Molly Stevens: A new way to grow bone

翻译人员: Li Li 校对人员: Rong Han

As humans, it's in our nature

作为人类，我们本能地希望

to want to improve our health and minimize our suffering.

使自己更健康，少受痛楚。

Whatever life throws at us,

无论我们在生活中遭遇到什么，

whether it's cancer, diabetes, heart disease,

不管是癌症，糖尿病，心脏病，

or even broken bones, we want to try and get better.

或是骨折，我们都想尽快康复。

Now I'm head of a biomaterials lab,

我是一间生物材料实验室的负责人，

and I'm really fascinated by the way that humans

而且我对历史上人类

have used materials in really creative ways

别出心裁地将不同的材料

in the body over time.

使用在人体上十分感兴趣。

Take, for example, this beautiful blue nacre shell.

举个例子，这个漂亮的蓝色珍珠贝壳，

This was actually used by the Mayans

它其实是被玛雅人

as an artificial tooth replacement.

当作人造牙齿来使用的。

We're not quite sure why they did it.

我们还不是很确定他们为什么要这么做。

It's hard. It's durable.

这东西坚硬，耐用，

But it also had other very nice properties.

但它也具备其他优秀的特征。

In fact, when they put it into the jawbone,

实际上 ，当他们把它放进颚骨时，

it could integrate into the jaw,

它可以和颚骨结合在一起。

and we know now with very sophisticated

现在，在精密的成像技术的帮助下

imaging technologies

我们明白了，

that part of that integration comes from the fact

之所以能结合，部分原因是因为

that this material is designed

这种材料的设计

in a very specific way, has a beautiful chemistry,

有非常独特的地方，它有良好的化学性质，

has a beautiful architecture.

和良好的构造。

And I think in many ways we can sort of think

而且我觉得，在很多方面，

of the use of the blue nacre shell and the Mayans

我们可以把蓝色珍珠贝壳和玛雅人这个例子，

as the first real application

当作蓝牙技术的

of the bluetooth technology.

首个真正应用。

(Laughter)

（笑声）

But if we move on and think throughout history

如果我们沿着时间的发展来思考整个历史进程中

how people have used different materials in the body,

人类是如何在人体上运用不同材料的，

very often it's been physicians

我们会发现，频频出现的

that have been quite creative.

是那些极具创意的医生，

They've taken things off the shelf.

他们都是就地取材。

One of my favorite examples

我最喜欢的一个例子，

is that of Sir Harold Ridley,

是关于哈罗德•里德利爵士的。

who was a famous ophthalmologist,

他是一位著名的眼科医生，

or at least became a famous ophthalmologist.

至少是成为了著名的眼科医生。

And during World War II, what he would see

在二战期间，他注意到

would be pilots coming back from their missions,

执行完任务回来的飞行员的眼睛里，

and he noticed that within their eyes

执行完任务回来的飞行员的眼睛里，

they had shards of small bits of material

有一些细小的碎片藏在里面，

lodged within the eye,

有一些细小的碎片藏在里面，

but the very interesting thing about it

但比较有趣的是，

was that material, actually, wasn't causing

这些碎片材料

any inflammatory response.

并没有引发任何炎症。

So he looked into this, and he figured out

经过调查他发现，

that actually that material was little shards of plastic

这是一些塑料碎片，

that were coming from the canopy of the Spitfires.

是喷火式战斗机座舱罩的一部分。

And this led him to propose that material

由此他提出把这种材料

as a new material for intraocular lenses.

当作人工晶体的新材料。

It's called PMMA, and it's now used

它叫做PMMA（聚甲基丙烯酸甲酯），

in millions of people every year

如今它每年都造福数百万人民，

and helps in preventing cataracts.

帮助预防白内障。

And that example, I think, is a really nice one,

我觉得这是一个很好的例子，

because it helps remind us that in the early days,

因为它提醒我们，

people often chose materials

在过去人们之所以选择某种材料

because they were bioinert.

是因为它是生物惰性材料，

Their very purpose was to perform a mechanical function.

