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LORNA GIBSON: What I thought I
would do today is two things.

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I wanted to give this talk
about osteochondral scaffolds,

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and this is just slides.

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I'm not going to
write anything down.

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So there aren't going
to be any notes.

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And I'll put the slides on the
Stellar site, I don't know,

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00:00:38,890 --> 00:00:40,960
this afternoon or
tonight or something.

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00:00:40,960 --> 00:00:44,282
And this isn't going to take
the whole time we have today,

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00:00:44,282 --> 00:00:45,740
so the other thing
I thought I'd do

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00:00:45,740 --> 00:00:47,880
is I wanted to walk you
through this little booklet

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00:00:47,880 --> 00:00:50,190
that I handed out about
how to write a paper.

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00:00:50,190 --> 00:00:52,060
So this is by Mike
Ashby, who you know,

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00:00:52,060 --> 00:00:53,060
I've written books with.

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00:00:53,060 --> 00:00:55,610
He was my PhD advisor
and we wrote the books

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on cellular solids together.

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00:00:56,930 --> 00:00:58,760
He has written many books.

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00:00:58,760 --> 00:01:00,662
I looked him up on
Amazon this morning,

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and even though I know
he'd written many books,

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I was shocked how many books.

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00:01:03,828 --> 00:01:08,230
They had 58 listings for just
books with him as a co-author

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00:01:08,230 --> 00:01:10,410
and some are second
editions and third editions.

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00:01:10,410 --> 00:01:11,576
He's written a lot of books.

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00:01:11,576 --> 00:01:13,660
He's written a lot
of materials, papers.

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00:01:13,660 --> 00:01:15,310
And he's, in the
materials community,

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00:01:15,310 --> 00:01:19,310
he's seen as a very
clear and lucid writer.

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00:01:19,310 --> 00:01:21,199
So he's written this
thing for his students

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00:01:21,199 --> 00:01:22,990
and I thought we could
just walk through it

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00:01:22,990 --> 00:01:25,236
and I can talk to you a
little bit about writing.

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00:01:25,236 --> 00:01:27,610
Because I know you're not
quite there with your projects,

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00:01:27,610 --> 00:01:29,151
but later on in the
term you're going

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00:01:29,151 --> 00:01:30,670
to want to write
up your project,

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00:01:30,670 --> 00:01:33,740
and it's not too early to
start thinking about writing.

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00:01:33,740 --> 00:01:36,460
And there's some really
good advice and it's short

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00:01:36,460 --> 00:01:38,100
and it's to the point.

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00:01:38,100 --> 00:01:40,341
It's really helpful,
that little brochure.

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00:01:40,341 --> 00:01:41,840
So we won't read
every single thing,

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00:01:41,840 --> 00:01:43,040
but I wanted to kind
of walk through some

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00:01:43,040 --> 00:01:45,150
of the main points in
it, and that pretty much

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00:01:45,150 --> 00:01:46,100
should take the hour.

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00:01:46,100 --> 00:01:48,980
So last time we talked about
tissue engineering scaffolds,

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and today, I wanted
to do a case study,

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00:01:51,740 --> 00:01:53,159
and this was a
project we had here

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00:01:53,159 --> 00:01:55,700
at MIT and in collaboration with
some people in the materials

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00:01:55,700 --> 00:01:57,610
department at
Cambridge University.

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00:01:57,610 --> 00:02:01,290
And we made what we called
an osteochondral scaffold.

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00:02:01,290 --> 00:02:03,410
So osteo means there was
a part for regenerating

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00:02:03,410 --> 00:02:06,150
bone and chondral means there
was a part for regenerating

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00:02:06,150 --> 00:02:07,100
cartilage.

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00:02:07,100 --> 00:02:09,030
And really the point
of the scaffold

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00:02:09,030 --> 00:02:13,280
was to try to repair small
defects in cartilage.

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00:02:13,280 --> 00:02:16,530
And I'll explain why we
did the bone thing as well.

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00:02:16,530 --> 00:02:18,130
So this is just
a little outline.

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I'm going to talk a
little bit about what

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the structure of cartilage is.

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We have a little
schematic of that.

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Then talk about how small
defects in cartilage

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are currently treated.

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So these are things that,
say you're an athlete,

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you might tear some
cartilage, that kind of thing,

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00:02:31,080 --> 00:02:33,530
not like you have osteoarthritis
and you need a new knee.

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00:02:33,530 --> 00:02:34,742
It's not going to do that.

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So I'll talk a little
bit about cartilage

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and the current treatments.

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I'll talk about
some of the things

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we thought about in making
an osteochondral scaffold,

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like what parameters
were important.

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00:02:44,900 --> 00:02:47,440
And we based it on that
collagen-GAG scaffold

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that I talked about last time.

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So the collagen
glycoseaminoglycan

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scaffold that we
talked about last time.

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And what we did
was we had a layer

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that was a collagen based
scaffold for the cartilage

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and we had another
layer that was

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a mineralized version of that.

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And one of the main things
we did in this project

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was figure out how to
mineralize that scaffold.

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00:03:04,260 --> 00:03:07,170
And then we made this two-layer
osteochondral scaffold.

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So I'll talk about that, OK?

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00:03:09,280 --> 00:03:12,030
So are we good?

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00:03:12,030 --> 00:03:15,540
So this is a schematic
of articular cartilage.

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Articular just means it's
in a joint, so between

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like, say, two of
your long bones,

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and there's several regions.

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So this shows both the cartilage
and the bone underneath it.

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And so this top layer is
called the superficial layer,

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00:03:28,930 --> 00:03:30,410
and then there's
a transition zone,

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00:03:30,410 --> 00:03:32,590
and then there's this
deep cartilage here.

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00:03:32,590 --> 00:03:36,040
And the little white lines
represent how the collagen

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is oriented in the cartilage.

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00:03:38,540 --> 00:03:40,380
So the collagen is
oriented, more or less,

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vertically here and then it
becomes more kind of woven

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00:03:43,610 --> 00:03:45,940
and horizontal towards the top.

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00:03:45,940 --> 00:03:48,430
And so those three
different zones,

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the collagen is
oriented differently.

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Then there's a region down
here called the tidemark.

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Everything above here is just
cartilage and everything below

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is calcified to some extent.

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So this next layer down here
it's more cartilage-like,

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00:04:04,780 --> 00:04:09,300
but it's got some
calcification in it as well.

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00:04:09,300 --> 00:04:10,900
And then here's
the compact bone.

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They call it subchondral bone.

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It's the bone below
the cartilage.

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00:04:14,290 --> 00:04:15,890
So chondral is cartilage.

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And then here's the
trabecular bone.

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We talked about trabecular
bone a couple of weeks ago, OK?

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So one of the things is there's
different types of collagen

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and the different types may
have slightly different fiber

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structures or slightly
different compositions.

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They're all related, but they're
slightly different types.

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And bone has what's called
type I collagen and cartilage

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00:04:36,870 --> 00:04:39,460
has type II collagen. So
when we made the scaffold,

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we wanted the bony
layer to be made

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00:04:41,350 --> 00:04:45,140
with type I and the cartilage
layer to be made with type II.

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00:04:45,140 --> 00:04:47,870
So I think with the 3032
people have probably seen it.

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I think I did a
version of this for you

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00:04:49,640 --> 00:04:52,060
guys, didn't I at the
end of term, something?

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00:04:52,060 --> 00:04:56,910
Yeah, but there's other people,
so it's really for them.

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So if you think of
articular cartilage,

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it has difficulty repairing
itself and one of the reasons

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00:05:05,289 --> 00:05:06,830
that it's difficult
for the cartilage

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00:05:06,830 --> 00:05:10,340
to repair itself is that
there's no blood supply in it

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and another reason is that
there's not very many cells.

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So chondrocytes are
the cells in cartilage

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and if there's a low volume
fraction of the cells,

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then it's not so easy for
that small number of cells

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to actually produce the
extracellular matrix, which

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is kind of what you think
of as the cartilage.

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And it can be damaged, either
as I said, from sports injuries,

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typically that's what
young people get,

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they tear their cartilage in
some sporting injury accident,

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or from osteoarthritis.

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00:05:36,500 --> 00:05:38,180
So these scaffolds
we're talking about,

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they're not really meant
to repair large amounts

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of cartilage that are damaged.

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And as I said, the cartilage
has a poor capacity

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for self-repair.

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00:05:48,097 --> 00:05:49,680
So there's several
treatments, there's

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three treatments that
are given currently

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and the most common one is
called marrow stimulation.

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And some of these
orthopedic treatments

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are fairly crude
when you look at it.

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So this marrow stimulation,
what's involved

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is they take a drill.

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So here's the drill.

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And they basically drill
through the cartilage.

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So this would be the
cartilage layer here.

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And they drill
down into the bone

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and they want to get down
into the trabecular bone.

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So they want to go
below the cortical

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or the subchondral bone
and they want to go down

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into the trabecular bone.

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And the reason they want to
do that is the trabecular bone

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has bone marrow in it
and the bone marrow

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has mesenchymal
stem cells, and they

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want those mesenchymal
stem cells to move up

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into the cartilage layer.

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So that's what this
red glob is here.

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The idea is that
you've made a hole

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and now that hole
is going to fill up

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with a blood clot, which will
have these mesenchymal stem

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cells, and that those
will form cartilage.

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So it does work to some
extent, but it's not really

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a great result. There's
something like 75,000

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of these done a year.

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As I said, this is the
most common kind of repair.

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The next most sophisticated
type of repair, what they do

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00:06:58,580 --> 00:07:01,650
is they take plugs of bone and
cartilage from another place.

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00:07:01,650 --> 00:07:03,080
So say this is
where the defect is

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00:07:03,080 --> 00:07:04,660
and they want to repair that.

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00:07:04,660 --> 00:07:07,240
They take bone and cartilage
from this spot up here.

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So they sort of drill out
little cylindrical cores

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00:07:10,040 --> 00:07:12,510
and then they plug them
into this bit here.

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And that's called an
osteochondral autograft.

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00:07:15,380 --> 00:07:17,550
Sometimes it's
called mosaicplasty

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because they build up a
little mosaic from all

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those little pieces.

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And then they just
leave these donor sites,

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where they took the plugs from,
they just leave those empty.

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00:07:26,550 --> 00:07:30,650
So they try to take the bone
and cartilage from regions where

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the loads are lower,
but they end up

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leaving holes, which
is not so desirable.

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00:07:35,990 --> 00:07:38,370
And again, those holes
may fill a little bit

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00:07:38,370 --> 00:07:42,600
by the previous mechanism.

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Then the most fancy
method that they use now

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00:07:45,820 --> 00:07:48,860
is called autologous
chondrocyte implantation.

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So what they do is they
harvest cartilage cells

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from the patient.

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They then take them to a
lab and they culture them

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00:07:55,040 --> 00:07:56,560
for two or three
weeks and they get

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00:07:56,560 --> 00:07:59,370
them to multiply and
proliferate and grow

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and then they
re-implant the cells.

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So this works fairly
well, but the difficulty

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00:08:05,930 --> 00:08:09,090
is it involves two surgeries,
so one to get the cells out

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and one to put them
back in, and there's

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00:08:11,190 --> 00:08:12,619
the cost of the cell culture.

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00:08:12,619 --> 00:08:15,160
So this is a much more expensive
procedure because of the two

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surgeries and the cost of
doing the cell culture,

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but I think it's the
method that works the best.

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And when I talked about this in
3032, I mentioned Dara Torres.

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Dara Torres is an
Olympic swimmer.

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She's 47.

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She began swimming
in the Olympics

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00:08:30,550 --> 00:08:33,370
in 1984, more than 30 years ago.

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00:08:33,370 --> 00:08:35,039
And she has swum
in the Olympics,

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00:08:35,039 --> 00:08:37,750
not every one,
but up until 2008.

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00:08:37,750 --> 00:08:40,669
And even 2008, she won
three silvers that year.

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She was, I think,
the oldest person

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00:08:42,299 --> 00:08:44,740
who's ever won a
medal in the Olympics.

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And she had this surgery done
at the Brigham a few years ago.

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00:08:49,420 --> 00:08:51,054
And it used to be,
they've stopped

218
00:08:51,054 --> 00:08:53,220
running these commercials
but the Brigham for a time

219
00:08:53,220 --> 00:08:56,070
was running these commercials,
that featured Dara Torres

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00:08:56,070 --> 00:09:00,270
and saying basically that she
had this surgery done there.

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00:09:00,270 --> 00:09:03,180
I'm assuming she
was happy with it.

222
00:09:03,180 --> 00:09:05,526
OK, so that's what
they do currently

223
00:09:05,526 --> 00:09:08,150
and what we were thinking of and
what other groups have thought

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00:09:08,150 --> 00:09:12,480
about is could you repair
damage in the cartilage

225
00:09:12,480 --> 00:09:14,860
by using a tissue
engineering scaffold?

226
00:09:14,860 --> 00:09:16,360
So what we were
thinking about when

227
00:09:16,360 --> 00:09:19,750
we tried to do
this project was we

228
00:09:19,750 --> 00:09:23,130
wanted to use a healthy
articular cartilage joint

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00:09:23,130 --> 00:09:25,740
as a model for our scaffold.

230
00:09:25,740 --> 00:09:29,260
We wanted to have a layer that
would go down into the bone

231
00:09:29,260 --> 00:09:32,100
so that you would have access
to those mesenchymal stem cells.

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And that's why we wanted
an osteochondral scaffold,

233
00:09:34,780 --> 00:09:37,190
so that we would have a
layer for the cartilage

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00:09:37,190 --> 00:09:39,730
but also a layer that would
go down into the bone.

235
00:09:39,730 --> 00:09:42,810
We wanted to be able to control
scaffold parameters, things

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00:09:42,810 --> 00:09:45,460
like the mineral content
and the pore size.

237
00:09:45,460 --> 00:09:47,970
Remember, I said these
tissue engineering scaffolds,

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00:09:47,970 --> 00:09:49,750
the pore size is one
of the parameters,

239
00:09:49,750 --> 00:09:53,080
that you want to have the
pore size in a certain range.

240
00:09:53,080 --> 00:09:54,700
And we wanted to
use materials that

241
00:09:54,700 --> 00:09:57,990
would be appropriate
for approval

242
00:09:57,990 --> 00:09:59,711
from things like the FDA.

