Impact of Regenerative Biology and Tissue Engineering Research

Presenter: Emily
Guest: Dr. Matthew Wheeler
Guest Bio: Dr. Matthew Wheeler , University of Illinois Department of Animal Sciences and member of the Regenerative Biology and Tissue Engineering Research Theme at the Institute for Genomic Biology

Segment Overview
We discuss the ethics of the work, as well as the future goals of the research, and the impact of this kind of research on the future of medicine.


Health Professional Radio

Emily: You’re listening to Health Professional Radio. This is Emily and my guest today is Dr. Matthew Wheeler. He’s a professor in the Animal Sciences Department at the University of Illinois and he’s also a member of the Regenerative Biology and Tissue Engineering Research team at the Institute for Genomic Biology. We’ve been talking today about Dr. Wheeler’s work with 3D printing and large animal trials. Dr. Wheeler, thanks for talking to me today.

Dr. Matthew Wheeler: I’m happy to talk to you.

Emily: We’ve been talking a little bit about 3D printing in your work, the most recent project which I think is so exciting, where you’ve actually created an airway splint for an infant and he is now able to breathe.  This is a child who was born withtracheobronchomalacia and was actually needing to be resuscitated daily by doctors, and now he’s breathing on his own.  Tell me a little bit about how the information is being shared between the doctors and your department.  Are you now getting phone calls and emails from doctors saying, “Hey, I have this issue.”  How is that information being shared?

Dr. Wheeler: Actually, the initial paper was published in The New England Journal of Medicine.  We have some subsequent papers that are under consideration at the Journal of American Medical Association Otolaryngology subdivision.  So that’s how the scientific data is being shared and certainly the clinical aspect of this, Dr. Glenn Green of the University of Michigan who led the surgery team and actually is dealing with the human patient, is fielding a lot of those calls.  But certainly the team, as we get questions, depending on whether it’s a scientific issue or it’s a clinical issue, we route that information to the appropriate part of our team.

Emily: I see, and your belief is that although there are researchers at a number of institutions, Cornell comes to mind, certainly the University of Illinois is a forefront runner in terms of these large animal trials.  Your belief is that large animal research, specifically with pigs, is really the way to bridge that gap between science and medicine?

Dr. Wheeler: Certainly a lot of these medical breakthroughs have been tested in animals before they’ve been deployed to humans, and certainly it’s a very critical strategy in the continuing of biomedical research because you can’t develop technologies and therapies directly in humans because of certainly ethical issues involved there.  The pig is a great model because the physiology is very similar.  It has the same kind of digestive system that we do.  Its immune system is very similar to ours.

The organ size, the case of the young pig, the trachea is very similar to that in a human infant patient.  The heart, lungs, and kidneys are very similar in size.  So it’s actually a great model.  It’s probably the best non-primate model to test biomedical devices in some of these therapies.  The pig has a long track record over the years of really helping out medical science.  I mean insulin, heart valves, skin for burn victims.  So there’s a lot of very useful therapies that have been developed in the pig.

Emily: You mentioned the word ethical.  Are there specific ethics that are in question whatsoever with this research?

Dr. Wheeler: I don’t think so.  I mean certainly there are folks that are not very keen on using animals for research, but certainly I think in many of these cases where there is no other possibility to test and to prove the therapies and you can’t do a computer simulation and know if it’s going to work.  You actually have to implant some of the devices and see if they’re going to heal correctly, and if the size and the configuration and the confirmation is appropriate, and basically look to see, is there a rejection issue.


Certainly, you wouldn’t want to put one of these in a patient if it was rejected.  So I think there has been a lot of good work that’s been done with computer modelling but some studies, especially a lot of these surgical interventions, need to be tested in animals.  We’re very concerned about the welfare of our animals and they are taken care of.  I mean, the first pig that we did on our recent jaw surgery, I stayed at the farm overnight making sure that the pig had adequate pain relief.

So yeah, the animals are taken very good care of, and we go to great lengths to be sure that the highest ethics are followed.

Emily: That’s great to hear and of course, when you think about the parents of that boy whose life you essentially saved with your team, I think it’s a very honourable work that you’re doing.  I’m curious about … you’re using a material called, PCL to create your devices.  What do you know about that?

Dr. Wheeler: PCL is a biodegradable polymer and it actually has a lot of really good qualities.  Again it’s biodegradable and biocompatible.  It’s been used in human medicine, so it’s FDA approved.  One of the interesting properties is that it melts at 60 degrees centigrade, so it allows you to use a laser to actually form very complex structures out of the PCL.  You can also mix it with other things.  So for example, when we’re doing bone work, we can actually add calcium phosphate, which is the mineral portion of bone directly to the material.

So you can actually make a material that has already started to comprise or contain mineral that ultimately the bone cells will attach to and use the mineral to develop new native bone in the patient.  In our studies in animals, it lasts anywhere between 24 and 30 months and it’s completely resorbed or invaded by the native bone and replaced.

Emily: Wow.  And you’re currently doing research obviously to figure out what the long term viability of a device like the airway splint we’re talking about is.  What is it looking like?  What do you know?  If it’s 24 to 30 months, is that long enough for that person’s own body to regenerate a similar organ or a similar device?

