Lab-Grown Teeth: The Future of Dentistry

0:00
Hey, good afternoon. I’m Dr. Joshua Green and my patients always ask me about lab grown teeth. I get this question all the time. So, I’m going to dive into the lit and try to bring everyone up to date.

0:14
Now, it’s an important topic for sure because tooth loss affects millions. People are living longer. Medications dry out their mouth. So, they’re losing teeth. Partial dentalism is on the rise.

0:37
Dental implants are great. You can’t get cavities on them but they can break and you can get periodontal disease around them. So you still have issues. Plus they don’t have any sensation. They don’t feel pain.

0:54
You can try to fix your teeth with crowns and root canals and fillings and whatnot, but even those solutions can run into problems and there’s a shelf life on many of them as well.

1:08
So, what are we going to do? These limitations have really driven scientists to try to find a better solution and that solution are bioengineered teeth. This is the holy grail.

1:22
And by the way, as a side note, some of the same people searching how to regrow teeth are also trying to regrow hair. So there’s a lot of money and there’s a lot of pressure to try to produce in this field.

1:34
But the idea is that teeth are supported by nerves and have a blood supply through the dental pulp. And they can sense pain, they can sense pressure, and to an extent they can even repair themselves.

1:57
And now the idea is, and this was a quote from the British Dental Association, that it’s exciting, but it’s a long way off. And I’ve really come to the same conclusion.

2:19
So the current estimates are 10 to 20 years and that may even be conservative.

2:25
So the first breakthrough, it really came on the scene back in 2009. This was Takahashi who was able to harvest these germ cells. This was on a mouse model that normally develop into a tooth.

2:42
And he was able to separate them into ectodermal and other types of stem cells, the mesoderm. They were able to mix them up and recombinate them. And they discovered that when those were re-implanted, it would create a tooth germ.

3:03
However, these are the ideal situations where you’re taking these stem cells that are already differentiated to form a tooth. Practically speaking, this isn’t useful in a human model.

3:23
Now, the result is in this mouse model, they were able to get a fully formed tooth, dentin, enamel, pulp, blood vessels, nerves. It could chew, it could feel pain. They were able to recreate this.

4:01
And there are stem cells, mesenchymal stem cells in bone marrow, like the kind in your jaw. So these stem cells are there. And if they’re in the right situation, they can begin to differentiate.

4:18
The real problem with this is it’s very difficult to get it to form an enamel that’s made by ameloblast cells. And those are specially differentiated ectoderm cells.

5:00
The real problem is a tooth is incredibly complicated. It’s a mini organ with several different types of tissues where the enamel actually grows outwards and the pulp grows back the other way.

5:36
Enamel, it’s the outer hard layer which is heavily mineralized. It’s acellular once it’s completely done. There’s dentin underneath which is much softer. It has dentinal tubules.

5:50
Finally, there’s pulp which contains the mechanisms to make more dentin and it can still grow inwards and it has nerves and blood vessels and even immune cells.

6:03
Finally, there’s the periodontal ligament, which is a fiber that basically goes all the way around the tooth, which is then surrounded in cementum, around the dentin, and it connects onto bone.

6:25
And that’s what provides the shock absorber that allows teeth to stay in our skeleton. It’s very strong. It works very well and gives you some proprioception when you push on the tooth.

6:56
So, a lot of what they’ve done, there’s a team at TUS that has come remarkably close by bioengineering teeth and pig jaws. Pig jaws being roughly the same size as ours.

7:17
What they had to do is use a decellularized germ from the pig jaw. They’re able to take that out. But in a way that’s cheating because it has all the information already set.

7:47
We actually transplant pig bone, pig tissues, pig hearts, all kinds of stuff or parts of pig hearts into humans all the time. Is it possible we could take a decellularized germ from a pig and put it in our jaw?

8:20
Now the scaffold, this is nature’s template. The idea is she removed all the cells from the tooth bud leaving only that matrix and that matrix is really what we would need to copy.

8:46
But how do we get this in a human? Once again, the ethical thing is human embryonic tooth bud cells are very hard to get ethically. You can’t really donate that kind of stuff.