243
00:09:59,711 --> 00:10:02,210
So typically, when people make
tissue engineering scaffolds,

244
00:10:02,210 --> 00:10:03,660
they don't start with
some material that's

245
00:10:03,660 --> 00:10:04,650
never been approved before.

246
00:10:04,650 --> 00:10:05,800
They start with
something that already

247
00:10:05,800 --> 00:10:07,550
has approval for
something else and that's

248
00:10:07,550 --> 00:10:09,440
what we wanted to do too.

249
00:10:09,440 --> 00:10:12,500
So this was our idea of
what we wanted the scaffold

250
00:10:12,500 --> 00:10:13,100
to look like.

251
00:10:13,100 --> 00:10:16,380
We wanted an unmineralized type
II collagen scaffold up here

252
00:10:16,380 --> 00:10:17,880
that would be for the cartilage.

253
00:10:17,880 --> 00:10:20,900
We wanted a mineralized type
I collagen scaffold down there

254
00:10:20,900 --> 00:10:22,300
for the bone.

255
00:10:22,300 --> 00:10:23,750
And we wanted some
region that had

256
00:10:23,750 --> 00:10:26,150
some gradient in
mineralization because it

257
00:10:26,150 --> 00:10:28,309
would be like that
layer of cartilage that

258
00:10:28,309 --> 00:10:29,350
was slightly mineralized.

259
00:10:29,350 --> 00:10:31,920
So we wanted to duplicate
that whole structure.

260
00:10:31,920 --> 00:10:34,384
So that was our picture
of what we wanted to do

261
00:10:34,384 --> 00:10:37,050
and we had a pretty good idea of
how we were going to make this.

262
00:10:37,050 --> 00:10:38,841
We were just going to
use that same process

263
00:10:38,841 --> 00:10:41,540
that [INAUDIBLE] developed
for the skin scaffolds.

264
00:10:41,540 --> 00:10:43,000
He was involved
with this project

265
00:10:43,000 --> 00:10:45,760
but just used type II
collagen instead of type I.

266
00:10:45,760 --> 00:10:47,730
The challenge was
really figuring out

267
00:10:47,730 --> 00:10:50,820
how to make the mineralized
collagen scaffold

268
00:10:50,820 --> 00:10:54,410
and then how to get this
gradient in the mineralization

269
00:10:54,410 --> 00:10:56,442
between the two layers.

270
00:10:56,442 --> 00:10:58,150
So this, I think, I
showed you last time.

271
00:10:58,150 --> 00:10:59,899
So this is just the
method we used to make

272
00:10:59,899 --> 00:11:01,220
the collagen-GAG scaffold.

273
00:11:01,220 --> 00:11:04,290
So we take type II collagen.
We put it in acetic acid.

274
00:11:04,290 --> 00:11:06,670
Remember, that destroys
the periodic banding

275
00:11:06,670 --> 00:11:10,880
of the collagen and it improves
the immunological response.

276
00:11:10,880 --> 00:11:13,440
We add the chondroitin
6-sulfate, the GAG,

277
00:11:13,440 --> 00:11:14,640
to crosslink it.

278
00:11:14,640 --> 00:11:16,800
We then just make a
slurry out of that.

279
00:11:16,800 --> 00:11:18,000
So we mix that all together.

280
00:11:18,000 --> 00:11:19,640
We keep it as a slurry.

281
00:11:19,640 --> 00:11:21,490
And then the second
stage is you put

282
00:11:21,490 --> 00:11:24,200
the slurry or the
suspension into a pan,

283
00:11:24,200 --> 00:11:25,970
and then you do the
freeze drying process.

284
00:11:25,970 --> 00:11:27,469
So you go through
this process where

285
00:11:27,469 --> 00:11:29,200
you start at this
room temperature

286
00:11:29,200 --> 00:11:30,660
and atmospheric pressure.

287
00:11:30,660 --> 00:11:33,290
You cool it down to freeze
it, and then you sublimate it,

288
00:11:33,290 --> 00:11:38,560
and you're left with a very
porous collagen-GAG scaffold.

289
00:11:38,560 --> 00:11:39,700
So these are pictures.

290
00:11:39,700 --> 00:11:41,370
I think this was with
a type I collagen,

291
00:11:41,370 --> 00:11:44,120
but it looks the same
with the type II collagen.

292
00:11:44,120 --> 00:11:47,251
So that's what the
structure looks like.

293
00:11:47,251 --> 00:11:48,750
I think I showed
you this last time.

294
00:11:48,750 --> 00:11:51,120
We can control the pore
size by controlling

295
00:11:51,120 --> 00:11:52,540
the freezing temperature.

296
00:11:52,540 --> 00:11:54,020
So the way the
freeze dryer works

297
00:11:54,020 --> 00:11:56,880
is there is shelves that
you put these pans on,

298
00:11:56,880 --> 00:11:59,909
and these cooling elements
go through the shelves,

299
00:11:59,909 --> 00:12:01,950
and you can set the
temperature of those shelves.

300
00:12:01,950 --> 00:12:05,300
So we would set the
temperature of those shelves

301
00:12:05,300 --> 00:12:07,822
to different values and we
got different pore sizes.

302
00:12:07,822 --> 00:12:09,280
So the colder the
shelf temperature

303
00:12:09,280 --> 00:12:14,330
was, the faster the
freezing, and the smaller

304
00:12:14,330 --> 00:12:16,130
the size of the ice
grains, and then

305
00:12:16,130 --> 00:12:19,010
the smaller the
size of the pores.

306
00:12:19,010 --> 00:12:21,280
And this is just the
mechanical response again.

307
00:12:21,280 --> 00:12:23,350
So we did mechanical
tests on it.

308
00:12:23,350 --> 00:12:26,010
These are some of the
numbers for the properties.

309
00:12:26,010 --> 00:12:27,900
So we tested it
dry and wet, and we

310
00:12:27,900 --> 00:12:30,391
measured a modulus and a
buckling collapse stress

311
00:12:30,391 --> 00:12:30,890
for it.

312
00:12:30,890 --> 00:12:33,560
So those are just
some values there.

313
00:12:33,560 --> 00:12:36,440
And then it came to making
the mineralized collagen-GAG

314
00:12:36,440 --> 00:12:40,250
scaffold, and one of the
students in Cambridge, England

315
00:12:40,250 --> 00:12:43,937
was really the main person
who did this, Andrew Lynn.

316
00:12:43,937 --> 00:12:45,520
And he worked with
Brendan Harley, who

317
00:12:45,520 --> 00:12:48,290
was our student here,
and after they graduated,

318
00:12:48,290 --> 00:12:49,900
I had another student,
Biraja Kanungo,

319
00:12:49,900 --> 00:12:51,370
who worked on this too.

320
00:12:51,370 --> 00:12:53,790
So Andrew Lynn really
developed this technique.

321
00:12:53,790 --> 00:12:56,260
And this involved taking
the collagen and the GAG, so

322
00:12:56,260 --> 00:12:58,185
the same as for
the other scaffold,

323
00:12:58,185 --> 00:13:00,560
but this time, if we want to
make a mineralized scaffold,

324
00:13:00,560 --> 00:13:02,850
we somehow have to get
calcium phosphate into it.

325
00:13:02,850 --> 00:13:05,760
So it's got to have sort of
a hydroxyapatite-ish type

326
00:13:05,760 --> 00:13:07,940
of component to it.

327
00:13:07,940 --> 00:13:12,180
So this time we used phosphoric
acid instead of the acetic acid

328
00:13:12,180 --> 00:13:15,680
and we put some calcium salts
into the mixture as well.

329
00:13:15,680 --> 00:13:18,820
And Andrew was really the one
who figured out how to do this

330
00:13:18,820 --> 00:13:20,350
and what salts to use.

331
00:13:20,350 --> 00:13:21,970
And then the process
was very similar.

332
00:13:21,970 --> 00:13:23,330
So we have this slurry.

333
00:13:23,330 --> 00:13:24,830
We mix the slurry up.

334
00:13:24,830 --> 00:13:27,110
We did a freeze drying
process, and then we

335
00:13:27,110 --> 00:13:29,980
crosslinked it with a chemical
crosslinker called EDAC.

336
00:13:29,980 --> 00:13:31,950
So it's just a chemical
that you put into this

337
00:13:31,950 --> 00:13:33,560
and it crosslinks it all.

338
00:13:33,560 --> 00:13:37,350
So that was how we made
the mineralized scaffold.

339
00:13:37,350 --> 00:13:39,640
The mineral we got was
something called brushite,

340
00:13:39,640 --> 00:13:41,890
which is a calcium phosphate,
but it's not exactly

341
00:13:41,890 --> 00:13:43,840
the same as hydroxyapatite.

342
00:13:43,840 --> 00:13:46,590
And we could control
the amount of brushite

343
00:13:46,590 --> 00:13:48,840
by different weight
fractions or volume fractions

344
00:13:48,840 --> 00:13:51,190
by controlling how much of
the calcium salts we put in

345
00:13:51,190 --> 00:13:54,630
and what the molarity of
the phosphoric acid was.

346
00:13:54,630 --> 00:13:56,670
If you take brushite
and you put it in water,

347
00:13:56,670 --> 00:13:59,040
it then converts to
octacalcium phosphate

348
00:13:59,040 --> 00:14:01,900
and then to apatite by
a hydrolytic conversion.

349
00:14:01,900 --> 00:14:06,360
So the apatite is related to
the hydroxyapatite in bone.

350
00:14:06,360 --> 00:14:08,670
And this was the structure
of the mineralized scaffold

351
00:14:08,670 --> 00:14:09,610
that we got.

352
00:14:09,610 --> 00:14:11,360
So you can see it looks
a little different

353
00:14:11,360 --> 00:14:13,440
from the collagen-GAG scaffold.

354
00:14:13,440 --> 00:14:14,380
It's much denser.

355
00:14:14,380 --> 00:14:17,220
Typically, the densities
were like 5% or 10% dense.

356
00:14:17,220 --> 00:14:19,740
And remember, the collagen
scaffold was 0.5% dense.

357
00:14:19,740 --> 00:14:21,529
So it's a lot denser.

358
00:14:21,529 --> 00:14:23,820
But if you notice, there's
a few things to notice here.

359
00:14:23,820 --> 00:14:27,300
So one is the pore size,
that's a 500 micron bar.

360
00:14:27,300 --> 00:14:31,000
And we could make pores between
about 50 and 1,000 microns,

361
00:14:31,000 --> 00:14:32,980
depending on the
freezing conditions.

362
00:14:32,980 --> 00:14:35,190
And the range of pore
sizes we were shooting for

363
00:14:35,190 --> 00:14:36,860
was somewhere
between 100 and 500,

364
00:14:36,860 --> 00:14:38,390
so we could get in the
right ballpark with that.

365
00:14:38,390 --> 00:14:40,306
And you can see, just
looking at that picture,

366
00:14:40,306 --> 00:14:42,200
if that's 500
microns, those pores

367
00:14:42,200 --> 00:14:44,400
are somewhere of that order.

368
00:14:44,400 --> 00:14:47,480
Another thing to look
at is this image here,

369
00:14:47,480 --> 00:14:50,000
and this just shows,
the white little dots

370
00:14:50,000 --> 00:14:52,500
are the calcium
phosphate mineral,

371
00:14:52,500 --> 00:14:53,980
and it just shows
that the mineral

372
00:14:53,980 --> 00:14:56,240
is uniformly distributed
throughout the thickness

373
00:14:56,240 --> 00:14:57,430
of the scaffold.

374
00:14:57,430 --> 00:15:00,330
So some people had tried to make
scaffolds for regenerating bone

375
00:15:00,330 --> 00:15:03,200
where they take, say,
one of those polymers

376
00:15:03,200 --> 00:15:05,060
for resorbable sutures
or they take collagen

377
00:15:05,060 --> 00:15:07,460
and they coat it
with hydroxyapatite,

378
00:15:07,460 --> 00:15:11,230
but the shortcoming of that
is that the scaffold is

379
00:15:11,230 --> 00:15:12,519
going to resorb over time.

380
00:15:12,519 --> 00:15:14,810
The cells are going to secrete
enzymes, which are going

381
00:15:14,810 --> 00:15:16,420
to eat away at the scaffold.

382
00:15:16,420 --> 00:15:18,350
And if the scaffold
resorbs, you're

383
00:15:18,350 --> 00:15:20,110
eating away at the
hydroxyapatite first

384
00:15:20,110 --> 00:15:21,526
and then you're
left with whatever

385
00:15:21,526 --> 00:15:23,050
polymer is underneath that.

386
00:15:23,050 --> 00:15:26,032
Whereas this gives you a
more uniform composition

387
00:15:26,032 --> 00:15:27,740
throughout the thickness
of the scaffold,

388
00:15:27,740 --> 00:15:29,870
and you've got calcium
phosphate everywhere

389
00:15:29,870 --> 00:15:32,880
throughout the thickness of
the struts in the scaffold.

390
00:15:32,880 --> 00:15:35,470
So that's the structure of that.

391
00:15:35,470 --> 00:15:38,550
We wanted to make sure that
the mineral was uniformly

392
00:15:38,550 --> 00:15:40,840
distributed throughout
the scaffold,

393
00:15:40,840 --> 00:15:43,390
and we did some micro-CT
imaging, some micro computer

394
00:15:43,390 --> 00:15:44,700
tomography.

395
00:15:44,700 --> 00:15:47,100
And this is our sample
here, and this red line just

396
00:15:47,100 --> 00:15:51,300
says that is the plane at
which this image was taken,

397
00:15:51,300 --> 00:15:53,170
and the black is the mineral.

398
00:15:53,170 --> 00:15:55,640
And then here's a lower plane
and here's another image.

399
00:15:55,640 --> 00:15:58,540
And you can see the calcium
phosphate's pretty uniformly

400
00:15:58,540 --> 00:16:02,020
distributed throughout
that specimen there.

401
00:16:02,020 --> 00:16:05,860
And this was just another way of
looking at the same thing using

402
00:16:05,860 --> 00:16:08,924
EDX in an SEM to look
at where the calcium was

403
00:16:08,924 --> 00:16:10,090
and where the phosphate was.

