so thank you very much Jessica so again
welcome to this taster session which is
on biomedical materials science
I am Dr Mohammed Hadis and the taster
session will essentially be delivered by
my colleague Dr Gowsh who's just
waving at you just there so once again
welcome to this taster session and I
hope you enjoyed the talk
so our biomaterials course is situated
within the School of Dentistry so the
home for the biomaterials school
biomaterials course is the Birmingham
Dental Hospital and School of Dentistry
and these are images of our fantastic
new building which we have been
occupying since 2016 and within this
building we have access to state-of-the-art
research facilities as well
as state-of-the-art clinical facilities
as well and teaching facilities and as
well as beautiful green landscapes
biomaterials are an integral part to
modern-day medicine we find biomaterials
in all applications ranging from contact
lenses which some of you might wear to
stents within the heart valve artificial
hip replacements as well as knee
replacements artificial
heart valves pacemakers implants as well
as bone graft substitute materials and
the talk or the taster session today
will essentially focus on bone graft
substitute materials which dr. Gowsh is an
expert in so with that I'd like to hand
you over to my colleague Dr Gowsh for
the remainder of the taster session
so good afternoon everyone and for those
of you coming back welcome back so
bone grafts bone is the second most
transplanted tissue and does anybody
know what's the first most transplanted
tissue any guess
could it be a liver liver transplant but
- but it's blood blood is actually a
tissue and it is transplant it's the
most transplanted tissue and so bone
forms the second most transplanted
tissue and so you can imagine comparing
to blood bone being second is a
significant amount of bone grafting
performed
on several different indications
indications can range from fracture
where you have non-union of the fracture
join so you do need bone graft
to then aid in bone formation
you might also get bone grafting to
fuse skeletal bone after a herniated
disc is removed then you might also have
bone grafting within dental extraction
sockets and if the bone has either died
or resorbed away after time and you want
to place an implant into that hole
dental implant into that hole then you
have to regrow that bone before you can
insert a dental implant and then also in
the maxillofacial area again and
children born with cleft palate and
malformity require surgical correction
and often they require bone grafting and
to get the shapes back into the
appropriate shape and so there's so
many of the procedures and orthopedics
that require bone grafting and so it's a
it's a major field and
a clinical indication so
globally bone graft substitute market
was two point four billion dollars in
2016 and it's expected to grow
significantly with increasing active
aging population so current gold
standard is autografts so autografts are
bone harvested from the patient
themselves so for oral bone grafting so
for example here the person's lost their
tooth and they need new bone grafted
into the defected site before they can
have an implant put in what would happen
is the surgeon will go and remove bone
plugs from somewhere else in the jaw
bone and then put it in and then wait
for a new bone to grow
and drill in a hold place implant and
then the crown can go on top of it so
whereas in other procedures requiring
bone grafting it's more common to take
bone from the iliac crest so this is the
waist the bone in your waist around your
waist and this bone is taken as
either a plug or mashed up ground plug
as well and which can then be inserted
into the defect that require new bone
formation so this leads to a second
surgery a new site of where you've
opened up and taking new bone out and so
you've disrupted the environment so this
leads to pain in mobility for the
patient and can also lead to infection
by that second surgery and so and
another problem with autografts is that
if you have a large defect that you want
to regenerate you're limited to the
amount of bone that you can take from
within the patient so you wouldn't be
able to regenerate a large defect and
you certainly wouldn't be able to do a
second surgery aiming to take bone from
the same site Gowsh is it possible to
take bone from other people like we've
all heard of organs being transplanted
from other people but is it possible to
also take bone from other people that's
a good question and yes bone is a
tissue and an organ so it's possible to
take bone from other people and as you
will know Mo if you're taking organs
from other people that organ has that
the biological match has to be very good
for it to be not to be rejected and
function in the right way and same with
bone if you're taking bone from other
people from other doners then the
biological match has to be appropriately
tested and so on because that's
difficult to do and so on so I don't
really know of cases where bone is taken
from
live people so for born grafting often
bone is taken from dead people so
cadavers and also animals as well so
like cow bone is taken quite a lot and
this once they take this bone they treat
it significantly to remove all the cells
and the proteins and other growth
factors that might be there which might
then lead to rejection or disease
transmission so when you do that you
essentially degrade the bone its
capacity to regenerate bone is lost
significantly because you removed all