9:22
Now, there’s very exciting breakthroughs. There’s many people working at this. King’s College in London, they’re making materials that are working on this. There’s been a lot of progress on making these types of artificial matrices.

9:44
They can be made out of gels, cellulose, whatever it is, some sort of thing that can resorb easily. Now, by the way, these still need to be surgically implanted. You can’t just put it on the outside and expect it to grow.

10:28
So really, there’s a couple of different options. Maybe it’s possible eventually to be able to grow a tooth in the lab and then transplant it. We may be able to grow it in the body and use our own stem cells.

11:00
Now, there’s a third idea that’s out there. These are actually in human trials in Japan. Very exciting stuff. There’s something called USAG-1, and it is a brake on tooth formation.

11:23
What’s exciting about that is that we actually have the potential to make a third set of teeth or perhaps even more than that. And this USAG-1 is a chemical that stops tooth development.

11:45
And by creating an antibody to it, they’re able to essentially suppress it. And when that happens, at least in animal models, those models start developing new teeth.

12:11
The problem is it’s not exact. You may generate a tooth in an area that you already have a tooth. You don’t generate every tooth. Younger people tend to generate more than older people.

12:48
Once again, the enamel challenge, the holy grail of tooth regeneration. Because it grows from a different type of tissue, it requires a highly specialized structure to grow.

13:15
Now for me as a dentist, I do a lot of crowns. So I don’t see a problem if you develop a tooth that’s got no enamel. I can just crown that tooth later and then that will essentially replace all the enamel on the tooth.

14:13
And one is Enamel Peptide actually. And what that is, is a simplified version of the protein amelogenin which is an incredibly complicated natural protein. So they were able to make a much more simplified protein.

14:56
But obviously, the issue is that it doesn’t make a particularly thick layer. We’re only talking about a couple of micrometers. It’s thin. It’s very liquid. So my hope is eventually it will be vastly improved.

15:29
Now, a lot of anytime you’re talking about incredible complexity, obviously machine learning, all these different types of things are incredibly influential in genetics, in medicine, protein folding.

15:56
So it’s exciting especially when you have a problem, a 3D problem of how you create a certain shape of a tooth. Can you create a scaffold for a certain cell? Can they do explorations of different proteins?

16:49
Now, again, it’s very exciting with this new drug in human trials in Japan, the USAG-1 we’re talking about. Even though that would only be at this time for people missing multiple teeth and you’re young.

17:28
But right now, we have different bits and pieces. We figured out how to grow ectodermal cells and we figured out how to grow dental pulps and various other mesenchymal cells.

18:17
At this time, there’s really nothing on the horizon that’s sophisticated enough to get a tooth that is at least developed enough to consistently go in a human. A lot of them are getting stuck at an early stage.

18:48
2035, 2045 I think as long as there’s a continued effort for it, this could certainly happen. I think it will happen. We just need to figure out the right recipe to make this work.

19:20
So, who’s going to benefit first? Obviously, right now we’re looking at people that don’t—kids, younger people that don’t have teeth and eventually adults with single tooth loss.

19:57
The reality is dental implants, which are titanium, are very good. Most options on the horizon will also require a surgery. So, the benefits are somewhat minimal.

20:32
The idea is that this certainly has potential and could be done in certain areas where you need to regrow bone and regrow soft tissue, which you can’t easily do with dental implants right now.

21:21
The changing role of dentists if this becomes reality in 20 years—which is something I may see in my career, I hope I do—is all of a sudden your role is going to be really understanding how this works.

21:42
You may have to wait for the teeth to grow. Implants often are not immediate, by the way. They require—I usually wait four months. A tooth that grows may take slightly longer than that.

22:23
So the idea is you may start regrowing teeth and managing that process which would be very exciting. I think we’d get some really good results for people.

22:53
Really the idea is that you could possibly just take a sample of cells from your gum which have the ability to form these dermal layers. Mesenchymal cells from your jawbone migrate towards that tooth bud and then your whole tooth would grow.

23:23
They figured out little bits and pieces of the puzzle, but nobody’s quite put it all together yet. And that is something that could be done. I think it’s on the horizon and will happen soon.

23:40
Hope you guys enjoyed this. I’ll be back again tomorrow in the morning at 6:00 a.m. live. Thank you very much.