404
00:16:10,090 --> 00:16:13,830
So again, this is uniform
distribution of the mineral.

405
00:16:13,830 --> 00:16:16,530
We did mechanical tests
on these scaffold as well.

406
00:16:16,530 --> 00:16:19,437
So we measured moduli
and collapse stresses.

407
00:16:19,437 --> 00:16:21,520
We get the same kind of
stress strain curve as all

408
00:16:21,520 --> 00:16:24,340
these other cellular solids.

409
00:16:24,340 --> 00:16:26,560
This was done by-
Biraja Kanungo was

410
00:16:26,560 --> 00:16:29,220
the student who did this bit.

411
00:16:29,220 --> 00:16:31,590
One of the things
we found was that

412
00:16:31,590 --> 00:16:33,510
with these mineralized
scaffolds you

413
00:16:33,510 --> 00:16:35,290
could manually compress them.

414
00:16:35,290 --> 00:16:38,300
If you pushed them down
and you hydrated them,

415
00:16:38,300 --> 00:16:40,970
they would recover
all the deformation,

416
00:16:40,970 --> 00:16:42,730
but we were increased
in improving

417
00:16:42,730 --> 00:16:45,820
the mechanical properties
of the mineralized scaffold

418
00:16:45,820 --> 00:16:48,250
for improved handling
during surgery.

419
00:16:48,250 --> 00:16:51,610
And there's another reason
that I'll get to as well.

420
00:16:51,610 --> 00:16:54,230
So the second reason
is that, if you

421
00:16:54,230 --> 00:16:56,140
look at how bone
itself forms, it

422
00:16:56,140 --> 00:17:01,964
forms from a collagen
precursor, so bone in your body.

423
00:17:01,964 --> 00:17:03,505
And there's something
called osteoid,

424
00:17:03,505 --> 00:17:07,470
which is this collagen-based
precursor to bone,

425
00:17:07,470 --> 00:17:11,569
and it has a modulus of
about 25 to 40 kilopascals

426
00:17:11,569 --> 00:17:14,880
and Angler showed that if you
have mesenchymal stem cells

427
00:17:14,880 --> 00:17:17,230
and you put them on substrates
of different stiffnesses,

428
00:17:17,230 --> 00:17:19,637
they differentiate into
different kinds of cells,

429
00:17:19,637 --> 00:17:21,470
depending on the stiffness
of the substrate.

430
00:17:21,470 --> 00:17:23,980
So the substrate stiffness
can affect what kind of cells

431
00:17:23,980 --> 00:17:25,075
you get.

432
00:17:25,075 --> 00:17:26,700
And the idea here
was we thought, well,

433
00:17:26,700 --> 00:17:29,960
if we could get a stiffness that
was close to this osteoid, what

434
00:17:29,960 --> 00:17:32,620
the natural bone
formation has, then

435
00:17:32,620 --> 00:17:34,670
that might help the
mesenchymal stem

436
00:17:34,670 --> 00:17:37,490
cells differentiate
into the bony cells

437
00:17:37,490 --> 00:17:38,510
that we want them to.

438
00:17:38,510 --> 00:17:40,700
So we wanted to try to
reach a stiffness of this

439
00:17:40,700 --> 00:17:42,020
in the wet state.

440
00:17:42,020 --> 00:17:44,160
And if I back up here,
you can see the stiffness

441
00:17:44,160 --> 00:17:47,690
we had was around four in the
wet state, four kilopascals

442
00:17:47,690 --> 00:17:52,040
and we want to get to 30
or 40, something like that.

443
00:17:52,040 --> 00:17:56,100
So these are our
equations for the modeling

444
00:17:56,100 --> 00:17:59,370
of the mineralized scaffold,
the open celled foam

445
00:17:59,370 --> 00:18:02,730
models for the modulus and
for the collapse strength.

446
00:18:02,730 --> 00:18:04,490
So we could change
different things.

447
00:18:04,490 --> 00:18:06,054
We could change the
solid properties

448
00:18:06,054 --> 00:18:07,720
or we could change
the relative density.

449
00:18:07,720 --> 00:18:09,740
The geometry of the
thing is probably not

450
00:18:09,740 --> 00:18:11,116
going to help us too much.

451
00:18:11,116 --> 00:18:12,490
So basically,
that's what we did.

452
00:18:12,490 --> 00:18:15,879
We first started off trying to
increase the mineral content.

453
00:18:15,879 --> 00:18:17,920
We thought if there was
more mineral content that

454
00:18:17,920 --> 00:18:19,160
would make it stiffer.

455
00:18:19,160 --> 00:18:24,210
So Biraja made these more highly
mineralized scaffolds and these

456
00:18:24,210 --> 00:18:27,800
are just some SEM
images of those.

457
00:18:27,800 --> 00:18:30,190
But the thing he found was
that the properties actually

458
00:18:30,190 --> 00:18:32,840
got worse when he had the more
highly mineralized scaffold.

459
00:18:32,840 --> 00:18:35,300
The modulus went down and
the strength went down,

460
00:18:35,300 --> 00:18:37,595
so that wasn't very helpful.

461
00:18:37,595 --> 00:18:39,220
And when he looked
into it more detail,

462
00:18:39,220 --> 00:18:41,490
he found that he had more
voids in the cell walls

463
00:18:41,490 --> 00:18:43,990
and he had more
disconnected walls.

464
00:18:43,990 --> 00:18:45,980
This shows some of
the micrographs,

465
00:18:45,980 --> 00:18:48,220
so this isn't really
very quantitative,

466
00:18:48,220 --> 00:18:49,820
but you can see
there's holes here.

467
00:18:49,820 --> 00:18:51,320
There's a few holes
here, but there

468
00:18:51,320 --> 00:18:54,060
tended to be a bigger volume
fraction of holes in the more

469
00:18:54,060 --> 00:18:57,280
highly mineralized scaffolds
and more walls that

470
00:18:57,280 --> 00:18:58,520
were disconnected.

471
00:18:58,520 --> 00:19:00,780
So we realized increasing
the mineral content wasn't

472
00:19:00,780 --> 00:19:02,204
going to work very well.

473
00:19:02,204 --> 00:19:03,620
And then the second
thing he tried

474
00:19:03,620 --> 00:19:05,630
was increasing the
relative density.

475
00:19:05,630 --> 00:19:10,040
So we started off at this
density of 4 1/2% dense and he

476
00:19:10,040 --> 00:19:13,320
developed a method of increasing
the relative density up

477
00:19:13,320 --> 00:19:16,110
to about almost 20% here.

478
00:19:16,110 --> 00:19:18,090
He did this by, first
of all, he tried

479
00:19:18,090 --> 00:19:20,280
to just mix more
of the constituents

480
00:19:20,280 --> 00:19:22,990
into the slurry, that's kind
of the most obvious thing.

481
00:19:22,990 --> 00:19:24,670
But as you add
more constituents,

482
00:19:24,670 --> 00:19:27,250
it gets harder and harder
to mix the thing up and have

483
00:19:27,250 --> 00:19:29,490
it homogeneously distributed.

484
00:19:29,490 --> 00:19:32,070
So in the end, that's not
how he made these things.

485
00:19:32,070 --> 00:19:34,240
He started with the
starting mixture

486
00:19:34,240 --> 00:19:36,970
and then he had a vacuum system
for sucking water out of it.

487
00:19:36,970 --> 00:19:38,670
So he would reduce
the amount of water,

488
00:19:38,670 --> 00:19:40,780
which essentially increased
the amount of solids

489
00:19:40,780 --> 00:19:41,940
that was in there.

490
00:19:41,940 --> 00:19:44,010
And you can see in
this last one here,

491
00:19:44,010 --> 00:19:46,530
the most dense
scaffold, he was sucking

492
00:19:46,530 --> 00:19:48,940
the water in one
direction, and he sucked it

493
00:19:48,940 --> 00:19:51,420
so much that he was starting
to get the cells collapsing.

494
00:19:51,420 --> 00:19:54,030
So this one here,
these cells that

495
00:19:54,030 --> 00:19:56,071
have this sort of elongated
orientation, that's

496
00:19:56,071 --> 00:19:57,820
because the cells are
starting to collapse

497
00:19:57,820 --> 00:20:00,301
because of the vacuum
that he was applying.

498
00:20:00,301 --> 00:20:02,050
But he could get a
pretty good difference.

499
00:20:02,050 --> 00:20:03,410
This was almost 5%.

500
00:20:03,410 --> 00:20:06,640
That's almost 20%, so
roughly a factor of four.

501
00:20:06,640 --> 00:20:09,550
There are, yeah, four
difference between them.

502
00:20:09,550 --> 00:20:11,320
So then he did
mechanical tests too,

503
00:20:11,320 --> 00:20:13,660
and he measured the
relative density.

504
00:20:13,660 --> 00:20:18,240
Here's the moduli wet
and then the strength dry

505
00:20:18,240 --> 00:20:20,140
and the strength wet.

506
00:20:20,140 --> 00:20:22,350
So you can see here, if
you look at the dry moduli,

507
00:20:22,350 --> 00:20:25,280
for instance, when you go
from this relative density

508
00:20:25,280 --> 00:20:28,970
to that relative density,
from about 14% to 19%,

509
00:20:28,970 --> 00:20:30,910
the modulus actually drops down.

510
00:20:30,910 --> 00:20:32,680
And if you look at the
structure, I think,

511
00:20:32,680 --> 00:20:35,140
it's because you've got this
flattened structure here.

512
00:20:35,140 --> 00:20:37,720
You've collapsed the
cells a bit already.

513
00:20:37,720 --> 00:20:39,810
So there's a maximum
density that you

514
00:20:39,810 --> 00:20:44,510
might want to go to, probably
somewhere around 14% or 15%.

515
00:20:44,510 --> 00:20:46,510
But the wet modulus
we've got here

516
00:20:46,510 --> 00:20:50,110
is around 35 kilopascals, so
that's close to the target

517
00:20:50,110 --> 00:20:50,610
that we had.

518
00:20:50,610 --> 00:20:52,390
It's close to what
we wanted to have.

519
00:20:52,390 --> 00:20:53,940
So one way you
could get the right

520
00:20:53,940 --> 00:20:58,610
or the appropriate modulus
is by increasing the density

521
00:20:58,610 --> 00:21:00,020
to that value.

522
00:21:00,020 --> 00:21:02,630
Another way is by playing
around with the crosslinking.

523
00:21:02,630 --> 00:21:06,020
So those values were for
non-crosslinked scaffolds.

524
00:21:06,020 --> 00:21:10,720
So here, this is the 14% dense
scaffold wet, non-crosslinked

525
00:21:10,720 --> 00:21:13,020
it was around 35 kilopascals.

526
00:21:13,020 --> 00:21:15,370
This is a dehydrothermal
treatment,

527
00:21:15,370 --> 00:21:17,560
just basically heating it up.

528
00:21:17,560 --> 00:21:19,650
It gives you a higher modulus.

529
00:21:19,650 --> 00:21:22,780
And then this is a chemical
crosslinking technique that

530
00:21:22,780 --> 00:21:24,560
increases the modulus again.

531
00:21:24,560 --> 00:21:27,090
So if you put all
of this together,

532
00:21:27,090 --> 00:21:30,930
you can show these results
for the modulus on one table.

533
00:21:30,930 --> 00:21:32,597
So these are all
the wet modulus.

534
00:21:32,597 --> 00:21:34,180
So it's pretty clear
by playing around

535
00:21:34,180 --> 00:21:36,950
with the relative density
and the crosslinking,

536
00:21:36,950 --> 00:21:39,430
that you can get a
scaffold in that range.

537
00:21:39,430 --> 00:21:42,580
And the idea is that that would
help get the mesenchymal stem

538
00:21:42,580 --> 00:21:47,630
cells to differentiate into
these osteoblast-like cells.

539
00:21:47,630 --> 00:21:49,510
So then we wanted to
also see if our models

540
00:21:49,510 --> 00:21:54,030
for the cellular solids could
be applied to this scaffold,

541
00:21:54,030 --> 00:21:56,500
and we needed the
solid properties.

542
00:21:56,500 --> 00:21:59,910
So Kristyn Van Vliet
helped us with this,

543
00:21:59,910 --> 00:22:04,932
and we isolated a single strut,
bonded it to a glass slide,

544
00:22:04,932 --> 00:22:06,640
and, I think, I
mentioned this last time,

545
00:22:06,640 --> 00:22:10,017
we used an AFM tip to then
do a little bending test.

546
00:22:10,017 --> 00:22:11,850
So I think the one I
mentioned last time was

547
00:22:11,850 --> 00:22:13,330
for the collagen-GAG scaffold.

548
00:22:13,330 --> 00:22:16,340
Then we also did the same thing
for the mineralized scaffold.

549
00:22:16,340 --> 00:22:20,390
And here we measured a modulus
of about seven gigapascals,

550
00:22:20,390 --> 00:22:22,010
so that's a dry modulus.

551
00:22:22,010 --> 00:22:23,650
And just for
comparison, the modulus

552
00:22:23,650 --> 00:22:26,190
of the solid and trabecular
bone is something around 18.

553
00:22:26,190 --> 00:22:29,000
So it's lower, but it's
in the same ballpark.

554
00:22:29,000 --> 00:22:31,890
And by nanoindentation,
we measured a strength

555
00:22:31,890 --> 00:22:34,800
of about 200, and that's
similar to what you

556
00:22:34,800 --> 00:22:36,160
would get in trabecular bone.

557
00:22:36,160 --> 00:22:38,410
So the solid in the
struts themselves

558
00:22:38,410 --> 00:22:42,230
is not exactly like trabecular
bone in mechanical properties,

559
00:22:42,230 --> 00:22:44,550
but not too far off.

560
00:22:44,550 --> 00:22:48,520
And then here's a plot of
the scaffold modulus divided

561
00:22:48,520 --> 00:22:51,940
by the solid modulus against
the relative density.

562
00:22:51,940 --> 00:22:56,250
And this line here, the curve,
is a squared relationship.

563
00:22:56,250 --> 00:22:59,540
So that's what we'd expect
for the foam models.

564
00:22:59,540 --> 00:23:00,590
And this is the strength.

565
00:23:00,590 --> 00:23:04,730
These things fail by a
plastic or a brittle failure,

566
00:23:04,730 --> 00:23:09,741
and this curve is a three halves
power with relative density.