the growth factors and all the cells
that are required so essentially you're
just implanting scaffold and that has a
shape or structure similar to bone
but not the growth factors and so on so
even with those there is the
possibility that you might transmit some
disease or so on so synthetic bone
grafts are preferred and so synthetic
bone grafts are man-made so they can be
made without any biological factors
and also with reproducible structure and
properties right so here you can see
ceramic synthetic grafts in porous
granules and then you can also have a
putty like synthetic graft so this is
binder mixed into these synthetic graft
to make it flow like play-doh and then
you can also get implants coated with
these ceramic grafts and this is
dental implants coated with these
ceramic crafts as well and can we get
the poll to play if that's possible
Jessie yeah so ten seconds to answer the
question what biomaterial is in a bone
graft substitute so some of these
bone graft substitutes I just explained
would anybody be able to
say what
Biomaterial is in this
great let's see what they came back
with so did anybody say glasses
Wow nobody said glasses so bioceramic
well done very good yeah hydroxyapatite
is a really popular one that's the same
mineral has a similar composition to
bone mineral so very appropriate to use
hydroxyapatite and crushed bone again
yeah very good because you get
bone from other people and animals
that be crushed up into granules and
implanted and nobody went for glasses
yeah good alright but here's the thing
bioactive glasses can be used for
regenerating bone as well and bioactive
glasses have been in use since 1990s and
they've been implanted in over to 2
million people for different bone
surgeries and they were invented by
someone called Larry Hench in the
sixties and they're very similar to
window glass but they degrade in the
body and they actually stimulate newborn
formation so glasses can also be used to
regenerate bone you sure about that
Gowsh
because I wouldn't be very comfortable with
having glass in my body or within my
bones yeah I mean I do you think it'll
have the required mechanical properties
and the biological properties well good
point Mo
I wouldn't put window glass in my body
either window glass will be rejected and
and will either cause infection or just
pop out as its pushed out by your own
body so anything that's foreign glasses
are foreign to you to you will be will
have a foreign body reaction and then
that will make sure that that
foreign body is either sealed away or if
it can be pushed out of your body slowly
so if you look at window glass window
glass is mostly silica so sand
so it's very stable when
it rains you don't have anything that's
degrading away or forming a coating on
it whereas bioglass is very special so
bioactive glasses have very have high
amounts of these network modifiers or
calcium and sodium ions that make the
silica the glass to break up so it's
broken up into very unorganized
amorphous structure which means that
when you put it into your body it
actually degrades and
degrades over time releasing ions which
are which lead to a stimulatory effect
and over time this graft is completely
degraded away and newborn forms in its
space so here's a quick video on how it
works
you
so while this video is playing so you
mentioned that bioglass is similar to
normal window glass but from what I
understand silicon normal sand blaster
is made out of sand is very stable and
we see this for example in the desert or
on the beach so why is it that bioactive
glasses are able to disappear from the
body whereas we don't see the same
effect in on the beach or in a desert
yeah that's a good question and I
briefly mentioned it before basically if
you look at window glass or the sand and
it is silica so silicon bonds it for the
silicon through oxygen so it forms a
tetrahedral unit and bonds it for other
oxygens so if you imagine if the
tetrahedral is completely bonded
to other silicons you form a really
dense network right so a dense network
is harder to break and and penetrate and
will be more stable so the sand in the
desert you would see is it's very highly
densely formed network right so it's
hard to break that up and it wouldn't
disappear for a long time right
whereas bioactive glasses again they are
formed of silica so you still have this
tetrahedral unit structure but out of
the four oxygen silicon bonds you can
form only two are actually bonded so
other two of the oxygens on the
tetrahedra are bonded to silica calcium
ions or sodium ions so calcium and
sodium ions actually break up this
silica network in the glass and makes it
highly soluble right so that's why it
degrades in the body right so over time
it will degrade away and then and then
you get new tissue forming and this
kind of shows that schematically
so remember I said something about
foreign body reaction again if you put
bioactive glasses in the body they are
foreign to you to yourselves and the
body environment so they will be
rejected however what happens when you
put bioactive glasses in the body is that
you get a courting with these
bioactive glasses with hydroxyapatite so
hydroxyapatite is similar to the bone
mineral in the bone right the
crystalline mineral face in your bone so
the body thinks it's actually part of
itself and so it doesn't mound the same
foreign body reaction it would do to
normal window glass instead it treats
bioactive glasses as part of it's own
system and starts to develop new bone
tissue on top of it
[Video plays]
[Video plays]