他们只是想发挥它的机械性能。

You'd put them in the body

你把它植入体内，

and you wouldn't get an adverse response.

不会有不良反应。

And what I want to show you is that

我要给你们看的是，

in regenerative medicine,

在再生医学领域，

we've really shifted away from that idea

我们的观念已经发生改变，

of taking a bioinert material.

不再从生物惰性材料上取材，

We're actually actively looking for materials

我们现在在积极寻找新的材料，

that will be bioactive, that will interact with the body,

能和人体相互作用的生物活性材料，

and that furthermore we can put in the body,

并且我们能将之植入体内，

they'll have their function,

它们发挥作用之后，

and then they'll dissolve away over time.

随着时间的推移它们会自动溶解。

If we look at this schematic,

我们看下这个示意图，

this is showing you what we think of

它给我们展示了

as the typical tissue-engineering approach.

典型的组织工程学方法。

We have cells there, typically from the patient.

我们从病人身上提取细胞，

We can put those onto a material,

把它们放在某种材料上，

and we can make that material very complex if we want to,

如果需要，我们还可以把材料弄得复杂一点，

and we can then grow that up in the lab

然后我们就能在实验室里进行培养，

or we can put it straight back into the patient.

或者就直接放回病人身体内。

And this is an approach that's used all over the world,

这种方法在全世界普遍使用，

including in our lab.

包括我们实验室。

But one of the things that's really important

我们在想到干细胞的时候，

when we're thinking about stem cells

有非常重要的一点，

is that obviously stem cells can be many different things,

就是干细胞显然可以变成很多不同的东西，

and they want to be many different things,

并且也希望它们能长成不同的东西，

and so we want to make sure that the environment

所以我们要确保放干细胞的环境中

we put them into has enough information

有足够多的信息，

so that they can become the right sort

这样它们才能发育成我们想要的

of specialist tissue.

那种特定的组织。

And if we think about the different types of tissues

如果我们想想那些

that people are looking at regenerating

在全世界不同的实验室里，

all over the world, in all the different labs in the world,

人们正试图再生的各种不同类型的组织，

there's pretty much every tissue you can think of.

基本就包括了差不多你能想到的所有组织。

And actually, the structure of those tissues

事实上，那些组织的结构

is quite different, and it's going to really depend

都挺不同的，要怎样去再造组织，

on whether your patient has any underlying disease,

绝大部分要取决于，

other conditions, in terms of how

你的病人是否有一些潜在疾病，

you're going to regenerate your tissue,

以及一些其他的条件。

and you're going to need to think about the materials

你还需要非常认真地考虑

you're going to use really carefully,

要使用什么材料，

their biochemistry, their mechanics,

考虑它们的生化特征，它们的结构，

and many other properties as well.

和其他的一些特性。

Our tissues all have very different abilities to regenerate,

我们身体里的组织都具有非常不同的再生能力。

and here we see poor Prometheus,

我们来看看可怜的普罗米修斯 （希腊神话中人名，为人类盗火种甘受罚），

who made a rather tricky career choice

他做了一个比较苦逼的职业抉择，

and was punished by the Greek gods.

然后就被希腊的神给惩罚了。

He was tied to a rock, and an eagle would come

他被绑到一块石头上，然后每天都会有一只老鹰

every day to eat his liver.

飞过来啄食他的肝。

But of course his liver would regenerate every day,

当然，他的肝每天都会再生，

and so day after day he was punished

所以他就这样日复一日，年复一年，

for eternity by the gods.

永远不停地接受神的惩罚。

And liver will regenerate in this very nice way,

肝会这样完美地再生，

but actually if we think of other tissues,

但如果我们想一下别的组织，

like cartilage, for example,

比如像软骨，

even the simplest nick and you're going to find it

哪怕是最简单的小切口，

really difficult to regenerate your cartilage.

软骨都很难再生出来。

So it's going to be very different from tissue to tissue.

所以，再生能力是因组织而异的，

Now, bone is somewhere in between,

骨头呢，介于两者之间。

and this is one of the tissues that we work on a lot in our lab.