567
00:23:09,741 --> 00:23:12,240
And again, that's what you'd
expect from the cellular solids

568
00:23:12,240 --> 00:23:12,740
model.

569
00:23:12,740 --> 00:23:14,530
So that gives you a
reasonable description

570
00:23:14,530 --> 00:23:20,040
of the behavior of the
mineralized scaffold.

571
00:23:20,040 --> 00:23:21,840
So again, these were
the considerations

572
00:23:21,840 --> 00:23:23,740
in trying to make the
osteochondral scaffold.

573
00:23:23,740 --> 00:23:25,080
So now we have a
collagen scaffold

574
00:23:25,080 --> 00:23:26,065
and we have a
mineralized scaffolding,

575
00:23:26,065 --> 00:23:28,470
and we want to put the
two of them together.

576
00:23:28,470 --> 00:23:30,970
So we wanted to use
the joint as a model,

577
00:23:30,970 --> 00:23:33,880
and we wanted to have some
intermediate layer that

578
00:23:33,880 --> 00:23:36,770
had some gradation in
the mineralization.

579
00:23:36,770 --> 00:23:38,840
So that was the next step.

580
00:23:38,840 --> 00:23:41,940
And the way we did
that was we used

581
00:23:41,940 --> 00:23:45,900
what we fancily called
liquid-phase co-synthesis.

582
00:23:45,900 --> 00:23:48,490
This just meant that we took
the mineralized collagen-GAG

583
00:23:48,490 --> 00:23:50,770
slurry, we poured
that into a mold,

584
00:23:50,770 --> 00:23:53,030
and then we poured the
non-mineralized slurry

585
00:23:53,030 --> 00:23:54,306
into the same mold.

586
00:23:54,306 --> 00:23:56,680
And then we just allowed the
two slurries to interdiffuse

587
00:23:56,680 --> 00:23:58,315
for some time period.

588
00:23:58,315 --> 00:23:59,940
And then we did the
freeze drying step.

589
00:23:59,940 --> 00:24:02,450
So the idea was, that if
you poured the one on top

590
00:24:02,450 --> 00:24:04,899
of the other, the
mineralized one is denser

591
00:24:04,899 --> 00:24:06,690
and then you put the
less dense one on top,

592
00:24:06,690 --> 00:24:08,481
but over some period
of time, there will be

593
00:24:08,481 --> 00:24:10,410
some diffusion between the two.

594
00:24:10,410 --> 00:24:12,630
And then we just did
the freeze drying step.

595
00:24:12,630 --> 00:24:14,390
So this is the scaffold
we ended up with.

596
00:24:14,390 --> 00:24:16,810
This is a micro computer
tomography image.

597
00:24:16,810 --> 00:24:19,490
So here's the
collagen-GAG scaffold

598
00:24:19,490 --> 00:24:21,830
for the cartilage
on top, and here's

599
00:24:21,830 --> 00:24:25,870
the mineralized collagen-GAG
calcium phosphate scaffold

600
00:24:25,870 --> 00:24:28,060
on the bottom for the bone.

601
00:24:28,060 --> 00:24:31,920
And that just kind of
shows what it looked like.

602
00:24:31,920 --> 00:24:33,860
The porosities
and the pore sizes

603
00:24:33,860 --> 00:24:37,140
we got, the collagen-GAG
was about 98% porous

604
00:24:37,140 --> 00:24:40,030
and had a pore size
of around 650 microns.

605
00:24:40,030 --> 00:24:43,250
The mineralized scaffold
was 95.5% porous

606
00:24:43,250 --> 00:24:48,192
and had a pore size of
400, roughly, microns.

607
00:24:48,192 --> 00:24:49,650
And then this is
what the structure

608
00:24:49,650 --> 00:24:51,840
looked like in the EDX.

609
00:24:51,840 --> 00:24:54,050
You can see, this is
the collagen-GAG layer,

610
00:24:54,050 --> 00:24:55,800
this is the mineralized
layer, and there's

611
00:24:55,800 --> 00:24:58,770
some zone in between that's
a little bit mineralized, not

612
00:24:58,770 --> 00:25:02,330
as much as the bony layer
but more than the cartilage

613
00:25:02,330 --> 00:25:07,230
layer, and the same
with the phosphorus.

614
00:25:07,230 --> 00:25:12,390
So we have this collagen-GAG
slightly mineralized layer,

615
00:25:12,390 --> 00:25:15,550
and then a more
mineralized layer

616
00:25:15,550 --> 00:25:18,520
And then finally, there was
a student, Scott Vickers,

617
00:25:18,520 --> 00:25:20,680
who worked with Myron
Spector at the Brigham.

618
00:25:20,680 --> 00:25:22,000
And oops, oops.

619
00:25:22,000 --> 00:25:25,460
No, I don't want the
weekly updates, thank you.

620
00:25:25,460 --> 00:25:26,890
Sorry.

621
00:25:26,890 --> 00:25:30,390
Well, let me just
get rid of this.

622
00:25:30,390 --> 00:25:33,680
Oop, where's my
little mousy mouse?

623
00:25:33,680 --> 00:25:34,250
There we go.

624
00:25:34,250 --> 00:25:37,810
OK, so Scott Vickers
worked with Myron Spector,

625
00:25:37,810 --> 00:25:41,360
and Myron had a surgeon who
could do animal studies.

626
00:25:41,360 --> 00:25:43,310
So we did some animal
studies on goats.

627
00:25:43,310 --> 00:25:46,070
I think there were six
goats at the Brigham.

628
00:25:46,070 --> 00:25:49,040
And they took a plug out
of the knee of the goats,

629
00:25:49,040 --> 00:25:50,710
and they put our scaffold in.

630
00:25:50,710 --> 00:25:52,750
So this is one of the
surgeries as they're

631
00:25:52,750 --> 00:25:54,980
about to poke the scaffold in.

632
00:25:54,980 --> 00:25:58,260
And then, Scott waited, I
think it was four months,

633
00:25:58,260 --> 00:26:01,680
and then sacrificed the goats,
and then did the histology.

634
00:26:01,680 --> 00:26:04,460
And this is one of the
images from his PhD.

635
00:26:04,460 --> 00:26:08,110
So this staining shows that
you've got tissue growing in.

636
00:26:08,110 --> 00:26:11,840
The scaffold was where these
little black dotted lines are.

637
00:26:11,840 --> 00:26:14,420
So you had bony tissue
in here, and there

638
00:26:14,420 --> 00:26:17,840
was a cartilage-like
tissue formed at the top.

639
00:26:17,840 --> 00:26:19,940
It wasn't perfect
articular cartilage,

640
00:26:19,940 --> 00:26:23,240
but it was something
similar to that.

641
00:26:23,240 --> 00:26:26,680
And really was as far as we took
the project with the funding

642
00:26:26,680 --> 00:26:27,290
that we had.

643
00:26:27,290 --> 00:26:29,180
We had a-- I don't know if
you remember that-- well, it's

644
00:26:29,180 --> 00:26:30,190
beyond before your time.

645
00:26:30,190 --> 00:26:33,310
But Cambridge and MIT had a
big research collaboration

646
00:26:33,310 --> 00:26:37,120
and the student exchange
was part of that.

647
00:26:37,120 --> 00:26:39,560
And this was done through
that research collaboration

648
00:26:39,560 --> 00:26:41,890
between Cambridge and MIT.

649
00:26:41,890 --> 00:26:45,650
So this was as far as we took
it with that research funding.

650
00:26:45,650 --> 00:26:48,000
Andrew Lynn, who was the
student in Cambridge,

651
00:26:48,000 --> 00:26:49,990
who developed the
mineralized scaffold,

652
00:26:49,990 --> 00:26:52,940
he then started up a company
called Orthomimetics,

653
00:26:52,940 --> 00:26:56,040
and he had longer term
animal studies done,

654
00:26:56,040 --> 00:26:57,730
and he took it a little further.

655
00:26:57,730 --> 00:27:00,860
In Europe, there's something
called CE Mark approval,

656
00:27:00,860 --> 00:27:02,610
and CE Mark approval
means you can

657
00:27:02,610 --> 00:27:05,300
start doing clinical trials.

658
00:27:05,300 --> 00:27:07,060
So he never got FDA
approval for it,

659
00:27:07,060 --> 00:27:10,250
but he got approval to have
clinical trials in Europe.

660
00:27:10,250 --> 00:27:14,450
And the first clinical use
was in February of 2009.

661
00:27:14,450 --> 00:27:17,470
And they started off
using it for the donor

662
00:27:17,470 --> 00:27:19,260
sites for the mosaicplasties.

663
00:27:19,260 --> 00:27:21,060
Remember the second
method I talked about?

664
00:27:21,060 --> 00:27:23,210
They take plugs
out of one region

665
00:27:23,210 --> 00:27:25,750
and put them into the
region with the damage.

666
00:27:25,750 --> 00:27:27,730
So what they were doing
was using our scaffold

667
00:27:27,730 --> 00:27:30,327
to fill up these
donor sites here

668
00:27:30,327 --> 00:27:31,910
and they found that
worked quite well.

669
00:27:31,910 --> 00:27:33,660
And then eventually,
they started using it

670
00:27:33,660 --> 00:27:35,530
for the primary sites as well.

671
00:27:35,530 --> 00:27:40,190
And as of about April a
few years ago, April 2012,

672
00:27:40,190 --> 00:27:43,250
they had treated about
200 people with this.

673
00:27:43,250 --> 00:27:45,913
AUDIENCE: Wait, so why not
just directly start putting it

674
00:27:45,913 --> 00:27:47,769
in the-- why start with the--

675
00:27:47,769 --> 00:27:49,810
LORNA GIBSON: I think
because these were supposed

676
00:27:49,810 --> 00:27:53,270
to be sites that were less
loaded, weren't as highly

677
00:27:53,270 --> 00:27:56,740
stressed, and they thought that
was a more, not as critical

678
00:27:56,740 --> 00:27:57,826
a place to put them in.

679
00:27:57,826 --> 00:27:58,325
Yeah?

680
00:28:02,350 --> 00:28:05,510
AUDIENCE: So what is
different about this scaffold?

681
00:28:05,510 --> 00:28:07,250
Is it the lack of
the dense bone that

682
00:28:07,250 --> 00:28:12,734
allows all of the marrow cells
to migrate up to the cartilage?

683
00:28:12,734 --> 00:28:14,400
LORNA GIBSON: Well,
I think, there's not

684
00:28:14,400 --> 00:28:16,733
that many people that have
made osteochondral scaffolds,

685
00:28:16,733 --> 00:28:19,670
so it's good that we've
got these two layers.

686
00:28:19,670 --> 00:28:23,040
And the idea that you try
to get the stem cells up

687
00:28:23,040 --> 00:28:24,520
into the cartilage.

688
00:28:24,520 --> 00:28:26,310
The stem cells
will differentiate

689
00:28:26,310 --> 00:28:27,720
into the bone or
the cartilage, I

690
00:28:27,720 --> 00:28:30,178
think, partly depending on the
stiffness of the surrounding

691
00:28:30,178 --> 00:28:30,828
tissue.

692
00:28:30,828 --> 00:28:33,352
AUDIENCE: But they don't do
that in normal bone because

693
00:28:33,352 --> 00:28:34,590
of the dense layer?

694
00:28:34,590 --> 00:28:36,726
LORNA GIBSON: No,
I think they would.

695
00:28:36,726 --> 00:28:38,350
But the thing is, I
mean, in some ways,

696
00:28:38,350 --> 00:28:40,620
that very first
technique where you just

697
00:28:40,620 --> 00:28:43,440
drill holes in, I mean, in some
ways, that's what it's counting

698
00:28:43,440 --> 00:28:46,342
on, right, is that the
marrow mesenchymal stem

699
00:28:46,342 --> 00:28:48,550
cells are going to differentiate
either into the bone

700
00:28:48,550 --> 00:28:49,830
or into the cartilage.

701
00:28:49,830 --> 00:28:53,010
But it's just got a hole
to differentiate into.

702
00:28:53,010 --> 00:28:55,190
So this gives the cell
something to attach

703
00:28:55,190 --> 00:28:58,580
to and I think, gives
a better result. Yeah?

704
00:28:58,580 --> 00:29:01,340
AUDIENCE: So is part of
the scaffold and this bone,

705
00:29:01,340 --> 00:29:03,640
are they removing
the original bone?

706
00:29:03,640 --> 00:29:05,630
LORNA GIBSON: Yeah,
they remove-- yeah.

707
00:29:05,630 --> 00:29:06,600
Let me back up a step.

708
00:29:06,600 --> 00:29:08,850
So when they do this thing
here, so this is in a goat,

709
00:29:08,850 --> 00:29:10,724
but they would do the
same thing in a person.

710
00:29:10,724 --> 00:29:13,050
So when they drill the
hole to put that in, they

711
00:29:13,050 --> 00:29:15,620
go through the cartilage, they
go through the compact bone,

712
00:29:15,620 --> 00:29:18,010
the dense bone, and they go
into the trabecular bone,

713
00:29:18,010 --> 00:29:19,843
because you don't really
get into the marrow

714
00:29:19,843 --> 00:29:23,030
until you're in the pores
of the trabecular bone.

715
00:29:23,030 --> 00:29:23,660
OK?

716
00:29:23,660 --> 00:29:24,890
Are we good?

717
00:29:24,890 --> 00:29:26,361
AUDIENCE: How do they attach it?

718
00:29:26,361 --> 00:29:27,860
LORNA GIBSON: How
do they attach it?

719
00:29:27,860 --> 00:29:28,270
AUDIENCE: Yes.

720
00:29:28,270 --> 00:29:30,103
LORNA GIBSON: I think
it's just a press fit.

721
00:29:30,103 --> 00:29:32,590
I think they just drill
a hole and stick it in.

722
00:29:32,590 --> 00:29:34,340
And these are all
in joints, right?

723
00:29:34,340 --> 00:29:36,710
So there's always another
bone pressing against it.

724
00:29:36,710 --> 00:29:39,530
I mean, in the surgery,
they kind of peel things

725
00:29:39,530 --> 00:29:42,380
apart so they can do the
surgery but there's another bone

726
00:29:42,380 --> 00:29:43,320
pressing down on it.

