We Hold A 3D Bioprinting Breakthrough In Our Hands
every day
most of us used to be some piece of
technology that could be key
to treating and curing disease
developing new drugs
and maybe saving a lot of lives
you might carry it around with you in
your backpack or a handbag
might be in your car you might keep it
on your desk at work
now it’s not a computer it’s not your
smartphone
it’s hand sanitizer
now you might be thinking about how in
the late 1800s
when physicians started sanitizing their
hands with antiseptics between treating
patients
mortality rates in hospitals plummeted
that’s not what i have in mind hand
sanitizer is not going to transform
global health in that capacity any
further
so why do i say hand sanitizer could
lead to breakthroughs in medicine
and maybe save a lot of lives
it’s because hand sanitizer has inspired
the development of a new
3d bio printing technology that gives
researchers practically unlimited
freedom
to perform experiments in ways that are
otherwise impossible
i believe this new freedom will unleash
the creativity and productivity of
researchers
as they develop and test new therapies
and study the the fundamentals of tissue
malfunction
now if you don’t know much about 3d
bioprinting or 3d printing more
generally think of it like this
to create a 3d structure of my own
design i need to take
a liquid and push it through a
translating nozzle
and that liquid has to stay right where
i put it until
it turns into a solid and by laying down
layer after layer
of liquid that rapidly turns into solid
i build up a 3d structure
this simple picture captures most of 3d
printing out there
where the liquid that turns into a solid
is just melted plastic that rapidly
cools and solidifies
so it’s 3d bio printing i mean you can’t
just
melt living tissue push it through a
nozzle
well 3d bioprinting the liquid i push
through the nozzle is a mixture of
living cells
and all the materials they need to live
and the problem
is that this liquid doesn’t rapidly
solidify and hold its shape like melted
plastic
and this is where hand sanitizer comes
in
to understand how hand sanitizer solves
this problem
let’s think about what makes hand
sanitizer unique
imagine walking down the aisles of the
grocery store the pharmacy
and seeing all the personal care
products lining the shelves
shampoo conditioner lotion body wash
liquid soap and hand sanitizer
what’s different about how hand
sanitizer looks
if you haven’t thought of it yet the
answer i’m looking for is bubbles
you never see bubbles trapped in bottles
of all those other
products but you always see bubbles
trapped in bottles of hand sanitizer
those bubbles teach us that hand
sanitizer has unique physical properties
that those other products lack those
bubbles are the key
to turning hand sanitizer into a tool
for biomedical research
now there’s an entire field of physics
devoted to studying materials like hand
sanitizer
formally it’s called soft matter physics
those of us in the field sometimes call
it squishy physics
and in the world of squishy physics
decades of research and debate
has gone into understanding materials
like hand sanitizer
we asked simple questions like are they
solids are they slowly flowing fluids
maybe they’re really soft glasses and
what gives them their properties
it’s answers to questions like these
that teach us why we always see bubbles
trapped in bottles of hand sanitizer
but never in those other soft squishy
materials
in all solids liquids
and the soft squishy stuff in between
buoyancy forces dried
bubbles up you know this bubbles rise in
water
bubbles even rise in really viscous
fluids like molasses
and i hope this picture of molasses here
reminds you you never see bubbles
trapped in jars of molasses
so if bubbles rise in water and molasses
but they don’t rise in hand sanitizer
the hand sanitizer itself
must be resisting the force holding the
bubble still
materials that can resist forces while
sitting still are solids
think about it you push on a fluid it
flows you push on a solid
it deflects or bends a little bit
but it comes to rest and resists the
force
sitting still bubbles
in hand sanitizer are at rest sitting
still
resisted by the hand sanitizer hand
sanitizer must be a solid
but i can pour hand sanitizer i can pump
it up through a nozzle i can smear it
all over my hands
that seems like a fluid well that’s
right
hand sanitizer is a fluid when it’s
flowing
both perspectives are correct hand
sanitizer is a solid when sitting still
and a fluid when flowing
now to understand how that works and to
convince yourself it’s true let’s think
of another material that’s a solid when
sitting still in the fluid when flowing
it’s the ball pit kids play in when kids
lay still in a ball pit
the ball pit can support their weight
acting like a solid
but when kids start stroking the arms
and kicking their legs
they can literally swim when flowing
they act the
the ball pit acts like a fluid
hand sanitizer is just a microscopic
version of that ball pit
in fact hand sanitizer is made from tiny
little microscopic balls all packed
together
the only difference is those little
balls are soft and squishy and swell up
in water-based liquids
so now you know how hand sanitizer works
how do we turn it into a tool for
biomedical research
well here’s the idea if i can randomly
disperse bubbles throughout a bottle of
hand sanitizer
