Molly Stevens: A new way to grow bone

譯者: NAN-KUN WU 審譯者: Ying Wang

As humans, it's in our nature

身為人，想要增進健康以及

to want to improve our health and minimize our suffering.

減少痛苦是我們的天性。

Whatever life throws at us,

不論我們在生命中得到了什麼，

whether it's cancer, diabetes, heart disease,

不管是癌症、糖尿病、心臟病，

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

或甚至是骨折，我們都想要試著好起來。

Now I'm head of a biomaterials lab,

我現在是一間 生物材料實驗室的主持人，

and I'm really fascinated by the way that humans

我對於人類自古以來，

have used materials in really creative ways

在體內所使用的材料方面的創意

in the body over time.

感到相當驚訝。

Take, for example, this beautiful blue nacre shell.

例如這個珍珠貝漂亮的殼，

This was actually used by the Mayans

它曾經被馬雅人

as an artificial tooth replacement.

用來當做人工的牙齒替代品。

We're not quite sure why they did it.

我們並不清楚他們為什麼這麼做，

It's hard. It's durable.

它很硬，也很耐用，

But it also had other very nice properties.

但是它也有其它很棒的特性。

In fact, when they put it into the jawbone,

事實上，當它們被放到頜骨裡面，

it could integrate into the jaw,

可能會和骨頭合而為一。

and we know now with very sophisticated

先進的影像技術顯示，

imaging technologies

兩者相融的一部分原因

that part of that integration comes from the fact

來自於這種材料的

that this material is designed

特殊之處。

in a very specific way, has a beautiful chemistry,

不論在結構上

has a beautiful architecture.

或是化學上都是如此。

And I think in many ways we can sort of think

我認為在某些程度上，

of the use of the blue nacre shell and the Mayans

用了藍珍珠貝的馬雅人

as the first real application

是藍牙技術的

of the bluetooth technology.

先驅。

(Laughter)

（笑聲）

But if we move on and think throughout history

如果我們觀察歷史上

how people have used different materials in the body,

人類是如何將不同的材料運用在身體上，

very often it's been physicians

就會發現這些傑作常常

that have been quite creative.

來自富有創意的醫師。

They've taken things off the shelf.

他們時常創新。

One of my favorite examples

我最喜歡的一個例子

is that of Sir Harold Ridley,

是關於 Harold Ridley 爵士。

who was a famous ophthalmologist,

他是一位有名的眼科醫師，

or at least became a famous ophthalmologist.

或至少成為了一位有名的眼科醫師。

And during World War II, what he would see

二次大戰期間，

would be pilots coming back from their missions,

他見到從任務結束后歸來的飛行員。

and he noticed that within their eyes

他注意到這些飛行員的眼睛裡

they had shards of small bits of material

卡了碎片，或是

lodged within the eye,

其它的小東西。

but the very interesting thing about it

但是有趣的是

was that material, actually, wasn't causing

這些東西並沒有

any inflammatory response.

引起任何的發炎反應。

So he looked into this, and he figured out

因此他仔細的調查了這件事，

that actually that material was little shards of plastic

他發現這些塑膠碎片

that were coming from the canopy of the Spitfires.

其實是來自噴火式戰機的座艙蓋。

And this led him to propose that material

這讓他提出使用這種物質

as a new material for intraocular lenses.

來製作新型人工水晶體。

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

這種物質叫做 PMMA，它現在每年

in millions of people every year

幫助數百萬人

and helps in preventing cataracts.

免於罹患白內障。

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

我認為這個例子非常非常棒，

because it helps remind us that in the early days,

因為它提醒了我們，

people often chose materials

從前的人們總是根據生物惰性

because they were bioinert.

來選擇材料，

Their very purpose was to perform a mechanical function.

它們的唯一目的 就是進行機械的功能；

You'd put them in the body

你會把它們放進身體裡，

and you wouldn't get an adverse response.

而且不希望身體產生不良反應。

And what I want to show you is that

我想要展示給你們看的是

in regenerative medicine,

在再生醫學中，

we've really shifted away from that idea

我們並非一如往常地

of taking a bioinert material.

選擇生物惰性材料。

We're actually actively looking for materials

事實上我們積極地尋找

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

會和身體產生反應的生物活性材料，

and that furthermore we can put in the body,

而且當我們把它們放到身體裡。

they'll have their function,

它們會執行功能，

and then they'll dissolve away over time.