Dr. Wheeler: Yes.  Again, that’s the question in some of these studies that we don’t know until we try.  So we’ve had animals on trial.  We did some jaw scaffolds and kept the animals about 18 months on the scaffolds, basically had … in those animals had actually been resorbed and replaced by native bone.  So I think the idea with the airway scaffold is that we’re not sure that it will be replaced by native cartilage.  But even if it’s connective tissue that is stiff, it will have the same effect in that case.

It’s a little bit different than when you’re using it in bone where you expect it to integrate into the bone and actually have the bone replace it.  For example the jaw, where you have to chew, so there’s a lot of pressure on the new bone, so it just depends on where it’s going to go.  For some of the things we envisioned like nose and ear cartilage, it may not … loading it with cartilage cells which is what we’ve done, we’re still waiting on some of the studies to find out.  Is it making new cartilage and is the cartilage similar to what would normally be there?

So I think there’s a lot of things that are in progress and still a lot of unknown questions but it’s been very promising.

Emily: And you’re hoping actually to be able to add stem cells to devices like this?

Dr. Wheeler: Yeah, and we have been doing that.  Actually we’re interested in using cells from the patients so there’s a lot of … stem cells have not necessarily gotten the best press over the years, and it’s been mainly focused on ethical issues of embryonic stem cells.  But in our studies we’ve been using adult stem cells so all of us have stem cells in a variety of our tissues that allow us to undergo the natural healing process.  So you may be familiar that we’ve been transferring stem cells from bone marrow forleukaemia patients and for anaemia for almost 50 years.

So the basis of that is that there are stem cells there that actually go and repopulate the new bone marrow and make healthy blood cells.  Well it turns out that there are also a similar kind of [inaudible 0:10:29] stem cells in bone marrow but also in adipose tissue and fat, if you will.  Those cells actually are heavily involved.  When you cut yourself, or if you break a bone or have some other kind of traumatic injury—a laceration—those cells actually mobilize and help heal injury.

So we’ve actually been doing a lot of work on that type of cells since about 2003, looking at how those might be used in therapeutic scenarios.  We have several papers that we published in the last couple of years that show that actually you can use stem cells from fat, if you will, to augment healing in the craniofacial skeleton, primarily in the mandible of the lower jaw using the pig as a model.  We’ve now incorporated those into studies of cartilage—so the nose and ear cartilage.  We have not yet done it with the tracheal stent but that’s on the list to do.

We’re going to do a partial jaw transplant later this week where we’re going to use stem cells or stem cells were used to make new bone in the implant.  So yeah, we have been employing them in different scenarios, looking at such things as how many cellsdo you need?  Do you need to push them towards bone or cartilage before you use them or can you put in cells that are basically a true stem cell that can make any tissue?  There’s a lot of— again questions unanswered but quite promising and we’re pretty excited.

Emily: And then this PCL scaffolding provides that vehicle to put the stem cells in place to be able to do the work that they’re going to do.  Is that too overly simplified?

Dr. Wheeler: No, that’s correct.  So in some cases where you can’t just put stem cells in like … so say for example, you have an injury where you lose a several centimetre piece of bone.  So there’s a gap there and so you might need something to fill that gap in while it’s healing, and so a scaffold would be a logical thing to put in there.  PCL is good because it has quite a bit of strength and you can manufacture it so that it would basically bear some of the load while it was healing.  But you can also add growth factors to the scaffolding and stem cells as well.

So you basically again provide scaffolds, cells, and signals for healing basically as one therapy, as one package.  So those are the kinds of things that we’re looking at.

Emily: Wow.  Is it realistic to expect that in 25 years, if I need a new kidney, I’m going to be able to have a 3D printed kidney that has been created from my own cells?

Dr. Wheeler: Certainly, 25 years is a long time scientifically.  I think you’re going to see dramatic improvements in that area.  It’s hard to say.  A kidney is a pretty complicated organ, but certainly there’s a bladder out there that has been reproduced by a patient’s own cells using artificial matrix and so, yeah.  I think you’re going to start to see more and more of those things happen.

Emily: Wow.

Dr. Wheeler: I would say it’s not impossible.

Emily: I love that.  So it sounds like you’re kind of in the middle of a body of work that is coming to you.  You’re involved in this research now and you’re not asking what’s next?  What’s next is just presenting itself as each trial appears.  Is that what’s going on?

Dr. Wheeler: Yeah.  I think we’re focused on the trials that we’re working on, but as any good research program, as you work along, you have additional ideas, additional potential therapies and how you can use the technology.  I think that’s what’s great about our team, having engineers and physicians and biologists and stem cell biologists and material scientists and veterinarian scientists.  I mean, I look forward to the next couple of days because I’m sure there’ll be three of four more ideas of projects to do by the time they get in the car to go back to Michigan.

Emily: Wow, exciting work.  Well thank you so much for speaking with me today.  You’re listening to Health Professional Radio.  This is Emily and my guest has been Dr. Matthew Wheeler, a professor in the Animal Sciences Department at the University of Illinois and a member of the Regenerative Biology and Tissue Engineering Research Team at the Institute for Genomic Biology.  Dr. Wheeler, thanks so much for your time today.

Dr. Wheeler: Yeah.  It’s been my pleasure.