a great fit for our board.

BW: Yeah, I hope so!

KT: With that background in mind, what particular areas of expertise do you bring to the table as a member of our Scientific Advisory Board?

BW: Some of the areas I know Buddy [Ratner] is passionate about, I share that passion, which is this ongoing challenge of trying to have synthetic surfaces that blood contacts and have that be tolerated at a level that leads to high quality of life for patients. What can be done, how can we leverage advances in technology, including in pharma (new anticoagulants, new anti-platelet agents), to allow us to have more freedom with what we’d like to do with medical devices? I think dialysis is an example of what I call “high surface area, long contact”. Artificial hearts and circulatory support devices are [other examples]. It’s a fairly aggressive contact of a relatively high surface area for a relatively long period of time, especially if it’s going to be a chronic device. Oxygenators are another area that I’ve worked in from a biocompatibility perspective, and it’s the same challenge. Right now in medical technology, we’re reasonably good at small devices for a chronic period (vascular grafts, one could argue heart valves, stents), things that are not too large of a surface area but are in chronically. And then we do fairly well with very large surface areas that are very acute, oxygenators being an example of that. If it’s bypass you’re on for maybe an hour or two and then you’re off, they can crank up the anticoagulation to get you through that period. But where you try to go to large surface area for a long period of time, you’re really pushing the limits of biocompatibility. Chronic oxygenator, chronic circulatory support, chronic dialysis – all of these would be in that tough quadrant where you’re trying to do both, and I think that’s an interesting challenge.

KT: In your list of challenges that you see we need to overcome in order to transform patient care in dialysis, you talk about chronic placement and infection risk, thrombogenicity and anticoagulation. What other challenges do you see particular to portable or wearable dialysis?

BW: If the notion is to try and keep a membrane or a membrane cartridge functional for as long as possible, that means you’ve got to deal with not just cellular fouling but protein fouling, so maintenance of that membrane functionality. If there’s going to be a chronic connection to the vascular system outside the body, I know from circulatory support the infection problem that’s associated with that. Of course it’s well-characterized with vascular access and vascular grafts becoming infected from repeated access, but if one tries to have a more permanent-type port, particularly in a fragile population, there’s always a problem with infection. Then thrombogenicity and anticoagulation, what I was just talking about with high surface area – you can do it for a short period of time by being aggressive with anticoagulation, but you’re not going to have the quality of life that you’d like to have with patients being able to walk around and ideally do higher activity things outside of the clinic. Finally, I think with dialysis it always comes up, the non-clearance associated function, the hormonal and other kidney-related function, how does one supplement or provide that?

KT: At the CDI we think one of the critical factors to success is that we have patient input on the technologies we’re developing right from the very beginning. In order to do that we have put together a Patient Advisory Board that we meet with quarterly, and we also have patients embedded on our engineering design teams. Do you see patient engagement like this as important to medical device design, and do you see it at this level very often?

BW: So I try to nuance that answer, because I think the answer would be “it depends”. I think one could argue with some devices it’s not as important because there are not many options for the patient (like stents, valves, grafts). But there are many other technologies where it’s clearly very important. I think there is a high level of awareness in industry that that patient voice, the customer voice, needs to be considered, and particularly when it’s a competitive marketplace. It’s a bit of a stretch, but hearing aids are an example of that. Manufacturers are very much competing on patient adoption, and the patient decision has a big influence. I think with dialysis the situation is there’s a complex system and there are lots of problems, there are lots of incompatibilities, and many of these have been documented and can be communicated to researchers. I think there are two really valuable aspects. One aspect, which is not to be underestimated, is the inspiration that comes to the investigators by interacting with the patients currently being treated with the technology and in need of that advancement. I’ve worked with the Armed Forces Institute for Regenerative Medicine for the past decade, and one of the things that we did regularly, particularly during Operation Iraqi Freedom and Operation Enduring Freedom, is we would go to Walter Reed, or we would have returning war fighters come and speak to us about their injuries and what their quality of life was like and what they really wished they could have, things that really bother them, things they would like to see. For example an amputee: of course they would like to have a functional new arm grown, but realistically if one could just get rid of the heterotopic ossification that is causing them all kinds of pain, that would mean the world to them. That kind of interaction personalizes it in a very powerful way for investigators at all levels, particularly trainees (graduate students, post-docs, people early in their career) – they can really add passion to the efforts. The second aspect is the power of diversity in terms of skill sets and life experiences and how the problem is being thought about. Someone who is, in this case, undergoing dialysis three times a week has plenty of time to think about this challenge they’re facing, and human nature being what it is, to think about “wouldn’t it be nice if” or “why can’t it be like this”. The fact that the individuals undergoing dialysis are coming from all kinds of backgrounds, all walks of life, you’re going to get a pretty diverse coverage of concepts. In that mix may be something that sparks the right direction you wouldn’t have otherwise predicted for a researcher to go down, that may ultimately have impact. I think that’s valuable. With our institute, we have a retreat every year, and one of the favorite features of the retreat is the first night we’ll have patient stories. So we’ll pick one area of research where there’s either a clinical trial going on or one of our technologies has reached clinical impact, or where we’re not there and there’s a clear need that’s not being addressed. It’s very motivational, always a favorite of all attendees.

KT: We’ve seen the same thing when we bring our patient advisors to meetings with our investigators to tell their stories and their perspectives, and you can see that it really does have that kind of impact. So thank you very much for that perspective. The last question I have is what are you most excited about as a new member of our CDI Scientific Advisory Board?

BW: I’m always excited about learning, I want to learn more about the nuances of the problem as they’re being pursued. I personally have not been involved in many of the aspects of dialysis. We did a project on a degradable stent for AV fistula maturation, and that exposed me most recently to some of the problems, but I think it’s an area that I’m anxious to learn more about and I always like to see progress and new ideas. It’s an area that’s ripe for revolutionary thinking. The basic concept is kind of like some orthopedic devices – it hasn’t really changed much. It has been evolving a little bit, but hasn’t really changed in a major way and it seems like the time may be soon for something big to happen, which would be nice to be a part of.

KT: Dialysis became a therapy in Seattle in the 1960s, and has not really fundamentally changed much since then. So we agree, it’s time.

BW: I remember – I’ve been active in ASAIO, and dialysis has always been very big there. When I was a junior faculty member, Willem Kolff would still come to the meetings, and I remember I had a poster on blood biocompatibility, and he came and read it all and asked me questions. I was incredibly in awe to be able to be talking to him. You think about the kind of radical thinking that he put into play when he did what he did to begin the movement towards what we now call dialysis, and the conditions he did it under, it’s pretty remarkable.

KT: That’s incredible. Thank you so much for your time and for sharing your perspectives on all of this.

BW: Thank you.