然後會隨著時間被分解掉，

If we look at this schematic,

當我們仔細思考這個概念，

this is showing you what we think of

這是在告訴你們，

as the typical tissue-engineering approach.

我們心目中典型的生物工程技術。

We have cells there, typically from the patient.

我們有些細胞基本上是來自病人，

We can put those onto a material,

我們能夠把這些細胞放到材料上，

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

如果想要的話，我們也 可以把這些材料做得很複雜，

and we can then grow that up in the lab

然後我們在實驗室裡培養這些細胞，

or we can put it straight back into the patient.

或者直接放回病患體內。

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

這項技術在全世界被使用，

including in our lab.

包括我們的實驗室。

But one of the things that's really important

但是最重要的一件事情是：

when we're thinking about stem cells

當我們講到幹細胞時，

is that obviously stem cells can be many different things,

顯然它們能夠做到很多事，

and they want to be many different things,

它們也想做很多事，

and so we want to make sure that the environment

所以要確保我們讓它們生長的環境

we put them into has enough information

擁有足夠的訊息。

so that they can become the right sort

使幹細胞特化成為

of specialist tissue.

正確的組織。

And if we think about the different types of tissues

人們在世界各地的實驗室裡尋找

that people are looking at regenerating

各式各樣

擁有再生能力的組織，

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

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

你所能想的到的各種組織都有，

And actually, the structure of those tissues

而且事實上這些組織之間

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

有很大的差異，

on whether your patient has any underlying disease,

也基於病人是否擁有相關疾病，

other conditions, in terms of how

或是其它的條件來決定。

you're going to regenerate your tissue,

要如何讓組織再生，

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

也要謹慎選擇材料

you're going to use really carefully,

和使用材料；

their biochemistry, their mechanics,

要考慮到這些材料的生化、機械

and many other properties as well.

以及其它的特性。

Our tissues all have very different abilities to regenerate,

我們所有的組織再生的能力迥異，

and here we see poor Prometheus,

就像是可憐的普羅米修斯，

who made a rather tricky career choice

因為他一個狡猾的生涯決定

and was punished by the Greek gods.

而被希臘諸神所懲罰。

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

他被綁在一塊石頭上，每天都會有一隻老鷹

every day to eat his liver.

來啄食他的肝臟。

But of course his liver would regenerate every day,

當然他的肝臟每天都會長回來，

and so day after day he was punished

所以諸神的懲罰日復一日

for eternity by the gods.

直到永遠。

And liver will regenerate in this very nice way,

肝臟有很強的再生能力，

but actually if we think of other tissues,

但是其它的組織就不一樣了，

like cartilage, for example,

以軟骨來說，

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

即使是一個小缺損

really difficult to regenerate your cartilage.

也很難長回來。

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

所以組織之間有很大的差異。

Now, bone is somewhere in between,

好，骨骼介於兩者之間，

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

也是我們實驗室努力研究的對象。

And bone is actually quite good at repairing.

其實骨骼也很善於修補。

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

它必須如此。我們可能

at some point or other.

都曾經經歷過骨折，

And one of the ways that you can think

有一種你可能想像得到的

修補骨折的方法，

about repairing your fracture

is this procedure here, called an iliac crest harvest.

叫做髂嵴修補法。

And what the surgeon might do

外科醫師會做的

is take some bone from your iliac crest,

是取出髂嵴的部分骨骼，

which is just here,

就像這樣，

and then transplant that somewhere else in the body.

然後移植到身體的其它部位。

And it actually works really well,

這真的相當有效，

because it's your own bone,

因為它是你自己的骨頭，

and it's well vascularized,

同時也具有完整的血管系統，

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

也就是說它能得到充足的血液供應。

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

但是問題在於 你能取出的骨骼很有限，

and also when you do that operation,

而且在你進行手術之後兩年內，

your patients might actually have significant pain

手術部位可能

in that defect site even two years after the operation.

會讓病人感到相當痛苦。

So what we were thinking is,

所以我們在思考的是，

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

當然，骨骼的修復是很重要的，

but this iliac crest-type approach

但是這種髂嵴修補法

really has a lot of limitations to it,

有很多限制，

and could we perhaps recreate

我們能夠想出一種方法

the generation of bone within the body

讓骨頭在身體裡面再生

on demand and then be able to transplant it

並且能夠移植它

without these very, very painful aftereffects

同時避免像是髂嵴修補法產生的

that you would have with the iliac crest harvest?