727
00:29:43,320 --> 00:29:46,930
So I don't think there
was any glue or anything.

728
00:29:46,930 --> 00:29:48,480
So there's that.

729
00:29:48,480 --> 00:29:50,320
So this is just a summary.

730
00:29:50,320 --> 00:29:52,580
So we were able to make
this two-layer scaffold

731
00:29:52,580 --> 00:29:54,691
with a gradient
interface, and we

732
00:29:54,691 --> 00:29:56,190
tried to make it
so that it mimicked

733
00:29:56,190 --> 00:29:58,130
the osteochondral tissues.

734
00:29:58,130 --> 00:30:00,040
And this freeze
drawing process allowed

735
00:30:00,040 --> 00:30:02,270
us to control things
like the mineral content,

736
00:30:02,270 --> 00:30:04,161
the porosity, the pore sizes.

737
00:30:04,161 --> 00:30:06,160
And then we used materials
that had already been

738
00:30:06,160 --> 00:30:08,470
approved for medical devices.

739
00:30:08,470 --> 00:30:11,002
And this was funded
by a number of places.

740
00:30:11,002 --> 00:30:13,210
So the Cambridge MIT Institute
was that collaboration

741
00:30:13,210 --> 00:30:13,710
I mentioned.

742
00:30:13,710 --> 00:30:15,632
I have a chair and I
used some money for that.

743
00:30:15,632 --> 00:30:17,590
Brendan Harley was one
of the students involved

744
00:30:17,590 --> 00:30:19,550
and he got a
fellowship from MIT.

745
00:30:19,550 --> 00:30:23,470
And Andrew Lynn got a
fellowship through the Cambridge

746
00:30:23,470 --> 00:30:26,580
Commonwealth Trust and
through St. John's College

747
00:30:26,580 --> 00:30:28,220
in Cambridge, that's
his college there.

748
00:30:28,220 --> 00:30:30,420
So he had had
funding through that.

749
00:30:30,420 --> 00:30:32,300
So I think that's
the end of that talk.

750
00:30:32,300 --> 00:30:34,700
So are we good with scaffolds?

751
00:30:34,700 --> 00:30:36,909
Yeah, you're good?

752
00:30:36,909 --> 00:30:38,575
So obviously, this
probably whole course

753
00:30:38,575 --> 00:30:40,120
is on tissue engineering.

754
00:30:40,120 --> 00:30:41,670
This is just
scratching the surface

755
00:30:41,670 --> 00:30:43,392
and giving you an
introduction to it,

756
00:30:43,392 --> 00:30:45,600
but I wanted to show you
how a lot of these scaffolds

757
00:30:45,600 --> 00:30:48,600
look a lot like the foamy
materials that I work on,

758
00:30:48,600 --> 00:30:51,930
and that you can use the
same models for trying

759
00:30:51,930 --> 00:30:54,470
to understand the mechanical
properties of the scaffold.

760
00:30:54,470 --> 00:30:57,690
And even though the scaffolds
are acting in a biological way,

761
00:30:57,690 --> 00:31:00,270
there's actually a connection
between the mechanical behavior

762
00:31:00,270 --> 00:31:03,410
of the scaffolds and
the biological response.

763
00:31:03,410 --> 00:31:09,320
So I'm going to talk on
Monday about cell/scaffold

764
00:31:09,320 --> 00:31:13,930
interactions, so
how the environment

765
00:31:13,930 --> 00:31:17,140
biological cells are in
can affect how they behave.

766
00:31:17,140 --> 00:31:19,390
So we're going to talk about
things like cell adhesion

767
00:31:19,390 --> 00:31:22,260
and cell migration
and cell contraction,

768
00:31:22,260 --> 00:31:23,690
contractile behavior.

769
00:31:23,690 --> 00:31:26,302
So I've got another talk
a little bit like this

770
00:31:26,302 --> 00:31:28,010
and that means I'll
have a few notes I'll

771
00:31:28,010 --> 00:31:30,090
put on the board
on Monday about how

772
00:31:30,090 --> 00:31:33,460
the environment that the cells
are in affects how they behave,

773
00:31:33,460 --> 00:31:34,080
OK?

774
00:31:34,080 --> 00:31:36,530
So this is leading up to that.

775
00:31:36,530 --> 00:31:38,269
It's sort of a similar thing.

776
00:31:38,269 --> 00:31:39,810
So I thought for
the rest of the time

777
00:31:39,810 --> 00:31:43,130
today, because I knew this
was going to end early,

778
00:31:43,130 --> 00:31:46,840
I thought what I would
do is just switch gears

779
00:31:46,840 --> 00:31:49,020
and talk about writing.

780
00:31:49,020 --> 00:31:50,956
So normally when
I give a class, I

781
00:31:50,956 --> 00:31:52,580
don't talk about
writing all that much.

782
00:31:52,580 --> 00:31:54,940
I talk about the
technical stuff.

783
00:31:54,940 --> 00:31:58,230
But it turns out writing is
actually a huge part of what

784
00:31:58,230 --> 00:32:02,250
scientists do and engineers do
and whether or not you end up

785
00:32:02,250 --> 00:32:04,475
with an academic job
or a job in industry

786
00:32:04,475 --> 00:32:06,600
or working for government,
no matter where you are,

787
00:32:06,600 --> 00:32:08,300
you are going to
have to write things.

788
00:32:08,300 --> 00:32:10,800
And the better you write, the
better off you're going to be.

789
00:32:10,800 --> 00:32:14,720
So I made copies
of this brochure

790
00:32:14,720 --> 00:32:16,809
and I have a few little slides.

791
00:32:16,809 --> 00:32:18,850
And you're going to have
to write up your project

792
00:32:18,850 --> 00:32:25,240
report for me, and I thought
it might be helpful to just go

793
00:32:25,240 --> 00:32:26,936
through this little brochure.

794
00:32:26,936 --> 00:32:28,810
So I'm not going to
write stuff on the board.

795
00:32:28,810 --> 00:32:31,040
Everything is pretty
much in this brochure,

796
00:32:31,040 --> 00:32:32,930
but I thought I'd just
walk you through some

797
00:32:32,930 --> 00:32:33,930
of the main parts of it.

798
00:32:33,930 --> 00:32:34,780
Oh, did you get one?

799
00:32:34,780 --> 00:32:35,830
Here, have one.

800
00:32:39,970 --> 00:32:42,470
So you might want to think about
this when you're writing up

801
00:32:42,470 --> 00:32:45,180
your project report
for this class,

802
00:32:45,180 --> 00:32:46,860
but this really
is, it's general.

803
00:32:46,860 --> 00:32:49,068
It's really for any time
you have to write something.

804
00:32:49,068 --> 00:32:50,870
This is helpful.

805
00:32:50,870 --> 00:32:52,576
So Mike Ashby put this together.

806
00:32:52,576 --> 00:32:54,950
And as I mentioned, he's done
a lot of scientific writing

807
00:32:54,950 --> 00:32:57,830
and especially in material
science and engineering.

808
00:32:57,830 --> 00:32:59,267
He also makes paintings.

809
00:32:59,267 --> 00:33:00,850
This is one of Mike's
little paintings

810
00:33:00,850 --> 00:33:02,950
of him writing a paper.

811
00:33:02,950 --> 00:33:07,920
And what I was going to do
is just walk through it.

812
00:33:07,920 --> 00:33:11,010
So there's just a few
figures, and mostly it's text,

813
00:33:11,010 --> 00:33:12,960
but let me go through
some of the figures.

814
00:33:12,960 --> 00:33:18,110
So I'm going to just turn
to what's page three, OK?

815
00:33:18,110 --> 00:33:20,890
So one of the things
that he says to start,

816
00:33:20,890 --> 00:33:22,870
and I think this
makes a lot of sense,

817
00:33:22,870 --> 00:33:26,236
is that you can think of
writing a paper the same way you

818
00:33:26,236 --> 00:33:28,360
can think about designing
something in engineering.

819
00:33:28,360 --> 00:33:30,290
So when you think
about design, there's

820
00:33:30,290 --> 00:33:31,750
different stages
of design, right?

821
00:33:31,750 --> 00:33:36,282
There's a conceptual design,
where you just decide roughly

822
00:33:36,282 --> 00:33:37,490
what the thing's going to be.

823
00:33:37,490 --> 00:33:39,480
There's embodiment,
where you work out

824
00:33:39,480 --> 00:33:43,310
a lot of the more details.

825
00:33:43,310 --> 00:33:46,380
You design one version of it.

826
00:33:46,380 --> 00:33:48,340
And then there's the
detailed design, where

827
00:33:48,340 --> 00:33:50,770
you do all the fine-tuning.

828
00:33:50,770 --> 00:33:53,310
You do all the
final design things.

829
00:33:53,310 --> 00:33:55,030
And before you really
start your design,

830
00:33:55,030 --> 00:33:57,071
if you were going to design
an engineering thing,

831
00:33:57,071 --> 00:33:59,540
you would first of all think
about what's the market.

832
00:33:59,540 --> 00:34:02,349
And if you're writing, the
market is your readers.

833
00:34:02,349 --> 00:34:04,640
And so when you think about
what you're going to write,

834
00:34:04,640 --> 00:34:06,598
you have to think about
who's going to read it.

835
00:34:06,598 --> 00:34:08,820
And it's the same thing
when I give a talk.

836
00:34:08,820 --> 00:34:12,560
When I give a talk, before I
make a single PowerPoint slide,

837
00:34:12,560 --> 00:34:14,940
the first thing I think
about is who am I talking to

838
00:34:14,940 --> 00:34:16,690
and what do they already know?

839
00:34:16,690 --> 00:34:18,530
What's the audience?

840
00:34:18,530 --> 00:34:20,760
What are they looking
to get out of the talk?

841
00:34:20,760 --> 00:34:23,174
What am I trying to
convey in the talk?

842
00:34:23,174 --> 00:34:24,590
And the writing
is the same thing.

843
00:34:24,590 --> 00:34:26,469
You have to think
about your audience.

844
00:34:26,469 --> 00:34:30,590
So for instance, I
have technical talks.

845
00:34:30,590 --> 00:34:33,440
Obviously, I go give
technical talks at meetings,

846
00:34:33,440 --> 00:34:35,010
but I do other
sorts of talks too.

847
00:34:35,010 --> 00:34:36,218
I've got the woodpecker talk.

848
00:34:36,218 --> 00:34:38,760
I go give the woodpecker
talk at the Mass Audubon.

849
00:34:38,760 --> 00:34:40,989
And people come to
listen to that talk who

850
00:34:40,989 --> 00:34:43,290
are interested in birds
but they're not engineers.

851
00:34:43,290 --> 00:34:45,040
So when I do that
talk, I have to make it

852
00:34:45,040 --> 00:34:48,120
so somebody could understand
it who's intelligent

853
00:34:48,120 --> 00:34:49,889
but they're not
necessarily an engineer.

854
00:34:49,889 --> 00:34:51,530
So I give a different
kind of talk

855
00:34:51,530 --> 00:34:54,590
when I do that than when I
give an engineering talk.

856
00:34:54,590 --> 00:34:57,440
And I got invited
to a student dinner.

857
00:34:57,440 --> 00:35:00,960
I'm going out to somewhere
with some students on Friday.

858
00:35:00,960 --> 00:35:03,260
I'm going to give that how
I became a professor talk,

859
00:35:03,260 --> 00:35:06,020
and when I do the how I
became a professor talk,

860
00:35:06,020 --> 00:35:10,290
it's more general, and so it's
a different audience that I'm

861
00:35:10,290 --> 00:35:11,650
thinking about.

862
00:35:11,650 --> 00:35:14,152
And in some ways,
when I do these talks,

863
00:35:14,152 --> 00:35:15,610
it can be the same
group of people,

864
00:35:15,610 --> 00:35:17,600
but depending on what
I'm talking about,

865
00:35:17,600 --> 00:35:20,250
the way they look at
it is different, OK?

866
00:35:20,250 --> 00:35:22,600
So the market thing is
something to think about.

867
00:35:22,600 --> 00:35:25,530
So if you're writing
a thesis, your market

868
00:35:25,530 --> 00:35:28,560
is your PhD committee, who's
going to read the thesis

869
00:35:28,560 --> 00:35:30,020
and examine you on the thesis.

870
00:35:30,020 --> 00:35:31,827
If you're writing
a paper, you've

871
00:35:31,827 --> 00:35:33,410
got to think about
the market as being

872
00:35:33,410 --> 00:35:35,537
other people in your
research field, some of who

873
00:35:35,537 --> 00:35:37,620
are going to be the
reviewers, who are going to be

874
00:35:37,620 --> 00:35:39,890
reading it and criticizing it.

875
00:35:39,890 --> 00:35:44,020
If you're writing a general
popular science book,

876
00:35:44,020 --> 00:35:45,440
it's a different
kind of audience.

877
00:35:45,440 --> 00:35:49,600
If you're writing a
research proposal,

878
00:35:49,600 --> 00:35:51,964
the audience is going to
be the funding agency.

879
00:35:51,964 --> 00:35:54,380
Are they interested in what
you're talking about, but also

880
00:35:54,380 --> 00:35:56,700
reviewers, who are
going to be deciding

881
00:35:56,700 --> 00:35:58,800
whether or not to
give you the money

882
00:35:58,800 --> 00:36:00,836
and what the criticisms are.

883
00:36:00,836 --> 00:36:02,710
So you have to think
about who the market is.

884
00:36:02,710 --> 00:36:04,670
So that's one thing.

885
00:36:04,670 --> 00:36:08,164
And one thing that think about
in doing the writing-- you

886
00:36:08,164 --> 00:36:10,330
know Mike and I have written
several books together,

887
00:36:10,330 --> 00:36:12,329
and when I tell my neighbors
I've written books,

888
00:36:12,329 --> 00:36:14,350
they somehow think--
their first idea is

889
00:36:14,350 --> 00:36:16,265
that we start on
page one and we start

890
00:36:16,265 --> 00:36:17,890
writing the book from
page one and then

891
00:36:17,890 --> 00:36:20,176
we work our way
through to page 500.

892
00:36:20,176 --> 00:36:22,140
And that's not how
we do it at all

893
00:36:22,140 --> 00:36:24,134
and that's not how
I write papers.