我们实验室在骨头上做了大量的工作。

And bone is actually quite good at repairing.

骨头的修复能力其实相当不错，

It has to be. We've probably all had fractures

它必须得是这样的。

at some point or other.

我们可能都有过骨折的经历吧。

And one of the ways that you can think

而要想修复骨折，

about repairing your fracture

一个方法

is this procedure here, called an iliac crest harvest.

就叫髂骨移植法。

And what the surgeon might do

外科医生可能

is take some bone from your iliac crest,

会从你的髂骨那取些骨头，

which is just here,

就在这儿，

and then transplant that somewhere else in the body.

然后移植到身体的别的部位。

And it actually works really well,

这个方法其实很有效，

because it's your own bone,

因为它是你自己身上的骨头，

and it's well vascularized,

而且有充分的血管浸润，

which means it's got a really good blood supply.

也就是说供血良好。

But the problem is, there's only so much you can take,

但问题就是，你能用得就只有那么多，

and also when you do that operation,

而且当你在进行这项手术时，

your patients might actually have significant pain

你的病人可能会在缺位那里产生极大的疼痛，

in that defect site even two years after the operation.

哪怕手术两年后还会感到疼痛。

So what we were thinking is,

所以我们想的是，

there's a tremendous need for bone repair, of course,

骨头修复肯定有大量的需求，

but this iliac crest-type approach

但这种髂骨方法

really has a lot of limitations to it,

有太多的局限性，

and could we perhaps recreate

那么我们是否能

the generation of bone within the body

在体内重新制造出所需的骨头，

on demand and then be able to transplant it

然后将之进行移植，

without these very, very painful aftereffects

而又不像髂骨方法那样

that you would have with the iliac crest harvest?

产生痛苦的后果？

And so this is what we did, and the way we did it

我们是这样做的，

was by coming back to this typical tissue-engineering approach

我们的方法就是回到组织工程学，

but actually thinking about it rather differently.

但是要用不同的思维方式。

And we simplified it a lot,

而且我们将之大大简化，

so we got rid of a lot of these steps.

我们去掉了很多步骤，

We got rid of the need to harvest cells from the patient,

我们减掉了从病人身上提取细胞这一步骤，

we got rid of the need to put in really fancy chemistries,

我们减掉了使用华丽的化学反应的必要性，

and we got rid of the need

我们还去掉了

to culture these scaffolds in the lab.

在实验室里搭建这些支架的必要性。

And what we really focused on

所以我们真正关注的

was our material system and making it quite simple,

是我们的材料系统，并尽量简化，

but because we used it in a really clever way,

但因为我们用了巧妙的方法，

we were able to generate enormous amounts of bone

所以我们就能非常大量地生产骨骼。

using this approach.

所以我们就能非常大量地生产骨骼。

So we were using the body

所以我们是利用身体，

as really the catalyst to help us

把它当作催化剂来使用，

to make lots of new bone.

以此产生新骨骼。

And it's an approach that we call

这就是我们所称的

the in vivo bioreactor, and we were able to make

体内生物反应器，

enormous amounts of bone using this approach.

我们可以用这种方法大量制造骨骼。

And I'll talk you through this.

我详细跟你们讲下。

So what we do is,

所以我们所做的就是，

in humans, we all have a layer of stem cells

在体内我们的长骨外面，

on the outside of our long bones.

都有一层干细胞，

That layer is called the periosteum.

这一层叫做骨膜。

And that layer is actually normally

这层骨膜通常来说

very, very tightly bound to the underlying bone,

和在它下面的骨骼是紧密相连的，

and it's got stem cells in it.

而且里面含有干细胞，

Those stem cells are really important

这些干细胞在胚胎发育时期

in the embryo when it develops,

有着非常重要的作用，

and they also sort of wake up if you have a fracture

而且当你不慎骨折的时候，

to help you with repairing the bone.