what if i place them at carefully chosen
locations in 3d space to create a
structure
i’d be 3d printing with air
and if i can randomly place kids
anywhere in a ball pit
what if i place those kids at carefully
chosen locations in 3d space to create a
structure
i’d be 3d printing with kids
if i can 3d print with air into hand
sanitizer or kids with a ball pit
why can’t i do the same thing with
living cells i just have to develop a
material
that has the physical properties of hand
sanitizer but all the chemical
properties of the liquids we typically
grow cells in
so that’s what we did for the past five
years my lab at the university of
florida has been developing
a cell culture medium that has the
physical properties of hand sanitizer
here you can see what it looks like to
3d print into this material
we can create 3d structures of high
complexity
out of nothing but liquid trapped in
space just like bubbles in the hand
sanitizer
just like kids in the ball pit with this
method
we can 3d print precise complex
structures out of living cells
just look at these tiny matryoshka dolls
nested inside one another
the smallest one is about the size of a
grain of rice
now with these tools we’ve conducted a
lot of different investigations
here you see microscopic examples of our
3d printing method at work
we’ve developed tiny models of the human
liver to test compounds for toxicity
we studied how precisely fabricated
cellular structures evolve and shape
under the forces cells generate
we’ve created models of developing
tissue hoping one day to use our tools
to understand critical aspects of
embryonic development in one of our
investigations
we 3d printed model brain tumors
surrounded by
immune cells the idea was inspired by
our colleagues in the department of
neurosurgery
doctors catherine flores and dwayne
mitchell a few years ago
they developed a new type of
immunotherapy effective against brain
tumors
they were targeting a type of brain
cancer called glioblastoma
now some cancers aren’t susceptible to
the revolutionary new immunotherapies
that have been
developed recently and glioblastoma is
one of them
by infecting mice with glioblastoma and
testing hypothesis after hypothesis
they eventually came up with an
effective immunotherapeutic strategy
the process took years now imagine
if they could have placed the cells
anywhere they wanted in the mouse and
seen directly into the mouse’s brain at
high magnification
and watch precisely as the immune cells
attacked the tumor
and rapidly rapidly tested their
hypotheses and harvested the cells
whenever they wanted to for biochemical
testing
in other words imagine if they could do
experiments that replicate what happens
in the mouse
without all the restrictions of working
with mice
their discovery could have been made in
a matter of weeks or months not years
teaming up with them our labs proved
that this fantasy may soon be reality
my phd student cameron morley 3d printed
hundreds of glioblastoma
glioblastoma tumor models surrounded by
immune cells
varying things like their proximity to
the tumor and
testing all of the necessary controls
and replicates
he performed time-lapse imaging on a
microscope
at high resolution watching in detail
how the
immune cells attack the tumor with a
level of precision you just can’t get
when working with a mouse
to test whether the cells in our hand
sanitizer material behave the way they
do in a mouse
cameron used our printer to harvest the
cells
you can see that by embedding cells in a
material like hand sanitizer
we’re able to uh suck suck
the immune cells out and harvest the
tumors in fact
this process is a lot like pumping
material up through a
hand sanitizer uh dispenser except in
our case
the needle the the dispenser tube is a
fine needle about as narrow as a human
hair
precisely positioned by a 3d printer
sitting on top of a microscope we’re
able to
move this needle around sucking out all
the immune cells
and then come back and suck out the
tumor
cameron harvested the cells from his
hundreds of different experiments
handed them off to catherine flores lab
for biochemical analysis
and based on their gene expression
profiles we found that
cells in the hands sanitizer material
indeed behave the way they do in the
mouse
now this first investigation of
glioblastoma was a critical first step
to convincing the world and convincing
ourselves that this crazy idea of
turning hand sanitizer into a tool for
biomedical research
would enable us to perform experiments
that reproduce what happens in living
tissue
but without all the restrictions of
working with real live animals
we hope with enough examples like these
we can convince the whole world
to use our technology now most the
biomedical research world out there
recognizes the critical importance of
studying cells in 3d contexts
it’s the first step toward mimicking the
body
but they also realize that it’s usually
not worth the time effort and expense
to create 3d structures out of living
cells it’s really hard to do
i think what i think we’ve made it a lot
easier to do
taking inspiration from the bubbles and
hand sanitizer
developing new 3d bio printing
technology combined with a 3d culture
medium
today we’re 3d printing the experiments
we imagine
rapidly testing our hypotheses and soon
i hope
accelerating the pace of life-saving
discoveries and biomedical research