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