[Video plays]
but so there you saw that you know
you put in the bioactive glasses it
starts a reaction and forms a hydroxide
that surface which stops it from being
rejected and over time you get
osteoblasts which form new bone come on
on top of bioactive glasses and build
new bone and osteoclast come in and
resolve the new bone and remodel it
in the right appropriate structure and
properties however the main problem with
bioactive glasses is
because of the way they are made they
can only be made as powder or
granular structures so they're only
available commercially as powder or
granular form so one of the work that
we've been doing at the University of
Birmingham is to develop these bioactive
glasses in a 3D porous structure so
they can be packed into defects and
have a porosity within them so you
can get bone growing within the tissue
and then you can get blood vessels
growing in there as well so they can be
used to repair long bone defects and so
on so here's a process where we go from
a solution and we send bioactive glass
fibers that look like cotton wool right
and and this oh Gowsh this looks very
much like candy floss to me so in terms
of mechanical properties how do we
achieve mechanical properties with
something that is so soft and candy
floss like yeah you're right so Mo I
wouldn't put this into a load-bearing
site so if you had a tibial fracture you
wouldn't use this material to load it
instead this would be very useful in non
load-bearing sites so for example in the
tooth extraction defect this would be
ideal because you could just pack it in
there and allow bone to grow it and
surgeons actually like this
structure because they are familiar with
cotton wool and they feel that they can
easily pack it into complex defects
defects that are hard to get into with
powder and so on another benefit with
the cotton wool-like structure is that it
maintains a 3D environment and it
keeps at the integral it is integral so
it keeps a 3D shape rather than powders
which might come out into defect from
the defect site and so on so and another
benefit with this is that you know I've
had people dentists tell me that there's
their patients come back complaining
that granular materials when input into
periodontal disease sometimes seep out of
the wound and when they're eating they
start to bite into these granular
bioactive glass particles or
crushed up bone whereas having fibers
like this they would mold into shape and
and fit into that defect so there's
lots of benefits to using a
three-dimensional cotton wool-like
structure over granular materials and
this reminds me of a story once my
friend told me about having the feeling
of biking sand when he was after having
a periodontal disease treatment so I
guess it's something quite interesting
that they get the feeling of biting sand
from these kind of glass structures it's
true Mo like some people have
even said like glass granulars are so
sharp that surgeons sometimes are scared
to pack it in with their gloves because
they're scared that it might look less
open and cut it but a cotton-wool like
structure because the fibers are
nanometer in size that they they bend
and deform rather than crack and poke so
that adds a benefit to their structure
as well and so typically you know
something like this would be very easy
to pack into a 3D under a 3D printed
guided bone regeneration mesh into
a complex defect and give it six months
to regenerate new bone and then you
would then place your influence and your
crown on top of that so at the moment
you know we've gone through a material
development phase and we've done
lots of in vitro testing which shows it
as potential or even better than
traditional bioactive glasses and we've
also done small animal studies as well
where we've compared it to bioglass
which is a traditional bioactive glass and
we get similar bond formation in
small animals the next thing to do is to
look at a large animal that has similar
defect model to one that we would
target this material clinically for and
test its efficacy and safety there and
once it's passed the safety and
it proves to be more efficacious than
what's currently available we will then
go and do some clinical trials with
different stages of clinical trials and
then it would be available for people to
use on the NHS or in dentistry so how
long do you estimate that might be so
obviously getting it through all the
regulatory phases it might take a while
so how long in your opinion do you think
it might be a bit before we see this
available on clinics for doctors or
surgeons to use so the thing is you know
if you if you're developing materials
for like say for energy applications or
automotive applications something
that's developed from the lab all you
have to do is go through scope the
opportunity and show that you can
manufacture it and upscale it and then
then it's immediately available once you
do some safety testing for it to be used
in civilian purposes while for
biomedical materials materials like these
cotton wool-like fibers we have to go
through extensive testing because these
are going into people and if they aren't
tested first for their safety they
could be life-threatening and if not you
know you could lose limbs and lose
parts of your body
and then also because of the amount of
work and development that needs to go
into this they have to be better than
what's available out there and some
people they have to be at least 30%
better in terms of how fast it
regenerates bone or what quality it
regenerates bone to so there's extensive