它们会被激活以修复骨骼。

So we take that periosteum layer

所以我们要利用骨膜层，

and we developed a way to inject underneath it

我们想办法在它下面注入一种液体，

a liquid that then, within 30 seconds,

然后在30秒内

would turn into quite a rigid gel

会变成一种硬胶。

and can actually lift the periosteum away from the bone.

这样就将骨膜提起，与骨骼分离，

So it creates, in essence, an artificial cavity

所以本质上它制造了一个人造空腔，

that is right next to both the bone

就在骨骼

but also this really rich layer of stem cells.

和干细胞层中间。

And we go in through a pinhole incision

我们通过一个针孔切口进入，

so that no other cells from the body can get in,

这样身上别的细胞就进不去，

and what happens is that that artificial in vivo bioreactor cavity

这个人造的体内生物反应腔

can then lead to the proliferation of these stem cells,

能促进这些干细胞的增殖，

and they can form lots of new tissue,

而它们就能形成许多新的组织。

and then over time, you can harvest that tissue

过一段时间后，就可以收取这些组织，

and use it elsewhere in the body.

并用到身上其他地方去。

This is a histology slide

这张组织学切片显示了

of what we see when we do that,

我们采用这种方法之后所看到的样子。

and essentially what we see

我们主要看到的

is very large amounts of bone.

是大量的骨骼，

So in this picture, you can see the middle of the leg,

在这张图中，你们可以看到腿中间的部位，

so the bone marrow,

也就是骨髓，

then you can see the original bone,

还可以看到原来的骨骼，

and you can see where that original bone finishes,

以及原来的骨骼结束的位置，

and just to the left of that is the new bone

在左边的就是新生的骨骼，

that's grown within that bioreactor cavity,

就是在生物反应腔生长的，

and you can actually make it even larger.

事实上你还可以让它生长得更大。

And that demarcation that you can see

另外你们所看到的，

between the original bone and the new bone

在原骨骼和新骨骼之间的分界线，

acts as a very slight point of weakness,

算是比较薄弱的地方，

so actually now the surgeon can come along,

所以现在外科医生就可以来

can harvest away that new bone,

把新骨骼取走，

and the periosteum can grow back,

而骨膜能长回来，

so you're left with the leg

所以你的腿

in the same sort of state

也会恢复原貌，

as if you hadn't operated on it in the first place.

就像什么都没发生过一样。

So it's very, very low in terms of after-pain

所以相比髂骨移植法，

compared to an iliac crest harvest.

这种方法大大减少了术后疼痛，

And you can grow different amounts of bone

而且你注入多少胶进去，

depending on how much gel you put in there,

就能生长出多少骨骼来，

so it really is an on demand sort of procedure.

所以这种方法算是一种按需供应的方法。

Now, at the time that we did this,

当我们在做这个项目的时候，

this received a lot of attention in the press,

媒体给予我们很多的关注，

because it was a really nice way

因为这是一种十分理想的

of generating new bone,

产生新骨骼的方法。

and we got many, many contacts

也有很多很多不同的人和我们联系，

from different people that were interested in using this.

对使用这种方法十分感兴趣。

And I'm just going to tell you,

我在这里跟你们说吧

sometimes those contacts are very strange,

有时这些和我们联系的人很奇怪，

slightly unexpected,

有点出乎意料，

and the very most interesting,

最有趣的，

let me put it that way, contact that I had,

我这么说吧，和我联系的人，

was actually from a team of American footballers

是一个来自美国的橄榄球队，

that all wanted to have double-thickness skulls

他们希望他们的脑袋里

made on their head.

头盖骨能长到双倍的厚度。

And so you do get these kinds of contacts,

所以是会有这样的人和你联系的。

and of course, being British

当然作为一个英国人，

and also growing up in France,

又自小在法国长大，

I tend to be very blunt,

我是比较坦率的，

and so I had to explain to them very nicely

我不得不委婉地解释说，

that in their particular case,

像他们这种情况，

there probably wasn't that much in there

那里本身大概

to protect in the first place.

