OK My name is Bob Goldberg.

I'm from the Woodruff school of mechanical
engineering in my laboratories in

the petite Institute for Bioengineering in
bio science and I'm happy today to give

an overview of some of the research going
on in my laboratory which I've titled

The degeneration and
regeneration of muscular skeletal tissues.

So diseases and injuries to muscular
skeletal tissues collectively represent

the most common cause of severe long term
pain and physical disability worldwide.

The cost to our society in the US alone
is over two hundred billion dollars and

therefore with that motivation in mind the
overall goal of the work in my laboratory

is to better understand the mechanisms
of tissue degeneration as well

as establish new regenerative strategies
that will advance their appeals for

a wide range of high priority
clinical problems including for

example last year pro says related to
bone osteoarthritis related to cartilage

degeneration growth plate and
development disorders as well as

composite injuries to bone vasculature and
nerves associated with severe limb trauma.

To meet this goal we have developed and
utilize a wide range of

enabling technologies including by
a mechanical modeling techniques.

As you can see here looking at the
initiation of micro damage in bone as we

age and the associated local stresses that
are responsible for that micro damage.

A variety of different bio materials
including in a fiber mesh is and

three dimensional scaffolds protein
delivery systems stem cells from different

sources as shown here stem cells from bone
marrow migrating on nano fiber meshes.

We use preclinical testing models
to evaluate these different

enabling technologies in their piece
before taking them into the clinic and

a variety of different.

Techniques to use as outcome measures.

Perhaps our favorite enabling technology
is micro computer tomography imaging or

micro C.T. imaging.

This X. ray based imaging technique is
a highly efficient three dimensional

quantitative imaging technique that gives
you analyses of not only tissue morphology

but also the composition of the tissues
the resolution is down to the micron level

and as you can see here you can do in
vivo launched two nil scanning over time.

This is in fact the standard technique
that's used for looking at changes in

the microstructure of bone associated with
aging as well as diseases such as ask your

proceeds over the last ten years we've
taken the advantages of this technique and

begun to apply them in tissue engineering
and regenerative medicine for looking at

three dimensional scaffold biomaterials as
well as looking at bone regeneration and

then most recently we've further extended
the use of this technique by adding

in contrast agents that allow us to not
only look at mineralized tissues but

also begin to look at non mineralized
issues such as cartilage and

bone and cartilage and blood vessels.

So just to give you one example of
that this is a rabbit distal femur

which if we scan in a micro C.T. system we
get an image of the mineralized tissue but

we don't see any of the cartilage
on the surface of the joint but

by a quill abrading this joint in contrast
agent we can now see the articular surface

including for example scalpel marks
that were made in the surface of

the joint as well as the insertion points
for the ligaments and most importantly we

can actually separate the bone in the
cartilage and analyze these in a segmented

fashion so that we can look at
changes in the surface of this joint.

So for example this is the articular
surface of the cartilage

that we have analyzed and
we've looked at the morphology and

in particular the thickness
of the of the cartilage.

And mapped out across the surface
of the joint surface.

So we're using this for a variety of
different purposes one of them is to look

at the progression and
treatment of osteoarthritis.

This is a model we've developed in rats in
which we inject Monosodium I doto acetate

which induces very rapid
degeneration of the joint and so

we would inject this chemical at time
zero and then use this contrast based

imaging technique to look at the changes
in the joint different time points.

Here you can see just one
example three weeks out

after injection where
the degradation of the cartilage

has proceeded down to the surface
of the to regular bone.

And we can use this technique now
not only to better understand

us are worth rightists but
also then to look

at different therapies that are being
developed to treat osteoarthritis.

And some of the companies
that we work with.

In the Institute for Bioengineering
bio science are now using this to

technique to test some of their
last two or three years therapies.

Now to move on to give you another example
related to our regenerative medicine work.

This is a model we've developed in
rats to look at large bone defects.

This is a large bone defect in the rat in
which we use a plate to fix the defect and

are able to study different strategies
repair for repairing these very large and

challenging bone defects the plate model
that we use allows us to use in vivo

micro C.T. to to monitor
the progression of bone in growth

as well as to do by mechanical testing of
the functional restoration of the limb.

Here you can see that if we implant to
buy a material only into the defect and

this is a bomb material that was invented
at Georgia Tech that has logic to no

prosody to induce growth from one into the
other we get an increase in the bone in

growth but not what we are not able
to repair the function of the limb.

So.
That means we have to add some sort

of biological component and

there are different regenerative
strategies that can be employed one can

use three dimensional scaffolds to
provide a template for regeneration or

one could use what's called guided bone
regeneration in which there's essentially

a two dimensional membrane that's
provided on the outside of the defect and

the interior is filled with biologic
cues that help to restore the defect.

And this is one example of such
a study in which we've used

a membrane composed of a nano fiber
mesh either without perforations or

with perforations and
we are filling that nano fiber

mash with an algae gel that's delivering
a protein in a sustained manner.

So here you can see the release
of the protein over time and

we get a release of about seven to
ten days of this of this protein.

So the way this experiment would proceed
is we create the segmental defect.

We put on the nano fiber mesh guided
membrane and then sort of fill it like

a sausage with these regenerative cues and
you can see the surgical

picture with the implanted nano fiber
mesh and here are some of the results.

Comparing different groups of
four weeks the mesh alone.

There's no repair mesh.

Plus the hydrogen.

There's no repair but either the mesh
alone or the perforated mesh with algae

an Ambien P. you can begin to see some
bone from Asian even by four weeks and

by twelve weeks particularly in
the perforated Mashonaland B.M.P.

is very nice bridging of this defect.

Now that's a very qualitative result and
so we use micro C.T.

again as enabling technology again to
quantify this and you can see it for weeks

the perforated mashes are significantly
greater than any of the rest and B.M.P.

has a significant effect on the repair and
by twelve weeks.

Both of the B.N.P. groups have
completely bridge those defects.

Most importantly we have to look at
function and so if we test these now.

Now following the experiment to
look at how well we've been able

to restore the mechanical
strength of these long bones.

You can see that compared to the intact
controls group four which had

the perforated meshes and B.M.P. were not
significantly different from these intact

controls indicating that we've developed
a technology now that is able to restore

function to these very challenging defects
within just twelve weeks and this work now

has been patented and is being moved
on to testing in large animal models.

So to conclude in the end our job we
feel is to make an impact by Dennett

find some of the grand challenges and some
of our current work is being funded by

the military to look at severe limb trauma
coming back from soldiers from the war.

To death by these grand challenges and
then investigate fundamental fundamental

mechanisms that are required to overcome
some of the barriers to repair and

apply our different biomaterials and
imaging techniques

to enable the development and translation
of improved clinical options for

patients with muscular skeletal
injuries and diseases.

Finally I'd like to just show
the outstanding group post-docs graduate

students and
staff who currently work in the lab

as well as several that have
already graduated from the lab and

currently have jobs in academia
industry and the government.

Thank you.