劇烈疼痛等後遺症嗎？

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

我們做到了，我們用的方法又回到 典型的組織工程法

was by coming back to this typical tissue-engineering approach

我們做到了，我們用的方法 又回到典型的組織工程法，

but actually thinking about it rather differently.

但是卻有不同的思路。

And we simplified it a lot,

我們也把它簡化了很多，

so we got rid of a lot of these steps.

所以可以省略很多步驟。

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

我們省略了從病人體內取出細胞的步驟，

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

省略了把細胞放進 令人眼花繚亂的化學物質

and we got rid of the need

也省略了

to culture these scaffolds in the lab.

在實驗室裡培養這些組織的架構。

And what we really focused on

我們著重在於

was our material system and making it quite simple,

簡化材料系統，

but because we used it in a really clever way,

這樣的巧思，

we were able to generate enormous amounts of bone

讓我們能夠通過這種方法

using this approach.

作出大量的骨骼。

So we were using the body

我們把身體

as really the catalyst to help us

當做催化劑，

to make lots of new bone.

幫我們做出很多的新骨骼。

And it's an approach that we call

我們把這樣的方法

the in vivo bioreactor, and we were able to make

叫做體內生物反應器，利用這樣的方法

enormous amounts of bone using this approach.

我們能作出大量的骨骼。

And I'll talk you through this.

我現在詳細說明給你們聽。

So what we do is,

我們是這樣做的，

in humans, we all have a layer of stem cells

在人類的長骨外面

on the outside of our long bones.

有一層幹細胞。

That layer is called the periosteum.

叫做骨膜。

And that layer is actually normally

這層細胞通常會 非常非常緊密的和

very, very tightly bound to the underlying bone,

下面的骨頭結合，

and it's got stem cells in it.

幹細胞就位在其中

Those stem cells are really important

這些幹細胞

in the embryo when it develops,

對胚胎發育很重要，

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

而它們在你骨折的時候就像被喚醒了一樣

to help you with repairing the bone.

幫助你修補骨頭。

So we take that periosteum layer

我們發展出了一種注射法，

and we developed a way to inject underneath it

在鼓膜底下

a liquid that then, within 30 seconds,

注射一種液體，

would turn into quite a rigid gel

30 秒之內液體就會硬化成膠狀

and can actually lift the periosteum away from the bone.

會把骨膜剝離骨骼

So it creates, in essence, an artificial cavity

實際上，它在骨頭 跟帶有很多幹細胞的這層膜之間

that is right next to both the bone

製造了一個人工腔室，

but also this really rich layer of stem cells.

但同時含有豐富的幹細胞。

And we go in through a pinhole incision

然後我們會從一個 針孔般的切口進入，

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

所以身體的其它細胞不會跑進去，

and what happens is that that artificial in vivo bioreactor cavity

這個人工體內生物反應器

can then lead to the proliferation of these stem cells,

能夠讓這些幹細胞增殖，

and they can form lots of new tissue,

然後它們就可以變成很多新組織，

and then over time, you can harvest that tissue

一段時間過後你就能收集這些細胞

and use it elsewhere in the body.

並用在身體的其他部位。

This is a histology slide

這是我們做這件事當時的

of what we see when we do that,

組織切片，

and essentially what we see

我們所看到的基本上

is very large amounts of bone.

就是很多的骨骼。

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

在這張圖片裡面，你能看到腿的中段，

so the bone marrow,

這是骨髓，

then you can see the original bone,

然後你可以看到原來的骨頭，

and you can see where that original bone finishes,

原本的骨頭到這裡為止，

and just to the left of that is the new bone

左邊的是在這個

that's grown within that bioreactor cavity,

是在生物反應器裡面長出的新骨頭

and you can actually make it even larger.

你也可以讓它長得更大

And that demarcation that you can see

在原來的和新的骨頭之間

between the original bone and the new bone

的界線

acts as a very slight point of weakness,

有著非常微小的脆弱點，

so actually now the surgeon can come along,

外科醫師現在就可以過來

can harvest away that new bone,

將新的骨骼取走，

and the periosteum can grow back,

然後骨膜會長回去，

so you're left with the leg

你的腿

in the same sort of state

在這樣的情況下

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

就像沒做過任何事一樣。

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

所以和髂嵴修補法相比之下，

compared to an iliac crest harvest.

