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TEDGlobal 2013

Molly Stevens: A new way to grow bone

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What does it take to regrow bone in mass quantities? Typical bone regeneration -- wherein bone is taken from a patient’s hip and grafted onto damaged bone elsewhere in the body -- is limited and can cause great pain just a few years after operation. In an informative talk, Molly Stevens introduces a new stem cell application that harnesses bone’s innate ability to regenerate and produces vast quantities of bone tissue painlessly.

- Biomaterials researcher
Molly Stevens studies and creates new biomaterials that could be used to detect disease and repair bones and human tissue. Full bio

As humans, it's in our nature
00:12
to want to improve our health
and minimize our suffering.
00:14
Whatever life throws at us,
00:17
whether it's cancer, diabetes, heart disease,
00:19
or even broken bones, we want to try and get better.
00:21
Now I'm head of a biomaterials lab,
00:24
and I'm really fascinated by the way that humans
00:27
have used materials in really creative ways
00:30
in the body over time.
00:32
Take, for example, this beautiful blue nacre shell.
00:35
This was actually used by the Mayans
00:38
as an artificial tooth replacement.
00:40
We're not quite sure why they did it.
00:44
It's hard. It's durable.
00:45
But it also had other very nice properties.
00:48
In fact, when they put it into the jawbone,
00:52
it could integrate into the jaw,
00:54
and we know now with very sophisticated
00:57
imaging technologies
00:59
that part of that integration comes from the fact
01:01
that this material is designed
01:03
in a very specific way, has a beautiful chemistry,
01:05
has a beautiful architecture.
01:08
And I think in many ways we can sort of think
01:10
of the use of the blue nacre shell and the Mayans
01:12
as the first real application
01:15
of the bluetooth technology.
01:16
(Laughter)
01:19
But if we move on and think throughout history
01:20
how people have used different
materials in the body,
01:25
very often it's been physicians
01:28
that have been quite creative.
01:29
They've taken things off the shelf.
01:31
One of my favorite examples
01:33
is that of Sir Harold Ridley,
01:35
who was a famous ophthalmologist,
01:38
or at least became a famous ophthalmologist.
01:40
And during World War II, what he would see
01:42
would be pilots coming back from their missions,
01:44
and he noticed that within their eyes
01:47
they had shards of small bits of material
01:49
lodged within the eye,
01:52
but the very interesting thing about it
01:53
was that material, actually, wasn't causing
01:55
any inflammatory response.
01:57
So he looked into this, and he figured out
01:59
that actually that material was little shards of plastic
02:02
that were coming from the canopy of the Spitfires.
02:04
And this led him to propose that material
02:07
as a new material for intraocular lenses.
02:10
It's called PMMA, and it's now used
02:12
in millions of people every year
02:14
and helps in preventing cataracts.
02:16
And that example, I think, is a really nice one,
02:19
because it helps remind us that in the early days,
02:21
people often chose materials
02:24
because they were bioinert.
02:26
Their very purpose was to
perform a mechanical function.
02:28
You'd put them in the body
02:31
and you wouldn't get an adverse response.
02:33
And what I want to show you is that
02:35
in regenerative medicine,
02:36
we've really shifted away from that idea
02:38
of taking a bioinert material.
02:40
We're actually actively looking for materials
02:41
that will be bioactive, that will interact with the body,
02:44
and that furthermore we can put in the body,
02:47
they'll have their function,
02:49
and then they'll dissolve away over time.
02:51
If we look at this schematic,
02:55
this is showing you what we think of
02:57
as the typical tissue-engineering approach.
02:59
We have cells there, typically from the patient.
03:01
We can put those onto a material,
03:04
and we can make that material
very complex if we want to,
03:05
and we can then grow that up in the lab
03:08
or we can put it straight back into the patient.
03:10
And this is an approach that's
used all over the world,
03:13
including in our lab.
03:15
But one of the things that's really important
03:19
when we're thinking about stem cells
03:21
is that obviously stem cells
can be many different things,
03:23
and they want to be many different things,
03:26
and so we want to make sure that the environment
03:28
we put them into has enough information