894
00:36:24,134 --> 00:36:25,800
That's not how most
people write papers.

895
00:36:25,800 --> 00:36:29,060
You've got to think
about the big picture

896
00:36:29,060 --> 00:36:32,080
and think about,
roughly, what goes where.

897
00:36:32,080 --> 00:36:33,890
And then maybe
think about a draft

898
00:36:33,890 --> 00:36:37,190
that gets the
scientific facts right.

899
00:36:37,190 --> 00:36:40,690
You put the information
down, and then you

900
00:36:40,690 --> 00:36:44,180
try to figure out about how do
you make the style really nice?

901
00:36:44,180 --> 00:36:45,230
How to make it read well?

902
00:36:45,230 --> 00:36:47,444
How do you make it
easy to understand?

903
00:36:47,444 --> 00:36:49,610
How does one paragraph lead
into the next paragraph?

904
00:36:49,610 --> 00:36:51,070
So it's an iterative thing.

905
00:36:51,070 --> 00:36:53,660
It's not like you start
at page one or line one

906
00:36:53,660 --> 00:36:55,210
and you just start writing.

907
00:36:55,210 --> 00:36:58,710
So it's an iterative process,
the same as engineering design

908
00:36:58,710 --> 00:37:00,150
is an iterative process.

909
00:37:00,150 --> 00:37:04,340
If you were going to
design, I don't know,

910
00:37:04,340 --> 00:37:06,960
a skateboard or something,
you wouldn't just

911
00:37:06,960 --> 00:37:09,290
think you were going to make
one and that would be it.

912
00:37:09,290 --> 00:37:12,920
That's how writing is, and
often, students don't see it

913
00:37:12,920 --> 00:37:15,020
as this iterative thing.

914
00:37:15,020 --> 00:37:17,970
OK, so that's that page there.

915
00:37:17,970 --> 00:37:19,700
Let's see, I already
talked about market.

916
00:37:19,700 --> 00:37:22,590
I think I have another
little slide about-- here's

917
00:37:22,590 --> 00:37:24,880
another slide here
about markets.

918
00:37:24,880 --> 00:37:26,390
So this is what I just said.

919
00:37:26,390 --> 00:37:27,280
Who are the readers?

920
00:37:27,280 --> 00:37:28,535
How are they going to use it?

921
00:37:28,535 --> 00:37:30,660
So you've got to think
about who you're writing for

922
00:37:30,660 --> 00:37:36,240
or if you're giving a talk,
who's going to look at that.

923
00:37:36,240 --> 00:37:39,570
OK, now the next
phase is to make what

924
00:37:39,570 --> 00:37:42,370
Mike calls a concept sheet.

925
00:37:42,370 --> 00:37:45,230
I would just think of
this as an outline.

926
00:37:45,230 --> 00:37:47,620
And I always make
some sort of outline

927
00:37:47,620 --> 00:37:49,430
before I try to write anything.

928
00:37:49,430 --> 00:37:52,410
And there's different
ways you can do that.

929
00:37:52,410 --> 00:37:54,160
The thing that Mike's
got here and there's

930
00:37:54,160 --> 00:37:56,570
a nice little figure
on page six, which

931
00:37:56,570 --> 00:38:00,260
is what I've got up here, is
he takes a big piece of paper.

932
00:38:00,260 --> 00:38:02,930
In Europe, it would
be known as the A3.

933
00:38:02,930 --> 00:38:05,960
Here it would be known as
the eight and a half by 17.

934
00:38:05,960 --> 00:38:08,450
You take a big piece of paper.

935
00:38:08,450 --> 00:38:10,390
This stationery company
actually makes paper

936
00:38:10,390 --> 00:38:12,814
with big blank space in
the middle and little note

937
00:38:12,814 --> 00:38:15,230
space on the outside or you
could just use the back of it.

938
00:38:15,230 --> 00:38:17,150
So you take a big
piece of paper and you

939
00:38:17,150 --> 00:38:19,780
may think this is douffy,
but it actually helps.

940
00:38:19,780 --> 00:38:21,370
So you take your
big piece of paper,

941
00:38:21,370 --> 00:38:23,739
and you just make
boxes about each topic.

942
00:38:23,739 --> 00:38:25,280
You're going to have
an introduction,

943
00:38:25,280 --> 00:38:27,071
you're going to have
methods and materials,

944
00:38:27,071 --> 00:38:28,730
you're going to have
a result section.

945
00:38:28,730 --> 00:38:32,680
And you think about what should
go into each of those boxes.

946
00:38:32,680 --> 00:38:34,350
And what you're
trying to do here

947
00:38:34,350 --> 00:38:36,812
is think about the whole paper
and how it all fits together

948
00:38:36,812 --> 00:38:39,020
and what goes where and what
are you going to include

949
00:38:39,020 --> 00:38:40,890
and what are you not
going to include.

950
00:38:40,890 --> 00:38:43,380
So people think about writing
as sitting at the keyboard

951
00:38:43,380 --> 00:38:47,035
and typing, but
that's just the--

952
00:38:47,035 --> 00:38:48,660
how when you get a
problem on a problem

953
00:38:48,660 --> 00:38:51,610
set, you turn and crank, that's
the turning and cranking part.

954
00:38:51,610 --> 00:38:55,900
The thoughtful part is
figuring out what to put in,

955
00:38:55,900 --> 00:38:58,040
what to leave out,
what figures you want,

956
00:38:58,040 --> 00:38:59,490
how you organize
the whole thing,

957
00:38:59,490 --> 00:39:02,410
how you put it all together,
and this helps you do that.

958
00:39:02,410 --> 00:39:06,130
And you can make this--
it's just for you.

959
00:39:06,130 --> 00:39:07,950
It doesn't have to look great.

960
00:39:07,950 --> 00:39:09,450
You can make this
messy if you want.

961
00:39:09,450 --> 00:39:10,520
It doesn't really matter.

962
00:39:10,520 --> 00:39:14,079
But it's good to have some sort
of an overview of how you want

963
00:39:14,079 --> 00:39:15,620
to put the thing
together, and that's

964
00:39:15,620 --> 00:39:18,670
what this stage helps you do.

965
00:39:18,670 --> 00:39:21,630
So Mike's put other
little things here.

966
00:39:21,630 --> 00:39:24,910
So see papers by
so-and-so and so-and-so.

967
00:39:24,910 --> 00:39:26,216
So you've got an introduction.

968
00:39:26,216 --> 00:39:27,590
You want to talk
about something.

969
00:39:27,590 --> 00:39:29,780
You know there should be
some references go here.

970
00:39:29,780 --> 00:39:31,655
Maybe you think there's
some extra references

971
00:39:31,655 --> 00:39:33,237
you haven't got.

972
00:39:33,237 --> 00:39:34,820
Maybe something in
the method, there's

973
00:39:34,820 --> 00:39:36,686
some analogy you can use here.

974
00:39:36,686 --> 00:39:38,560
Maybe you need a figure,
needs a good figure.

975
00:39:38,560 --> 00:39:40,270
You don't have to
actually have the figure.

976
00:39:40,270 --> 00:39:42,728
You just say I need a figure
and you have a vague idea what

977
00:39:42,728 --> 00:39:44,500
the figure looks like.

978
00:39:44,500 --> 00:39:46,490
Here there's some
discussion point.

979
00:39:46,490 --> 00:39:50,230
Discuss this with collaborators,
Ed, all this stuff.

980
00:39:50,230 --> 00:39:53,890
So you just put down roughly
what needs to go where

981
00:39:53,890 --> 00:39:55,420
and you think about
the whole thing

982
00:39:55,420 --> 00:39:57,500
and how it's all
going to fit together.

983
00:39:57,500 --> 00:40:01,870
And then as you work through
it, it looks more like this.

984
00:40:01,870 --> 00:40:03,255
So this would be on page seven.

985
00:40:06,220 --> 00:40:09,940
And this is filled
in, and if fact,

986
00:40:09,940 --> 00:40:12,730
this particular one, what
he's written down here

987
00:40:12,730 --> 00:40:17,550
is the overview he made for
making this booklet, OK?

988
00:40:17,550 --> 00:40:19,700
So the things
refer to this book.

989
00:40:19,700 --> 00:40:21,454
So here's the introduction.

990
00:40:21,454 --> 00:40:23,620
Here's the little chart we
went through and through,

991
00:40:23,620 --> 00:40:26,470
the concept design, embodiment,
and detail, blah, blah, blah.

992
00:40:26,470 --> 00:40:27,900
Here's the need,
the market need.

993
00:40:27,900 --> 00:40:29,407
We just talked about that.

994
00:40:29,407 --> 00:40:31,990
Here's the concept thing that
we we're just talking about now.

995
00:40:31,990 --> 00:40:35,240
Then we're going to talk about
each of these different phases.

996
00:40:35,240 --> 00:40:39,550
And his initials are
MFA, Michael F. Ashby.

997
00:40:39,550 --> 00:40:41,580
Think out, that means
think about this more.

998
00:40:41,580 --> 00:40:43,040
I haven't figured this out yet.

999
00:40:43,040 --> 00:40:46,680
I need an example here,
all these kinds of things.

1000
00:40:46,680 --> 00:40:48,330
So this is the way he does it.

1001
00:40:48,330 --> 00:40:50,230
There's a couple of
other ways you can do it.

1002
00:40:50,230 --> 00:40:53,200
One way is to just make
a bullet outline, that's

1003
00:40:53,200 --> 00:40:54,294
typically what I do.

1004
00:40:54,294 --> 00:40:56,210
You know you're going
to have an introduction,

1005
00:40:56,210 --> 00:40:57,480
these different headings.

1006
00:40:57,480 --> 00:40:59,460
And you might put in
the bullet outline

1007
00:40:59,460 --> 00:41:02,180
these same sorts of things,
like I need this figure

1008
00:41:02,180 --> 00:41:04,560
or we need to get
one more set of data

1009
00:41:04,560 --> 00:41:06,800
or I need to look
up this reference.

1010
00:41:06,800 --> 00:41:08,990
So it doesn't have
to be finished,

1011
00:41:08,990 --> 00:41:11,510
but it's a thing that tells
you what have you got,

1012
00:41:11,510 --> 00:41:14,540
what do you need to do to
make it all come together.

1013
00:41:14,540 --> 00:41:16,570
So that's one way to do it.

1014
00:41:16,570 --> 00:41:18,680
Another way to do it is
by thinking about what

1015
00:41:18,680 --> 00:41:20,540
figures you want in the paper.

1016
00:41:20,540 --> 00:41:23,860
So some people, before
they write any words,

1017
00:41:23,860 --> 00:41:26,520
they say, well, I know I
want to have these figures,

1018
00:41:26,520 --> 00:41:29,060
and then they build the
words around the figures.

1019
00:41:29,060 --> 00:41:32,560
And they can even sketch
out what the figures are.

1020
00:41:32,560 --> 00:41:34,769
Some people even start before
they start the project,

1021
00:41:34,769 --> 00:41:36,185
they say what kind
of figures do I

1022
00:41:36,185 --> 00:41:37,480
want at the end of the project?

1023
00:41:37,480 --> 00:41:39,390
And they don't know if the data
is going to do this or that.

1024
00:41:39,390 --> 00:41:40,970
They don't know which way
the data is going to go,

1025
00:41:40,970 --> 00:41:42,920
but they say I want
to have a plot of one

1026
00:41:42,920 --> 00:41:44,525
thing versus another thing.

1027
00:41:44,525 --> 00:41:47,619
Oh, you're looking
like this is not OK?

1028
00:41:47,619 --> 00:41:48,160
AUDIENCE: No.

1029
00:41:48,160 --> 00:41:48,868
LORNA GIBSON: No?

1030
00:41:48,868 --> 00:41:51,550
OK, yeah, some people do this.

1031
00:41:51,550 --> 00:41:54,320
So even when you're
ready to write,

1032
00:41:54,320 --> 00:41:57,130
you could say to yourself,
well, in the methods,

1033
00:41:57,130 --> 00:42:00,380
do I need a figure that's a
schematic of some apparatus?

1034
00:42:00,380 --> 00:42:03,530
In the results, how am I
going to present the results

1035
00:42:03,530 --> 00:42:04,280
in the discussion?

1036
00:42:04,280 --> 00:42:05,920
Do we need some
other kind of figure?

1037
00:42:05,920 --> 00:42:07,890
So if you have a
set of figures, you

1038
00:42:07,890 --> 00:42:10,535
can work the text
around those figures.

1039
00:42:10,535 --> 00:42:12,960
So that's another
way to do this.

1040
00:42:12,960 --> 00:42:15,690
So those are just three
options, but all of them

1041
00:42:15,690 --> 00:42:19,140
have in common that you
think about the whole paper

1042
00:42:19,140 --> 00:42:20,690
and how it all fits
together and what

1043
00:42:20,690 --> 00:42:22,520
goes where and what
do you have already

1044
00:42:22,520 --> 00:42:25,400
and what else do
you need to get, OK?

1045
00:42:25,400 --> 00:42:27,230
So that's that.

1046
00:42:27,230 --> 00:42:29,170
And then what I
was going to do--

1047
00:42:29,170 --> 00:42:31,815
I think that's probably the
last figure that's-- yeah, OK.

1048
00:42:31,815 --> 00:42:33,440
So there's just this
little thing here.

1049
00:42:33,440 --> 00:42:35,481
So what I was going to do
is just talk about some

1050
00:42:35,481 --> 00:42:37,780
of the other things in
this little booklet that

1051
00:42:37,780 --> 00:42:42,780
work through each of these
stages of the writing.

1052
00:42:42,780 --> 00:42:45,437
So that's the concept,
and then the next phase

1053
00:42:45,437 --> 00:42:47,020
would be what's
called the embodiment,

1054
00:42:47,020 --> 00:42:49,350
if you think of the
design language,

1055
00:42:49,350 --> 00:42:51,090
and that would be
the first draft.

1056
00:42:51,090 --> 00:42:53,970
And I think most people find
the most difficult thing is

1057
00:42:53,970 --> 00:42:55,120
to write the first draft.

1058
00:42:55,120 --> 00:42:56,460
I mean, I find that the hardest.