術後幾乎可以說是完全沒有疼痛感。

And you can grow different amounts of bone

你可以借由調整注射膠的量來

depending on how much gel you put in there,

製造出不同量的骨頭，

so it really is an on demand sort of procedure.

所以這個技術確實可以量身訂做。

Now, at the time that we did this,

好，我們做這個計劃時

this received a lot of attention in the press,

這項技術受到了媒體的大量關注，

because it was a really nice way

因為這是

製造新骨骼很棒的方法，

of generating new bone,

and we got many, many contacts

也有很多人跟我們聯絡，

from different people that were interested in using this.

他們對這種方法非常有興趣。

And I'm just going to tell you,

我要讓你們知道的是，

sometimes those contacts are very strange,

有時候這些和我們聯絡的人很奇怪，

slightly unexpected,

甚至有點出乎意料，

and the very most interesting,

我所遇過的

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

最有趣的的聯絡人

was actually from a team of American footballers

是美式足球隊員。

that all wanted to have double-thickness skulls

他們想要有

made on their head.

兩倍厚的頭骨。

And so you do get these kinds of contacts,

就是這樣的一些人

and of course, being British

當然囉，身為一個英國人

and also growing up in France,

並且在法國長大，

I tend to be very blunt,

我必須試著很客氣

and so I had to explain to them very nicely

向他們解釋

that in their particular case,

這裡實在是沒有太多東西需要被保護，

there probably wasn't that much in there

因為

to protect in the first place.

首先沒有足夠的材料去保護他們。

(Laughter)

（笑聲）

(Applause)

（掌聲）

So this was our approach,

這就是我們所用的方法，

and it was simple materials,

材料非常簡單，

but we thought about it carefully.

但是我們深思熟慮。

And actually we know that those cells

我們也確實知道這些 在身體裡、在胚胎裡的細胞

in the body, in the embryo, as they develop

當它們發育之後

can form a different kind of tissue, cartilage,

能變成不同的組織，像是軟骨，

and so we developed a gel that was slightly different

因此我們法展出了一種膠，

in nature and slightly different chemistry,

這種膠和自然存在的不太一樣， 化學性質也不甚相同，

put it in there, and we were able to get

注射進去之後，

100 percent cartilage instead.

我們反而會得到百分之百的軟骨。

And this approach works really well, I think,

我認為這項技術

for pre-planned procedures,

對於有事先規劃的療程非常實用，

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

但是你必須要事先規劃好。

So for other kinds of operations,

因此，對於其他手術來說

there's definitely a need for other

有架構的方法

scaffold-based approaches.

是絕對必須的。

And when you think about designing

當你想要設計

those other scaffolds, actually,

其他的架構時，實際上，

you need a really multi-disciplinary team.

你需要有一個全方位的團隊。

And so our team has chemists,

所以我們的團隊有化學家

it has cell biologists, surgeons, physicists even,

細胞生物學家、外科醫師，甚至是物理學家

and those people all come together

這些人聚在一起，

and we think really hard about designing the materials.

絞盡腦汁才設計出這些材料。

But we want to make them have enough information

我們希望讓他們獲得充足的資訊，

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

讓細胞做到我們期望的，

but not be so complex as to make it difficult

但是不能過於複雜而難以

to get to clinic.

應用在臨床上。

And so one of the things we think about a lot

因此我們想到了

is really trying to understand

要了解人

the structure of the tissues in the body.

人體內組織的結構，

And so if we think of bone,

當我們想到骨骼

obviously my own favorite tissue,

顯然是我最喜歡的組織，

we zoom in, we can see,

放大來看，

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

既使你對它一無所知，

it's beautifully organized, really beautifully organized.

也會看到它是有組織的，非常有組織。

We've lots of blood vessels in there.

裡面有非常多的血管，

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

如果再放大來看，會看到細胞是被

are actually surrounded by a 3D matrix

奈米等級的纖維形成的 3D 結構包圍，

of nano-scale fibers, and they give a lot

這些纖維會

of information to the cells.

提供細胞很多訊息。

And if we zoom in again,

再放大，在骨頭的例子中

actually in the case of bone, the matrix

包圍細胞的胞外物質，

around the cells is beautifully organized

形成了非常有組織

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

的奈米結構，

that's part organic, part inorganic.