03:29
so that they can become the right sort
03:32
of specialist tissue.
03:34
And if we think about the different types of tissues
03:36
that people are looking at regenerating
03:40
all over the world, in all the
different labs in the world,
03:42
there's pretty much every tissue you can think of.
03:44
And actually, the structure of those tissues
03:47
is quite different, and it's going to really depend
03:48
on whether your patient has any underlying disease,
03:51
other conditions, in terms of how
03:53
you're going to regenerate your tissue,
03:56
and you're going to need to think about the materials
03:58
you're going to use really carefully,
04:00
their biochemistry, their mechanics,
04:02
and many other properties as well.
04:04
Our tissues all have very
different abilities to regenerate,
04:08
and here we see poor Prometheus,
04:11
who made a rather tricky career choice
04:13
and was punished by the Greek gods.
04:16
He was tied to a rock, and an eagle would come
04:19
every day to eat his liver.
04:21
But of course his liver would regenerate every day,
04:23
and so day after day he was punished
04:25
for eternity by the gods.
04:27
And liver will regenerate in this very nice way,
04:33
but actually if we think of other tissues,
04:37
like cartilage, for example,
04:39
even the simplest nick and you're going to find it
04:40
really difficult to regenerate your cartilage.
04:42
So it's going to be very different from tissue to tissue.
04:45
Now, bone is somewhere in between,
04:48
and this is one of the tissues
that we work on a lot in our lab.
04:51
And bone is actually quite good at repairing.
04:54
It has to be. We've probably all had fractures
04:56
at some point or other.
04:58
And one of the ways that you can think
04:59
about repairing your fracture
05:02
is this procedure here, called
an iliac crest harvest.
05:03
And what the surgeon might do
05:06
is take some bone from your iliac crest,
05:08
which is just here,
05:11
and then transplant that
somewhere else in the body.
05:12
And it actually works really well,
05:15
because it's your own bone,
05:16
and it's well vascularized,
05:18
which means it's got a really good blood supply.
05:19
But the problem is, there's
only so much you can take,
05:22
and also when you do that operation,
05:24
your patients might actually have significant pain
05:27
in that defect site even two
years after the operation.
05:30
So what we were thinking is,
05:33
there's a tremendous need
for bone repair, of course,
05:35
but this iliac crest-type approach
05:38
really has a lot of limitations to it,
05:41
and could we perhaps recreate
05:43
the generation of bone within the body
05:45
on demand and then be able to transplant it
05:47
without these very, very painful aftereffects
05:51
that you would have with the iliac crest harvest?
05:56
And so this is what we did, and the way we did it
05:59
was by coming back to this typical tissue-engineering approach
06:02
but actually thinking about it rather differently.
06:05
And we simplified it a lot,
06:08
so we got rid of a lot of these steps.
06:10
We got rid of the need to
harvest cells from the patient,
06:12
we got rid of the need to put
in really fancy chemistries,
06:14
and we got rid of the need
06:17
to culture these scaffolds in the lab.
06:19
And what we really focused on
06:21
was our material system and making it quite simple,
06:24
but because we used it in a really clever way,
06:27
we were able to generate enormous amounts of bone
06:30
using this approach.
06:32
So we were using the body
06:34
as really the catalyst to help us
06:36
to make lots of new bone.
06:38
And it's an approach that we call
06:40
the in vivo bioreactor, and we were able to make
06:42
enormous amounts of bone using this approach.
06:45
And I'll talk you through this.
06:47
So what we do is,
06:49
in humans, we all have a layer of stem cells
06:51
on the outside of our long bones.
06:53
That layer is called the periosteum.
06:55
And that layer is actually normally
06:57
very, very tightly bound to the underlying bone,
06:59
and it's got stem cells in it.
07:02
Those stem cells are really important
07:03
in the embryo when it develops,
07:05
and they also sort of wake up if you have a fracture
07:07
to help you with repairing the bone.
07:09
So we take that periosteum layer
07:12
and we developed a way to inject underneath it
07:14
a liquid that then, within 30 seconds,
07:17
would turn into quite a rigid gel
07:20
and can actually lift the
periosteum away from the bone.
07:21
So it creates, in essence, an artificial cavity
07:25