1059
00:42:56,460 --> 00:42:58,300
Once you've got
something, editing it

1060
00:42:58,300 --> 00:43:00,270
is relatively straightforward.

1061
00:43:00,270 --> 00:43:02,230
You go, oh, this piece
should go over there

1062
00:43:02,230 --> 00:43:04,240
or there's something missing.

1063
00:43:04,240 --> 00:43:07,350
But getting the first draft
down is the hardest thing.

1064
00:43:07,350 --> 00:43:12,200
And one of the
things-- it's like when

1065
00:43:12,200 --> 00:43:14,590
I talked about
writing the book, you

1066
00:43:14,590 --> 00:43:16,730
don't write the draft
sequentially either.

1067
00:43:16,730 --> 00:43:19,020
I typically tell students
to start with the materials

1068
00:43:19,020 --> 00:43:21,145
and methods because that's
the most straightforward

1069
00:43:21,145 --> 00:43:22,874
and it's the easiest to write.

1070
00:43:22,874 --> 00:43:25,290
There's not a whole lot of
mystery to how you actually did

1071
00:43:25,290 --> 00:43:26,770
something you've already done.

1072
00:43:26,770 --> 00:43:29,310
So I tell people don't write
the introduction first.

1073
00:43:29,310 --> 00:43:32,300
That's a bad idea because
it's actually often not

1074
00:43:32,300 --> 00:43:33,930
so easy to write
the introduction.

1075
00:43:33,930 --> 00:43:36,970
So I tell people to write the
materials and methods first.

1076
00:43:36,970 --> 00:43:40,230
Write the result section
because you've got your results

1077
00:43:40,230 --> 00:43:42,390
and you know what the
results are going to be.

1078
00:43:42,390 --> 00:43:43,960
So those are the
two easiest things.

1079
00:43:43,960 --> 00:43:46,570
And often, I think,
what people find

1080
00:43:46,570 --> 00:43:49,755
is if they find it hard to write
it's because they don't know

1081
00:43:49,755 --> 00:43:52,380
what they want to write or they
haven't thought things through.

1082
00:43:52,380 --> 00:43:54,270
They haven't got their
thoughts together.

1083
00:43:54,270 --> 00:43:56,350
And if you've got
your thoughts, if you

1084
00:43:56,350 --> 00:44:01,490
know what you want to say, then
the writing becomes easier.

1085
00:44:01,490 --> 00:44:03,740
So one of the pieces
of advice Mike

1086
00:44:03,740 --> 00:44:06,890
gave me, and it's
in this booklet too,

1087
00:44:06,890 --> 00:44:09,580
is in the first draft
what you should try to do

1088
00:44:09,580 --> 00:44:11,240
is just get the facts down.

1089
00:44:11,240 --> 00:44:13,180
Just get the information
down and don't

1090
00:44:13,180 --> 00:44:14,994
worry about if it
doesn't sound quite right

1091
00:44:14,994 --> 00:44:17,160
or if this sentence doesn't
lead into that sentence.

1092
00:44:17,160 --> 00:44:19,230
Don't worry about the
style of it at all.

1093
00:44:19,230 --> 00:44:20,710
Just try to get the facts down.

1094
00:44:20,710 --> 00:44:22,430
Just try to get the
information down.

1095
00:44:22,430 --> 00:44:24,290
And once you've
got the information

1096
00:44:24,290 --> 00:44:27,120
and you've got some kind
of framework-- I'm not

1097
00:44:27,120 --> 00:44:30,000
saying that you don't want
to make the style good,

1098
00:44:30,000 --> 00:44:32,940
you do, but you don't need
to do that the first thing.

1099
00:44:32,940 --> 00:44:35,190
The first thing is just
to get the facts down,

1100
00:44:35,190 --> 00:44:38,080
and then you can
edit it later on.

1101
00:44:38,080 --> 00:44:40,830
It's more of this
iterative process.

1102
00:44:40,830 --> 00:44:43,000
OK, so the first draft,
the most important thing

1103
00:44:43,000 --> 00:44:44,482
is just to get the facts down.

1104
00:44:44,482 --> 00:44:46,440
Then, I'm not going to
read all of these things

1105
00:44:46,440 --> 00:44:49,400
because you can just
read them yourself,

1106
00:44:49,400 --> 00:44:51,219
but I'll just comment
on a few things.

1107
00:44:51,219 --> 00:44:53,135
So one thing he's got--
I'm on page eight now,

1108
00:44:53,135 --> 00:44:55,930
is the abstract.

1109
00:44:55,930 --> 00:44:57,790
So the abstract
should be concise.

1110
00:44:57,790 --> 00:45:01,521
It should be fairly
short and you

1111
00:45:01,521 --> 00:45:03,520
want to tell people why
you're doing what you're

1112
00:45:03,520 --> 00:45:06,400
doing, what you did,
what the key result is,

1113
00:45:06,400 --> 00:45:07,710
and what the conclusions are.

1114
00:45:07,710 --> 00:45:10,950
So it can be pretty short.

1115
00:45:10,950 --> 00:45:12,760
There's a section
on the introduction.

1116
00:45:12,760 --> 00:45:14,316
You can just read that.

1117
00:45:14,316 --> 00:45:15,810
Let's see here.

1118
00:45:15,810 --> 00:45:18,450
Yeah, I think, you can read
yourself these other things.

1119
00:45:18,450 --> 00:45:20,241
I don't want to go
through the whole thing.

1120
00:45:22,860 --> 00:45:24,980
All right, so that's that.

1121
00:45:24,980 --> 00:45:28,610
OK, so you get to the
end of the first draft,

1122
00:45:28,610 --> 00:45:30,710
there's a little
section on figures here.

1123
00:45:30,710 --> 00:45:32,835
Let me just make some
comments on that.

1124
00:45:35,570 --> 00:45:37,530
People who are busy
and may not want

1125
00:45:37,530 --> 00:45:39,610
to read every word
that you've written

1126
00:45:39,610 --> 00:45:42,160
will look at the figures, and
they'll look at the figures

1127
00:45:42,160 --> 00:45:44,244
to make some judgment about
does this look useful?

1128
00:45:44,244 --> 00:45:45,910
Does this look like
you've got something

1129
00:45:45,910 --> 00:45:47,260
I want to spend more time on?

1130
00:45:47,260 --> 00:45:52,040
So it's important to make the
figures easily understandable

1131
00:45:52,040 --> 00:45:55,130
and to be fairly self-contained.

1132
00:45:55,130 --> 00:45:57,989
So you want to make
the figures clear.

1133
00:45:57,989 --> 00:46:00,030
You don't want to have
too much information on it

1134
00:46:00,030 --> 00:46:02,211
so that people can't
follow what's going on,

1135
00:46:02,211 --> 00:46:03,960
and you want them to
illustrate the points

1136
00:46:03,960 --> 00:46:05,680
that you're trying to make.

1137
00:46:05,680 --> 00:46:08,120
So the figures are
very important.

1138
00:46:08,120 --> 00:46:11,140
And then when you've got
the first draft finished,

1139
00:46:11,140 --> 00:46:15,000
the next step, which I
find tremendously useful

1140
00:46:15,000 --> 00:46:18,210
and students often don't
get that this is a step.

1141
00:46:18,210 --> 00:46:19,760
The next step is
you put it somewhere

1142
00:46:19,760 --> 00:46:22,099
and you don't do anything
with it for a while.

1143
00:46:22,099 --> 00:46:24,140
And this is why it's
important not to write it up

1144
00:46:24,140 --> 00:46:25,640
at the last second.

1145
00:46:25,640 --> 00:46:29,250
Because there's something
about, you work on something,

1146
00:46:29,250 --> 00:46:31,300
you put it to one
side, you don't do it.

1147
00:46:31,300 --> 00:46:33,285
You just leave it and
you go do something else.

1148
00:46:33,285 --> 00:46:35,410
And then when you come back
to it, all of a sudden,

1149
00:46:35,410 --> 00:46:38,830
you see things that you didn't
see the first time through.

1150
00:46:38,830 --> 00:46:40,940
So the next step is you
just put it to one side

1151
00:46:40,940 --> 00:46:42,100
for a couple days.

1152
00:46:42,100 --> 00:46:44,070
But you can only do
that step for a class

1153
00:46:44,070 --> 00:46:47,534
if you started before the
night before it's due, OK?

1154
00:46:47,534 --> 00:46:49,200
So that's why you
have to start earlier.

1155
00:46:49,200 --> 00:46:52,530
That's why I'm telling
you this now, OK?

1156
00:46:52,530 --> 00:46:54,960
So you put it aside and then
you go have a cup of coffee.

1157
00:46:54,960 --> 00:46:56,543
You see there's
several cups of coffee

1158
00:46:56,543 --> 00:46:59,180
that Mike has happily
drawn for us here.

1159
00:46:59,180 --> 00:47:01,270
OK, then the next
part of this is

1160
00:47:01,270 --> 00:47:03,300
all about grammar and
sentence structure.

1161
00:47:03,300 --> 00:47:04,550
I'm not going to go over that.

1162
00:47:04,550 --> 00:47:05,999
You can read all that yourself.

1163
00:47:05,999 --> 00:47:08,040
But there is one amusing
thing I want to tell you

1164
00:47:08,040 --> 00:47:09,690
because there's a cute story.

1165
00:47:09,690 --> 00:47:10,940
I'm on page 16 now.

1166
00:47:10,940 --> 00:47:12,750
There's a thing about spelling.

1167
00:47:12,750 --> 00:47:14,610
Mike is a terrible speller.

1168
00:47:14,610 --> 00:47:16,470
When I was his student,
he used to-- there

1169
00:47:16,470 --> 00:47:18,030
were no word processors.

1170
00:47:18,030 --> 00:47:21,159
And we used to write things
and he would write things

1171
00:47:21,159 --> 00:47:22,950
and I would say, I
can't read your writing.

1172
00:47:22,950 --> 00:47:25,116
And he says, ah, well, I
make up for my bad spelling

1173
00:47:25,116 --> 00:47:27,120
with my bad writing.

1174
00:47:27,120 --> 00:47:29,400
So I couldn't tell if he
had spelled something right.

1175
00:47:29,400 --> 00:47:32,500
The other thing we
found was that, we

1176
00:47:32,500 --> 00:47:34,600
wrote the cellular solid
book, the first edition

1177
00:47:34,600 --> 00:47:36,700
was in the 1980s.

1178
00:47:36,700 --> 00:47:39,320
And I grew up in Canada,
then I lived in England,

1179
00:47:39,320 --> 00:47:40,450
then I moved here.

1180
00:47:40,450 --> 00:47:43,610
He grew up in Australia,
then he moved to England,

1181
00:47:43,610 --> 00:47:46,030
then he moved to the States
then he moved back to England.

1182
00:47:46,030 --> 00:47:49,050
And words that end, that
we spell I-Z-E, like

1183
00:47:49,050 --> 00:47:51,720
normalized, like
normalized variables.

1184
00:47:51,720 --> 00:47:55,730
They're I-Z-E here.

1185
00:47:55,730 --> 00:47:58,050
In England, they're all I-S-E.

1186
00:47:58,050 --> 00:48:00,710
OK, and then some of
the words, it turns out,

1187
00:48:00,710 --> 00:48:04,580
Canadians spell with an
I-Z-E and some with I-S-E.

1188
00:48:04,580 --> 00:48:06,990
So anyway, we wrote the
entire fricking book.

1189
00:48:06,990 --> 00:48:09,120
We were almost ready
to send it off,

1190
00:48:09,120 --> 00:48:11,850
and we have all those graphs
where the axes are normalized,

1191
00:48:11,850 --> 00:48:16,710
and we must have used the word
normalized like 100 times,

1192
00:48:16,710 --> 00:48:19,140
and we realized half the
time we had spelled it I-S-E

1193
00:48:19,140 --> 00:48:21,091
and half the time we
had spelled it I-Z-E.

1194
00:48:21,091 --> 00:48:23,590
And then we had to go back and
find them all and fix it all.

1195
00:48:23,590 --> 00:48:28,230
So anyway, that's just our
little story about spelling.

1196
00:48:28,230 --> 00:48:29,890
OK, there's a thing
about punctuation.

1197
00:48:29,890 --> 00:48:30,639
You can read that.

1198
00:48:30,639 --> 00:48:32,040
That's kind of boring.

1199
00:48:32,040 --> 00:48:34,350
I wanted to move on to
the bit about style,

1200
00:48:34,350 --> 00:48:37,480
because style is important too.

1201
00:48:37,480 --> 00:48:41,060
And people remember papers
that are well written.

1202
00:48:41,060 --> 00:48:45,450
Obviously, papers that have
valuable scientific information

1203
00:48:45,450 --> 00:48:48,150
are memorable too, but
if it's well-written,

1204
00:48:48,150 --> 00:48:52,020
it's more memorable, and the
style really is important.

1205
00:48:52,020 --> 00:48:54,330
And it's the same
with giving a talk.

1206
00:48:54,330 --> 00:48:56,670
You can convey the
same information,

1207
00:48:56,670 --> 00:49:01,160
but if you don't have it
presented in a clear way,

1208
00:49:01,160 --> 00:49:03,180
people aren't going
to remember it.

1209
00:49:03,180 --> 00:49:04,960
So the first rule--
so I'm on page 20.

1210
00:49:04,960 --> 00:49:07,360
The first rule,
now, is to be clear.

1211
00:49:07,360 --> 00:49:12,790
And being clear, it doesn't mean
having long-winded sentences

1212
00:49:12,790 --> 00:49:14,050
with lots of jargon.

1213
00:49:14,050 --> 00:49:17,710
It really just means make
it short, make it concise,

1214
00:49:17,710 --> 00:49:19,790
make it clear what
you want to say.

1215
00:49:19,790 --> 00:49:21,360
So Mike has several
examples here

1216
00:49:21,360 --> 00:49:23,680
of headlines from
the newspapers, which

1217
00:49:23,680 --> 00:49:24,840
were not clear.

1218
00:49:24,840 --> 00:49:27,310
So I'll just read these out
because I find them amusing.

1219
00:49:27,310 --> 00:49:29,580
"Red Tape Holds Up New Bridge."

1220
00:49:29,580 --> 00:49:32,630
So, OK, maybe the red tape
temporally held it up, but not

1221
00:49:32,630 --> 00:49:34,000
spatially held it up.