也没多少可保护的。

(Laughter)

（笑声）

(Applause)

（掌声）

So this was our approach,

所以这就是我们的方法。

and it was simple materials,

材料很简单，

but we thought about it carefully.

但我们是经过精心思考的。

And actually we know that those cells

而且我们也知道体内的这些细胞，

in the body, in the embryo, as they develop

在胚胎时期，当他们生长的时候，

can form a different kind of tissue, cartilage,

还能形成另一种不同的组织，就是软骨，

and so we developed a gel that was slightly different

所以我们又制造了一种性质和原先不大一样的胶体，

in nature and slightly different chemistry,

化学效应也稍有不同，

put it in there, and we were able to get

把它们注入，

100 percent cartilage instead.

我们就能得到百分之百的软骨。

And this approach works really well, I think,

我觉得这个方法

for pre-planned procedures,

对于预先计划好的手术来说效果是很不错的，

but it's something you do have to pre-plan.

但你必须得预先计划好。

So for other kinds of operations,

所以对其他类型的手术来说，

there's definitely a need for other

采用支架方法

scaffold-based approaches.

是非常有必要的。

And when you think about designing

当你在思考

those other scaffolds, actually,

设计那些支架的时候，

you need a really multi-disciplinary team.

你需要一个多学科的团队。

And so our team has chemists,

所以我们的团队里有化学家，

it has cell biologists, surgeons, physicists even,

还有细胞生物学家，外科医生，甚至还有物理学家，

and those people all come together

这些人都走到了一起，

and we think really hard about designing the materials.

而且我们竭尽心思设计那些材料。

But we want to make them have enough information

我们希望它们能提供足够多的信息，

that we can get the cells to do what we want,

让我们能使细胞按我们的要求行动，

but not be so complex as to make it difficult

但又不能太复杂，

to get to clinic.

以免在临床上难以实践。

And so one of the things we think about a lot

所以我们经常思考的事项之一，

is really trying to understand

就是试图去明白

the structure of the tissues in the body.

人体内组织的结构。

And so if we think of bone,

当我们一想到骨骼时，

obviously my own favorite tissue,

显然这是我最喜欢的组织，

we zoom in, we can see,

我们把它放大，就能看到，

even if you don't know anything about bone structure,

就算你一点都不知道骨骼结构也能看到，

it's beautifully organized, really beautifully organized.

它结构很优美，真的很美，

We've lots of blood vessels in there.

那里还有很多血管。

And if we zoom in again, we see that the cells

我们再放大，就能看到

are actually surrounded by a 3D matrix

这些细胞被纳米级别的纤维

of nano-scale fibers, and they give a lot

像3D矩阵一样环绕着，

of information to the cells.

他们为细胞提供很多信息。

And if we zoom in again,

如果我们再放大，

actually in the case of bone, the matrix

对骨骼来说，

around the cells is beautifully organized

细胞周围的基质也形成纳米大小的优美结构。

at the nano scale, and it's a hybrid material

而且它还是一种杂合性的材料，

that's part organic, part inorganic.

就是部分有机，部分无机。

And that's led to a whole field, really,

这为我们开拓了一个新的领域，真的，

that has looked at developing materials

就是试图开发出

that have this hybrid kind of structure.

具有这种杂合性结构的材料。

And so I'm showing here just two examples

我在这里给大家看两个例子，

where we've made some materials that have that sort of structure,

就是我们制造的有这种结构的物质，

and you can really tailor it.

而且是可以量身定做的。

You can see here a very squishy one

这边你可以看到软软的这一种，

and now a material that's also this hybrid sort of material

而这边是一种杂合性材料做成的，

but actually has remarkable toughness,

它的坚韧性非常显著，

and it's no longer brittle.

而且它一点也不脆。

And an inorganic material would normally be really brittle,

无机材料通常都比较脆，

and you wouldn't be able to have

你就没有办法

that sort of strength and toughness in it.

得到这种强度和韧性的。

One other thing I want to quickly mention is that

另外一个我想很快地提一下，

many of the scaffolds we make are porous, and they have to be,

就是我们做的很多支架都是多孔的，这是必须的，

because you want blood vessels to grow in there.