同時也是兼具有機與無機的結構。

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

那是這個領域的根本，

that has looked at developing materials

也讓我們想到要發展

that have this hybrid kind of structure.

兼具有機與無機的材料。

And so I'm showing here just two examples

我現在要講的兩個例子

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

是我們所製造出並具有相似結構的材料

and you can really tailor it.

而且可以客製化。

You can see here a very squishy one

這個材料質地像糊

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

但是與這種材料混合的另一種材料

but actually has remarkable toughness,

卻具有非同尋常的堅硬度，

and it's no longer brittle.

也不易碎。

And an inorganic material would normally be really brittle,

一般無機材料是易碎的，

and you wouldn't be able to have

也無法擁有

that sort of strength and toughness in it.

如此的力量與韌性。

One other thing I want to quickly mention is that

我想快速帶過另外一件事情，

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

很多我們做出的架構是有孔的， 它們也必須如此，

because you want blood vessels to grow in there.

因為我們希望血管能在其中生長，

But the pores are actually oftentimes

但是這些孔洞常常

much bigger than the cells,

比細胞大上許多，

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,

在細胞看來也是個曲面，

and that's a little bit unnatural.

這件事情不太自然。

And so one of the things you can think about doing

其中一個解決辦法就是，

is actually making scaffolds with slightly different dimensions

讓架構在度量上有點不同，

that might be able to surround your cells in 3D

讓它能夠以 3D 的形式包住細胞

and give them a little bit more information.

然後給它們更多的訊息。

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

在這些領域，許多研究正在進行

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

最後，我想說說把這些東西在

applying this sort of thing to cardiovascular disease,

心血管疾病上的應用，

because this is a really big clinical problem.

因為這些疾病在臨床上相當重要。

And one of the things that we know is that,

我們知道的一件事情是，很不幸的

unfortunately, if you have a heart attack,

如果你有了心肌梗塞，

then that tissue can start to die,

那裡的組織就會開始壞死，

and your outcome may not be very good over time.

長期下來的後果不會太好。

And it would be really great, actually,

如果我們能

if we could stop that dead tissue

阻止組織壞死那就太棒了

either from dying or help it to regenerate.

不論是從阻止壞死或是幫助它再生。

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

現在全世界進行著 非常多的幹細胞試驗，

and they use many different types of cells,

他們用了很多種不同的細胞，

but one common theme that seems to be coming out

但是有一件事情常常發生，

is that actually, very often, those cells will die

那就是這些細胞在被植入

once you've implanted them.

之後就會死亡。

And you can either put them into the heart

你可以把它們放進心臟

or into the blood system,

或是血液系統裡頭，

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

但無論是哪種方法，我們似乎都不能

to get quite the right number of cells

讓細胞

getting to the location we want them to

到達我們希望它們去的部位，

and being able to deliver the sort of beautiful

然後進行美妙的

cell regeneration that we would like to have

細胞再生，

to get good clinical outcomes.

得到良好的療效。

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

因此，我們以及在這個領域的很多人

and many other people in the field are thinking of,

在思考的事情是，

are actually developing materials for that.

發展出能夠做到這些事情的材料。

But there's a difference here.

但是不同的是，

We still need chemistry, we still need mechanics,

我們仍然需要化學、力學，

we still need really interesting topography,

需要很有趣的拓樸學，

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

也需要能夠研究 這些細胞的有趣方法。

But now, the cells also

目前，這些細胞

would probably quite like a material

比較像是

that's going to be able to be conductive,

能夠傳導的材料，

because the cells themselves will respond very well

因為這些細胞 會對訊號做出很好的回應，

and will actually conduct signals between themselves.

並在彼此之間傳遞這些訊號。

You can see them now

你可以看到這些細胞在材料上

beating synchronously on these materials,

同步跳動，

and that's a very, very exciting development

這真的是

that's going on.

令人相當興奮的進展。

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

總而言之，我想說的是

being able to work in this sort of field,

能在這個領域工作，

all of us that work in this field

對在這個領域的所有人來說，

that's not only super-exciting science,

這不只是令人超級興奮的科學，

but also has the potential

也對病人

to impact on patients,

有潛在影響力，

however big or small they are,

不論這些影響是大是小，

is really a great privilege.

都是很好的恩典。

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

在此我也想要感謝你們所有人。

Thank you.

謝謝。

(Applause)

（掌聲）