that is right next to both the bone
07:28
but also this really rich layer of stem cells.
07:32
And we go in through a pinhole incision
07:36
so that no other cells from the body can get in,
07:37
and what happens is that that
artificial in vivo bioreactor cavity
07:40
can then lead to the proliferation of these stem cells,
07:45
and they can form lots of new tissue,
07:48
and then over time, you can harvest that tissue
07:50
and use it elsewhere in the body.
07:52
This is a histology slide
07:55
of what we see when we do that,
07:57
and essentially what we see
07:59
is very large amounts of bone.
08:02
So in this picture, you can see the middle of the leg,
08:03
so the bone marrow,
08:06
then you can see the original bone,
08:07
and you can see where that original bone finishes,
08:09
and just to the left of that is the new bone
08:12
that's grown within that bioreactor cavity,
08:15
and you can actually make it even larger.
08:17
And that demarcation that you can see
08:19
between the original bone and the new bone
08:22
acts as a very slight point of weakness,
08:24
so actually now the surgeon can come along,
08:26
can harvest away that new bone,
08:28
and the periosteum can grow back,
08:30
so you're left with the leg
08:32
in the same sort of state
08:34
as if you hadn't operated on it in the first place.
08:36
So it's very, very low in terms of after-pain
08:38
compared to an iliac crest harvest.
08:42
And you can grow different amounts of bone
08:45
depending on how much gel you put in there,
08:48
so it really is an on demand sort of procedure.
08:50
Now, at the time that we did this,
08:53
this received a lot of attention in the press,
08:55
because it was a really nice way
08:58
of generating new bone,
09:01
and we got many, many contacts
09:02
from different people that
were interested in using this.
09:04
And I'm just going to tell you,
09:07
sometimes those contacts are very strange,
09:09
slightly unexpected,
09:12
and the very most interesting,
09:13
let me put it that way, contact that I had,
09:16
was actually from a team of American footballers
09:19
that all wanted to have double-thickness skulls
09:22
made on their head.
09:25
And so you do get these kinds of contacts,
09:30
and of course, being British
09:32
and also growing up in France,
09:35
I tend to be very blunt,
09:37
and so I had to explain to them very nicely
09:39
that in their particular case,
09:41
there probably wasn't that much in there
09:42
to protect in the first place.
09:44
(Laughter)
09:47
(Applause)
09:49
So this was our approach,
09:50
and it was simple materials,
09:52
but we thought about it carefully.
09:54
And actually we know that those cells
09:56
in the body, in the embryo, as they develop
09:57
can form a different kind of tissue, cartilage,
09:59
and so we developed a gel that was slightly different
10:03
in nature and slightly different chemistry,
10:05
put it in there, and we were able to get
10:08
100 percent cartilage instead.
10:10
And this approach works really well, I think,
10:12
for pre-planned procedures,
10:14
but it's something you do have to pre-plan.
10:16
So for other kinds of operations,
10:19
there's definitely a need for other
10:22
scaffold-based approaches.
10:23
And when you think about designing
10:26
those other scaffolds, actually,
10:28
you need a really multi-disciplinary team.
10:30
And so our team has chemists,
10:32
it has cell biologists, surgeons, physicists even,
10:34
and those people all come together
10:37
and we think really hard about
designing the materials.
10:39
But we want to make them have enough information
10:42
that we can get the cells to do what we want,
10:45
but not be so complex as to make it difficult
10:47
to get to clinic.
10:49
And so one of the things we think about a lot
10:51
is really trying to understand
10:54
the structure of the tissues in the body.
10:55
And so if we think of bone,
10:58
obviously my own favorite tissue,
11:00
we zoom in, we can see,
11:02
even if you don't know anything
about bone structure,
11:04
it's beautifully organized,
really beautifully organized.
11:06
We've lots of blood vessels in there.
11:08
And if we zoom in again, we see that the cells
11:10
are actually surrounded by a 3D matrix
11:12
of nano-scale fibers, and they give a lot
11:15
of information to the cells.
11:17
And if we zoom in again,
11:20
actually in the case of bone, the matrix
11:21
around the cells is beautifully organized
11:23
at the nano scale, and it's a hybrid material
11:26
that's part organic, part inorganic.
11:28
And that's led to a whole field, really,
11:31
that has looked at developing materials