1222
00:49:34,000 --> 00:49:36,000
OK, and then here's another
one. "Something Went

1223
00:49:36,000 --> 00:49:37,950
Wrong in Jet Crash,
Expert Says."

1224
00:49:37,950 --> 00:49:41,420
In fact, you hear this all
the time on the news now.

1225
00:49:41,420 --> 00:49:42,900
Obviously, something went wrong.

1226
00:49:42,900 --> 00:49:45,233
You don't have to be an
engineer to figure out something

1227
00:49:45,233 --> 00:49:46,570
went wrong in a jet crash.

1228
00:49:46,570 --> 00:49:49,930
Then, "Chef Throws Heart In
To Help Feed the Hungry."

1229
00:49:49,930 --> 00:49:53,560
OK, well, maybe that's
a little too much.

1230
00:49:53,560 --> 00:49:56,480
This is my favorite one,
"Prostitutes Appeal to Pope."

1231
00:49:56,480 --> 00:49:58,385
OK, there's different
ways you can appeal.

1232
00:50:01,630 --> 00:50:04,420
You don't have to appeal
to the Pope in that way.

1233
00:50:04,420 --> 00:50:06,859
And then, "Panda Mating
Fails, Vet Takes Over."

1234
00:50:06,859 --> 00:50:09,150
I don't think the vet really
took over with the mating,

1235
00:50:09,150 --> 00:50:11,250
but you know what they mean.

1236
00:50:11,250 --> 00:50:15,480
OK, so one thing is clarity.

1237
00:50:15,480 --> 00:50:17,510
Another point is don't waffle.

1238
00:50:17,510 --> 00:50:20,640
You want things to be
concise and get to the point.

1239
00:50:20,640 --> 00:50:23,780
So he's got this
example here from what

1240
00:50:23,780 --> 00:50:27,490
he cites as a well-known but
anonymous materials text.

1241
00:50:27,490 --> 00:50:29,140
"The selection of
the proper material

1242
00:50:29,140 --> 00:50:30,960
is a key step in
the design process,

1243
00:50:30,960 --> 00:50:32,830
because it is the
crucial decision that

1244
00:50:32,830 --> 00:50:35,270
links computer
calculations and the lines

1245
00:50:35,270 --> 00:50:37,890
on an engineering drawing with
a real or working design."

1246
00:50:37,890 --> 00:50:39,414
But what does it say?

1247
00:50:39,414 --> 00:50:41,080
It says material
selection is important.

1248
00:50:41,080 --> 00:50:44,170
So don't say something
in some long-winded way

1249
00:50:44,170 --> 00:50:46,830
that you could say
in a short way.

1250
00:50:46,830 --> 00:50:48,290
OK, let's see.

1251
00:50:51,190 --> 00:50:53,450
So let me move on
to the next page.

1252
00:50:53,450 --> 00:50:55,900
The next step that I-- let
me emphasize one more time,

1253
00:50:55,900 --> 00:50:59,620
is 8.5, revise and rewrite.

1254
00:50:59,620 --> 00:51:02,934
So writing really is iterative.

1255
00:51:02,934 --> 00:51:05,350
Those books that you've seen
that Mike and I have written,

1256
00:51:05,350 --> 00:51:07,930
I cannot tell you how many
drafts of each chapter we went

1257
00:51:07,930 --> 00:51:09,800
through over and
over and over again.

1258
00:51:09,800 --> 00:51:16,080
So to make it good, you have
to do it over and over again.

1259
00:51:16,080 --> 00:51:17,850
OK, there's that.

1260
00:51:17,850 --> 00:51:18,350
Let me see.

1261
00:51:18,350 --> 00:51:20,650
Is there anything
else I have here?

1262
00:51:20,650 --> 00:51:23,020
Ah, here's a couple things
that are not so obvious.

1263
00:51:23,020 --> 00:51:25,850
So one is, for each
paragraph you should

1264
00:51:25,850 --> 00:51:27,870
have a good first sentence.

1265
00:51:27,870 --> 00:51:29,400
You should tell the
reader something

1266
00:51:29,400 --> 00:51:31,609
they don't already know.

1267
00:51:31,609 --> 00:51:34,150
So there's some examples here,
and you can read through them.

1268
00:51:34,150 --> 00:51:36,730
But it is really helpful
for each paragraph

1269
00:51:36,730 --> 00:51:39,580
to have a good opening sentence.

1270
00:51:39,580 --> 00:51:41,417
Another thing is at the
end of the paragraph

1271
00:51:41,417 --> 00:51:44,000
it's good if there's a sentence
that links it to the next one.

1272
00:51:44,000 --> 00:51:47,580
So it hints at what the next
paragraph's going to be about,

1273
00:51:47,580 --> 00:51:49,310
so it leads the
reader through it,

1274
00:51:49,310 --> 00:51:51,530
and it is a logical progression.

1275
00:51:51,530 --> 00:51:53,320
So an opening sentence
for the paragraph

1276
00:51:53,320 --> 00:51:55,500
and the final
sentence, you might

1277
00:51:55,500 --> 00:51:57,947
want to look at in a
bit more gory detail.

1278
00:51:57,947 --> 00:52:00,280
OK, and then there are some
references at the very back,

1279
00:52:00,280 --> 00:52:02,430
at page 25.

1280
00:52:02,430 --> 00:52:05,830
And I brought a couple of books
in that I have found helpful.

1281
00:52:05,830 --> 00:52:07,310
So you may have seen these.

1282
00:52:07,310 --> 00:52:10,260
One is called The
Elements of Style

1283
00:52:10,260 --> 00:52:13,540
and this is by Strunk and
White, so William Strunk, Jr.

1284
00:52:13,540 --> 00:52:14,760
and EB White.

1285
00:52:14,760 --> 00:52:18,630
You guys know EB White,
Charlotte's Web, same guy.

1286
00:52:18,630 --> 00:52:23,360
He's written this small, small,
not too long to have a look at

1287
00:52:23,360 --> 00:52:25,010
book about style.

1288
00:52:25,010 --> 00:52:30,610
So there's some rules of
usage, which is grammar stuff,

1289
00:52:30,610 --> 00:52:33,090
but there's principles
of composition

1290
00:52:33,090 --> 00:52:36,020
and there's a chapter called
"An Approach to Style."

1291
00:52:36,020 --> 00:52:37,820
And so here's some
of the headings.

1292
00:52:37,820 --> 00:52:39,630
Place yourself in
the background.

1293
00:52:39,630 --> 00:52:41,320
Write in a way that
comes naturally.

1294
00:52:41,320 --> 00:52:42,809
Work from a suitable design.

1295
00:52:42,809 --> 00:52:45,100
These people are not engineers,
but they're saying work

1296
00:52:45,100 --> 00:52:46,058
from a suitable design.

1297
00:52:46,058 --> 00:52:47,980
It's like that concept thing.

1298
00:52:47,980 --> 00:52:49,960
Revise and rewrite,
did I mention that,

1299
00:52:49,960 --> 00:52:51,130
revise and rewrite?

1300
00:52:51,130 --> 00:52:52,380
Do not overwrite.

1301
00:52:52,380 --> 00:52:54,950
Don't make it too complicated.

1302
00:52:54,950 --> 00:52:56,750
Avoid the use of qualifiers.

1303
00:52:56,750 --> 00:52:59,204
If you say something's very
stiff, what does that mean?

1304
00:52:59,204 --> 00:53:00,370
You can just say it's stiff.

1305
00:53:00,370 --> 00:53:02,670
You don't have to
say it's very stiff.

1306
00:53:02,670 --> 00:53:05,240
Very compared to what?

1307
00:53:05,240 --> 00:53:06,120
Let's see.

1308
00:53:06,120 --> 00:53:09,840
Use orthodox spelling, blah,
blah, blah, blah, blah.

1309
00:53:09,840 --> 00:53:12,130
Avoid fancy words.

1310
00:53:12,130 --> 00:53:14,630
OK, be clear, all
this kind of stuff.

1311
00:53:14,630 --> 00:53:18,170
So Strunk and White
is old but good.

1312
00:53:18,170 --> 00:53:21,450
And then, there's this
book here by Bill Bryson.

1313
00:53:21,450 --> 00:53:24,160
Bryson's Dictionary
of Troublesome Words.

1314
00:53:24,160 --> 00:53:26,490
So this is, it is
like a dictionary.

1315
00:53:26,490 --> 00:53:30,250
It goes by letter and
has different words,

1316
00:53:30,250 --> 00:53:32,430
but it talks about
how people sometimes

1317
00:53:32,430 --> 00:53:35,000
use a word thinking it means
one thing when it doesn't, it

1318
00:53:35,000 --> 00:53:36,590
actually means something else.

1319
00:53:36,590 --> 00:53:40,880
And so it's just words
that people use commonly

1320
00:53:40,880 --> 00:53:45,470
that they sometimes confuse
with what they really mean.

1321
00:53:45,470 --> 00:53:47,820
So it's a very handy thing too.

1322
00:53:47,820 --> 00:53:49,210
Do you know Bill Bryson?

1323
00:53:49,210 --> 00:53:50,821
Very funny travel writer.

1324
00:53:50,821 --> 00:53:53,070
If you ever go somewhere
that Bill Bryson has been you

1325
00:53:53,070 --> 00:53:55,420
should get the book he's
written about it because he's

1326
00:53:55,420 --> 00:53:56,830
very funny.

1327
00:53:56,830 --> 00:53:58,145
OK, so I think that's it.

1328
00:53:58,145 --> 00:54:00,270
Oh, and then, I think, the
very end of this booklet

1329
00:54:00,270 --> 00:54:04,330
has some examples of good
writing and bad writing.

1330
00:54:04,330 --> 00:54:07,510
So you can have a
look at that too.

1331
00:54:07,510 --> 00:54:11,757
All right, so are we good
on how to write a paper?

1332
00:54:11,757 --> 00:54:13,340
Do you have questions
on how to write?

1333
00:54:13,340 --> 00:54:15,670
Writing is important.

1334
00:54:15,670 --> 00:54:17,480
So I have one more
writing story.

1335
00:54:17,480 --> 00:54:20,530
So when I first got this job at
MIT, I was living in Arlington,

1336
00:54:20,530 --> 00:54:22,980
and my mom comes to
visit me from Toronto.

1337
00:54:22,980 --> 00:54:25,900
And I'm work, work, work,
work, working, working,

1338
00:54:25,900 --> 00:54:28,371
and my mom says to
me, she says, my, you

1339
00:54:28,371 --> 00:54:29,745
spend a lot of
your life writing.

1340
00:54:29,745 --> 00:54:32,040
I'm like, Mom, that's
what I get paid to do.

1341
00:54:32,040 --> 00:54:34,640
I get paid to write.

1342
00:54:34,640 --> 00:54:36,140
Like she always
thought I was should

1343
00:54:36,140 --> 00:54:37,600
be spending maybe
30 hours a week

1344
00:54:37,600 --> 00:54:38,980
lecturing or
something like that.

1345
00:54:38,980 --> 00:54:40,355
Like she, well,
you're a teacher.

1346
00:54:40,355 --> 00:54:42,810
You only teach three hours
a week, what is this?

1347
00:54:42,810 --> 00:54:43,930
I'm like, I write, Mom.

1348
00:54:43,930 --> 00:54:45,500
That's what I do.

1349
00:54:45,500 --> 00:54:48,700
So anyways, so
writing is important

1350
00:54:48,700 --> 00:54:51,110
and giving presentations
is important.

1351
00:54:51,110 --> 00:54:52,610
And no matter what
you end up doing,

1352
00:54:52,610 --> 00:54:54,490
you're going to end up having
to do those two things.

1353
00:54:54,490 --> 00:54:57,050
And if you do it well, it's
going to make your life better,

1354
00:54:57,050 --> 00:54:59,910
and if you do it badly, you're
not going to be so good.

1355
00:54:59,910 --> 00:55:01,860
So that's my message.

1356
00:55:01,860 --> 00:55:03,650
So I'm going to
stop there because I

1357
00:55:03,650 --> 00:55:05,470
haven't got the
next lecture ready,

1358
00:55:05,470 --> 00:55:07,710
and I can start that on Monday.

1359
00:55:07,710 --> 00:55:10,425
So Monday we'll do the
cell mechanic stuff.

1360
00:55:10,425 --> 00:55:12,800
And then let me just-- because
we're getting ridiculously

1361
00:55:12,800 --> 00:55:13,841
close to the end of term.

1362
00:55:13,841 --> 00:55:16,700
Like four weeks from
today is the last test.

1363
00:55:16,700 --> 00:55:19,320
I know, it's shocking.

1364
00:55:19,320 --> 00:55:21,795
So there's one lecture
on cell mechanics,

1365
00:55:21,795 --> 00:55:23,920
and then there's some more
engineering applications

1366
00:55:23,920 --> 00:55:24,480
of foam.

1367
00:55:24,480 --> 00:55:27,150
I'm going to talk about energy
absorption in foams and foams

1368
00:55:27,150 --> 00:55:29,000
in sandwich panels,
that kind of stuff.

1369
00:55:29,000 --> 00:55:30,990
And then, we're going to talk
about some natural materials

1370
00:55:30,990 --> 00:55:31,489
again.

1371
00:55:31,489 --> 00:55:33,880
We're going to talk about
natural structures, so

1372
00:55:33,880 --> 00:55:39,080
like natural sandwich panels
and natural cylindrical shells

1373
00:55:39,080 --> 00:55:40,465
with foamy cores.

1374
00:55:40,465 --> 00:55:41,840
So I've got lots
of nature things

1375
00:55:41,840 --> 00:55:43,490
at the last part of the
course, and you know

1376
00:55:43,490 --> 00:55:44,781
how I like those nature things.

1377
00:55:44,781 --> 00:55:46,970
So there you have it.

1378
00:55:46,970 --> 00:55:50,504
Bob's your uncle, as
my mother would say.

1379
00:55:50,504 --> 00:55:51,920
You know what Bob's
your uncle is?

1380
00:55:51,920 --> 00:55:53,669
Bob's your uncle is
an English expression.

1381
00:55:53,669 --> 00:55:56,020
It just means there you have it.

1382
00:55:56,020 --> 00:55:57,870
There you have it.