testing for safety and then efficacy
before they're available for use in
clinic so they so for something like
this it could range from 3 years to 15
years of testing through different
phases of trials so it is a long
time before it would be available in
the clinic but however the rewards are
massive compared to you know a small
development in automotive industry or
energy industry because these will go in
and change the way clinicians treat
patients and bone defects and 
there's lots of potential to
functionalise these grafts with
antibiotics or antibacterial material so
it opens up treating people who are
suffering from bone bacterial
infections people suffering from like
oral and neck cancer can be treated with
things like this so there's
lots of other benefits that come with it
other than just getting something out to
market
so current materials like bioactive
glasses and synthetic glass
substitutes our aim to repair so you
know you put it in they recruit the host
cells or the patient cells and they
form new bone and they degrade away and
then you get new bone regenerated in
that space but the future direction
might be one where we would do this
regeneration of new bone in the lab or in
a clinical environment and when the
patient comes in for their surgery you
would actually have a precursor or a
graft with cells blood vessels and
premature bone formed in it ready to
implant into the different defects so
this is called tissue engineering so
you're engineering the tissue outside
the body right so this would involve
putting materials cells and growth
factors or biomolecules in the right
environment that could be a blood flow
to stimulate the flow in bone
compression like mechanical deformation
to simulate how somebody might load bone
in their body to generate the right
bone before it can be implanted and so
there's lots of benefits to this
over putting a material in your body and
getting new bone forming there and one
day you know if tissue engineering
achieves the goals or the promise that
it's showing one day you might
go into a doc clinic and
there will be a 3D printer that the
surgeon would be able to print all sorts
of different parts that are matched to
you to your own biology and then will
be implanted within and then you
know they they'd be designed in a way
that would allow you to go back to
your daily life and with a few
days at the hospital and you know those
advances would be
possible if tissue engineering delivers
what it promises so this looks like
something out of a Frankenstein movie to
me yeah I guess something similar but I
guess in this case you know Mo yeah
we've got lots of developments that
proves this might be
possible one day yeah right so you know
there's loads of advances in
like diagnostics and genetics and so on
that allow us to map a patient makeup
genetic makeup and we have lots of
understanding on how cells develop into
two different tissues and how disease
affect this tissue and you know
tissue engineering we've achieved
significant like lots of new things
we've discovered so many new things with
tissue engineering and at the moment we
can create small tissue patches in the
lab and if you can put all of those
together and with new advances in 3D
printing capabilities one day we might
be able to do this but may make it
probably maybe another 50 years we might
just see something like this in a
clinical environment this is the
direction that biomaterials is going in
and something important for our students
to learn about isn't it yeah you're
right and even if it's not for
implantation being able to produce a
patch of tissue say maybe like a
centimeter by centimeter by centimeter
patch of tissue in a lab that matches
the human like you know the architecture
of the human tissue is made of the human
cells that allows you to test medicines
and it allows you to test drugs and it
allows you to do that better than using
animals right so
in drug development pipeline a lot
you know to take one single drug into
market
apparently pharmaceutical companies
spend between two to four billion
dollars U.S. dollars right for one
single drug into market and they start
off with maybe like a hundred thousand
drugs that they screen in vitro and then
they go into animal testing and then
they take ten for clinical trials and
nine fails and only one makes it through
into clinic and they spend a lot of time
and a lot of money developing it
most of the drugs fail really
at the right last minute like at the end
when they're testing on humans so if you
can do some of those testing in the lab
on tissue patches that really closely
mimic the human environment then you can
kind of screen a lot more drugs early on
and have better hits so you save on time
and you save a lot of money and you get
more drugs out into the market into the
clinical environment so even if it's if
tissue engineering doesn't deliver
implantable grafts you might it's
starting already to deliver and models
tissue models of bone liver lungs and
people are even developing lung models
to do COVID testing and studying
COVID and how Coronavirus actually
propagates through the lung and attaches
onto the lung walls and how it causes
all the inflammation so tissue
engineering would at least contribute in
the sense of developing new models which
can be used to study diseases and
drug development
so yeah I guess with that and now yeah
thank you all for your attention and if
you have any questions hang around
and put them on the question Q&A and
we'll be able to answer those