11:33
that have this hybrid kind of structure.
11:35
And so I'm showing here just two examples
11:38
where we've made some materials
that have that sort of structure,
11:41
and you can really tailor it.
11:44
You can see here a very squishy one
11:46
and now a material that's also
this hybrid sort of material
11:48
but actually has remarkable toughness,
11:52
and it's no longer brittle.
11:54
And an inorganic material
would normally be really brittle,
11:55
and you wouldn't be able to have
11:58
that sort of strength and toughness in it.
11:59
One other thing I want to quickly mention is that
12:01
many of the scaffolds we make
are porous, and they have to be,
12:04
because you want blood vessels to grow in there.
12:07
But the pores are actually oftentimes
12:09
much bigger than the cells,
12:11
and so even though it's 3D,
12:12
the cell might see it more
as a slightly curved surface,
12:14
and that's a little bit unnatural.
12:17
And so one of the things you can think about doing
12:19
is actually making scaffolds
with slightly different dimensions
12:21
that might be able to surround your cells in 3D
12:24
and give them a little bit more information.
12:27
And there's a lot of work going
on in both of these areas.
12:29
Now finally, I just want to talk a little bit about
12:33
applying this sort of thing to cardiovascular disease,
12:37
because this is a really big clinical problem.
12:40
And one of the things that we know is that,
12:43
unfortunately, if you have a heart attack,
12:46
then that tissue can start to die,
12:49
and your outcome may not be very good over time.
12:52
And it would be really great, actually,
12:55
if we could stop that dead tissue
12:57
either from dying or help it to regenerate.
12:59
And there's lots and lots of stem
cell trials going on worldwide,
13:03
and they use many different types of cells,
13:06
but one common theme that seems to be coming out
13:08
is that actually, very often, those cells will die
13:11
once you've implanted them.
13:14
And you can either put them into the heart
13:15
or into the blood system,
13:17
but either way, we don't seem to be able
13:19
to get quite the right number of cells
13:22
getting to the location we want them to
13:24
and being able to deliver the sort of beautiful
13:26
cell regeneration that we would like to have
13:30
to get good clinical outcomes.
13:33
And so some of the things that we're thinking of,
13:36
and many other people in the field are thinking of,
13:38
are actually developing materials for that.
13:42
But there's a difference here.
13:45
We still need chemistry, we still need mechanics,
13:46
we still need really interesting topography,
13:48
and we still need really interesting
ways to surround the cells.
13:51
But now, the cells also
13:54
would probably quite like a material
13:56
that's going to be able to be conductive,
13:58
because the cells themselves will respond very well
14:00
and will actually conduct signals
between themselves.
14:05
You can see them now
14:08
beating synchronously on these materials,
14:10
and that's a very, very exciting development
14:12
that's going on.
14:15
So just to wrap up, I'd like to actually say that
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being able to work in this sort of field,
14:22
all of us that work in this field
14:24
that's not only super-exciting science,
14:26
but also has the potential
14:28
to impact on patients,
14:30
however big or small they are,
14:32
is really a great privilege.
14:35
And so for that, I'd like to thank all of you as well.
14:36
Thank you.
14:39
(Applause)
14:41

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About the Speaker:

Molly Stevens - Biomaterials researcher
Molly Stevens studies and creates new biomaterials that could be used to detect disease and repair bones and human tissue.

Why you should listen

At Imperial College London, Molly Stevens heads a highly multidisciplinary research group that designs bioactive materials for regenerative medicine and biosensing. It's fundamental science with an eye to practical applications as healthcare products.

Among the products from her lab: an engineered bone, cardiac tissue suitable for use in transplants, and disease-sensing nanoparticle aggregates that change color in the presence of even tiny quantities of cancer-related enzymes, making early sensing possible. As Stevens told The Lancet: "It's right down at the nanoscience level. It's really exciting stuff, but it actually results in something very tangibly useful."

More profile about the speaker
Molly Stevens | Speaker | TED.com