因为你得让血管在里面发育生长。

But the pores are actually oftentimes

但是这些孔很多时候

much bigger than the cells,

却比细胞要大得多，

and so even though it's 3D,

所以即使它是3D的，

the cell might see it more as a slightly curved surface,

对于细胞来说可能会是一个弯曲的表面，

and that's a little bit unnatural.

而这是有点违背自然规律的。

And so one of the things you can think about doing

所以我们能做的

is actually making scaffolds with slightly different dimensions

就是做一些稍微不同维度的支架，

that might be able to surround your cells in 3D

这样就能3D地包围细胞，

and give them a little bit more information.

让他们能拥有多一点信息。

And there's a lot of work going on in both of these areas.

在这两个领域里，都有很多工作在进行着。

Now finally, I just want to talk a little bit about

最后，我还想说说

applying this sort of thing to cardiovascular disease,

在心血管疾病方面运用这种技术。

because this is a really big clinical problem.

因为这是临床上一个比较大的问题。

And one of the things that we know is that,

而我们所知的一件事就是，

unfortunately, if you have a heart attack,

如果你不幸心脏病突发，

then that tissue can start to die,

那么那里的组织会开始死亡，

and your outcome may not be very good over time.

时间拖得越久，后果可能越严重。

And it would be really great, actually,

如果我们能够，

if we could stop that dead tissue

让死亡的组织不再继续死下去，

either from dying or help it to regenerate.

或使它再生，那将很了不起。

And there's lots and lots of stem cell trials going on worldwide,

现在在全世界范围内有很多这样的干细胞实验，

and they use many different types of cells,

他们使用很多不同种类的细胞，

but one common theme that seems to be coming out

但似乎得到的都是同一个结果，

is that actually, very often, those cells will die

就是这些细胞，一旦你将之移植

once you've implanted them.

通常都会死掉。

And you can either put them into the heart

你可以把他们移植到心脏

or into the blood system,

或血液中，

but either way, we don't seem to be able

但不管哪一种方式，我们似乎都没法

to get quite the right number of cells

使足够数量的细胞

getting to the location we want them to

到我们想要的地方去，

and being able to deliver the sort of beautiful

然后进行细胞再生，

cell regeneration that we would like to have

那样我们才能

to get good clinical outcomes.

得到较好的临床效果。

And so some of the things that we're thinking of,

所以我们在思考的一些问题，

and many other people in the field are thinking of,

而且很多同行的人也在思考的一些问题，

are actually developing materials for that.

就是为此制造材料。

But there's a difference here.

但这里有不同之处，

We still need chemistry, we still need mechanics,

我们仍须化学和机械学，

we still need really interesting topography,

我们还需要有趣的拓扑学，

and we still need really interesting ways to surround the cells.

我们也需要有新意的方式来环绕细胞。

But now, the cells also

但是这些细胞

would probably quite like a material

可能也很像

that's going to be able to be conductive,

一种具有传导性的材料，

because the cells themselves will respond very well

因为细胞自身会很好地反馈

and will actually conduct signals between themselves.

而且在彼此之间传导信息。

You can see them now

你在这能看到

beating synchronously on these materials,

细胞在这些材料上同步地跳动着，

and that's a very, very exciting development

这是非常非常振奋人心的进展。

that's going on.

这是非常非常振奋人心的进展。

So just to wrap up, I'd like to actually say that

总结一下，我想说，

being able to work in this sort of field,

能够在这样的领域工作，

all of us that work in this field

对于我们所有在这个领域工作的人而言，

that's not only super-exciting science,

这不仅是超级让人兴奋的科学，

but also has the potential

它还有潜力

to impact on patients,

对病人产生影响，

however big or small they are,

不论这影响是大是小，

is really a great privilege.

对我们都是一种荣幸。

And so for that, I'd like to thank all of you as well.

为此我也要对你们说声感谢。

Thank you.

谢谢你们。

(Applause)

（掌声）