Innopitch presentation 2014

1. Self-­‐lubrica,ng
scaffolds
Ronit
Goldberg
Sabrina
Jahn

2. Background
• debilita6ng
joint
disorder
•
affec6ng
>
40mio.
pa6ents
in
the
US
in
2012
• Expected
↑
in
prevalence
• Sufferers
experience
pain
and
restric6ons
in
mo6on
Ø due
to
degrada6on
of
ar6cular
car6lage
and
subchondral
bone
Ø Limita6on
in
load
transmission
and
lubrica6on
while
ar6cula6on
Osteoarthri,s
(OA)
Current
therapeu,c
strategies
• Limited
to
symptoma-c
therapy!
Ø Analgesics
Ø Surgery:
complete
or
par6al
joint
replacement
• Tissue
engineering
approaches
under
clinical
trials
• No
Healthy
synovial
joint
damaged
car6lage
OA
synovial
joint
Es,mated
market
…
for
regenera6ve
products:
$9.9billion
in
2011
and
expected
$32
billion
by
2018*
approach
suggested,
which
could
regenerate
the
interfacial
lubrica,on
proper,es
of
the
joint!
*Agarwal,
A.,
Tissue
Engineering
and
Regenera6ve
Medicine,
Vol
10
(4),
pp155-­‐159,
2013

3. We
aim
to
develop
polymer-­‐based
scaffolds
incorpora6ng
self-­‐lubrica-ng
macromolecular
vectors
for
high
pressure
environments.
Ø To
mimic
low
fric-on
and
lubrica-on
naturally
occurring
at
healthy
human
knee
or
hip
joints
Ø Poten6al
therapy
to
repair
car6lage
lesions
of
OA
pa6ents
via
an
injec6on
into
the
synovial
cavity
The
Idea
Advantages:
• Avoid
surgery
Ø lower
costs
for
health
care
providers
Ø Use
of
biocompa6ble
materials
• no
obvious
side
effects
Polymer matrix

4. • Liposomes
The
system:
Lubrica6ng
vectors
are
spherical
structured
par6cles
composed
from
biological
lipid
molecules.
• Their
size
range
from
0.1
μm
to
1
μm
• Most
of
their
volume
is
occupied
by
water.
Liposome
Liposomes
Lipid
molecule
Liposome
lubrica,on
on
surfaces
• Experiments
showed
that
liposome
adsorp6on
onto
solid
surfaces
reduced
fric6on
down
to
the
noise
level
of
the
system.
List
of
published
papers:
§ R.
Goldberg
..
and
J.
Klein,
Advanced
Materials,
2011,
23,
(31),
3517-­‐3521.
§ R.
Goldberg
..
and
J.
Klein,
Biophysical
J,
2011,
100
1-­‐9.
§ R.
Goldberg,
J.
Klein,
Chemistry
and
Physics
of
Lipids,
2012,
165,
374–
381.
• The
extremely
efficient
lubrica6on
was
observed
under
high
loads
of
120
atm
and
more.

5. The
system:
Scaffolding
matrix
0.60 #
0.15/1 0.5/2.3 1/5.6 3/16.9 5/28.2 7/39.5
0.45
0.30
0.15
0.00
#
#
#
T
=
25
cels ius
F riction
measurements
μ
L oa d
[K g ]
/
P
[a tm]
neat
+
lipo
A
+
lipo
B
• HEMA
HEMA
hydrogels
hydrogels
are
biocompa6ble
and
nontoxic.
• They
contain
about
40%
water.
• HEMA
hydrogels
were
prepared
with
adding
different
lubrica6ng
liposomal
vectors
before
curing.
• Fric6on
Fric,on
measurements
tests
were
preformed
using
a
tribometer.
• The
fric6on
coefficient
was
measured
for
a
hydrogel
vs.
metal
system
at
pressures
from
0.5
to
40
atm.
poly-­‐HEMA
Friction coefficient μ is reduced up to
a factor of 60!
Tribometer
set-­‐up

6. Microscopic
imaging
of
the
system
Neat
HEMA
HEMA
+
lubrica6ng
vectors
• Neat
HEMA
hydrogels
show
featureless
fracture
images.
• HEMA
hydrogels
with
incorporated
lubrica6ng
vectors
showed
remarkable
organiza6on
inside
the
hydrogel
fracture.

7. …
to
obtain
low
fric6on
between
mutually
sliding
surfaces
in
aqueous
environments
• Hydra6on
The
Mechanism
behind
it…
layers
form
around
charged
or
zwilerionic
groups
of
the
vector
• under
shear,
the
compressed
hydra6on
layer
responds
in
a
fluid
manner
Ø sliding
surfaces
can
sustain
a
large
normal
load
while
maintaining
their
strongly
alached
hydra6on
layers.
*
U.
Raviv
and
J.
Klein,
Science
2002,
1540,
297
δ+
δ+
H
H
O
H2O
δ-­‐
Experiments
revealing
this
effect:
• Nanotribological
Surface
Force
Balance
(SFB)
studies*
• Allow
measurement
of
shear
(Fs)
and
normal
forces
(FN)
• Force
sensi6vity
of
10nN
• Distance
resolu6on
about
0.1nm
U.
Raviv
et
al.,
Nature
2003;
425,
163
D0 Fs
Fn
x0
D1
x1
Chen
M.
et
al.,
Science
2009;
323,
1698-­‐1701
decreasing distance D
Hydra,on
Lubrica,on

8. Compe66ve
advantage
IPR:
• Phosphotadylcholine
Lipid
Liposomes
as
Boundary
Lubricants
in
Aqueous
Media;
Priority
June
17,
2010;
PCT
filed
on
June
16
2011
WO2011/158237),
Na6onal
Phase
entered:
US,
Europe,
Canada,
Israel
and
Brazil.
Team:
• Ronit
Goldberg,
PhD
and
Sabrina
Jahn,
PhD:
strong
academic
background
in
biotechnology,
material
sciences
and
biophysics
• Scien6fic
advisor:
Professor
Jacob
Klein:
world-­‐leading
expert
in
polymer
physics
and
biological
lubrica6on
Knowledge:
• Iden6fica6on
of
mechanism
of
lubrica6ng
vectors
and
hence
tes6ng
of
lubricious
substances
on
a
nanotribological
scale
accomplished
via
an
ultrasensi6ve,
custom-­‐built
technique
Ø difficult
for
compe6tors
to
reproduce

9. Funding
needs
Research
material
costs:
• Fabrica6on
of
lubricious
scaffolds
under
GLP/GMP
condi6ons
for
preclinical
studies
• Es6mated
costs:
~€25.000
and
~
€25.000
for
outsourcing
Preclinical
study:
• Cost
of
animals
(ini6ally
rats,
then
larger
animals),
“Pilot”
trial:
establishing
appropriate
experimental
design
condi6ons;
assessing
both
the
efficacy
and
pre-­‐clinical
safety;
~
20
animals;
“Main
study”:
car6lage
lesion
induc6on,
biocompa6bility,
toxicity,
reten6on
6me
studies
of
lubrica6ng
vectors,
histology,
follow-­‐up
of
animals
over
a
period
of
6
months
including
behavioral
tes6ng,
80
animals
• Es6mated
costs:
~€
200.000
Personnel:
• 2
senior
scien6sts,
2
PhD
level
scien6sts,
technical
staff
over
2
years
• Es6mated
costs:
~€450.000

10. Economic/social
impact
• Improve
mobility
of
the
older
genera,on!!!
Ø possibility
to
work
up
to
older
ages
Ø later
pension
Ø Improve
social
costs
Ø Reduce
health
care
costs