1. Scientists from the University of Leeds developed a peptide called P11-4 that can self-assemble to form a three-dimensional matrix that mimics the enamel matrix. 2. This matrix initiates the biomineralization process to regenerate enamel within caries lesions. Calcium and phosphate ions from saliva crystallize around the peptide matrix. 3. Studies show P11-4 application can reverse caries progression and stimulate the formation of new enamel, avoiding later invasive treatments. The peptide technology, commercialized as Curodont, has received CE certification.

1. P11-4 nano-fibres
(Curodont ™). × 120 000.
Picture: A. Aggeli and
S. Maude, Leeds
Regenerating teeth
The new dimension of Self-Assembling Peptides

2. 3 4
21
200 nm
20 um
150 nm
Monomer Fibre

3. Up to now there was no method available in
dentistry to regenerate enamel tissue.
.. Enamel does not contain any cells,
that could form new tissue.
.. Initial caries occurs underneath the hyper­
mineralised plate where demineralisation
progresses unopposed.
.. Enamel does not contain any matrix which
could support de novo biomineralisation.
During odontogenesis the three-dimensional
amelogenin matrix enables crystallisation
and ordered calcium phosphate crystal growth.
The matrix is subsequently degraded.
Scientists from the University of Leeds found
a way to mimic the enamel matrix within
­enamel lesions and thus enabling regeneration
via de novo biomineralisation: Self-Assembling
Peptides.
Self-assembly
In nature self-assembly is widespread. The best
known examples are the spontaneous folding
of proteins or the formation of the double helix
from two DNA strands.
Molecular self-assembly enables production
on the nanometer scale. It is the basis of nano-
technology and has opened up the field for
many new techniques and products in material
and pharmaceutical sciences.
Self-Assembling Peptides are especially indicated
for their use in biological systems. Correspon-
ding to their individual design they can fulfil
various biological functions and substitute for
three-dimensional matrices. They are widely
used in tissue engineering and for the produc-
tion of three-dimensional cell cultures.
Enamel:
no regeneration without matrix
Self-Assembling Peptides mimic the enamel matrix.
The peptides form a three-dimensional network within the lesion to build
a matrix, initiating biomineralisation.
1 Matrix enables crystallisa-
tion: Atomic Force Microsco-
py picture during the devel-
opment of a hydroxya­patite
crystal with amelogenin
­self-assembling nanospheres
(white arrow) around it.
Reproduced with permission
from Kirkham (2000) J Dent
Res.
2 Subsequent degradation
of the matrix: Atomic Force
Microscopy picture after
­partial stripping of the
amelogenin nanospheres
(white ­arrows). The immature
hydroxyapatite is visible
with the remaining matrix.
J. Kirham, Leeds
3 No regeneration without
matrix: Enamel is almost
completely composed of
­calcium-phosphate crystals.
Regeneration of the enamel –
similar to its development
during odontogenesis – is
therefore not possible.
S. Brookes, Leeds
4 Self-Assembly: Monomers
spontaneously form a sheet
which itself forms higher
molecular structures e.g.
­fibres.
1. Formation of the organic amelogenin
matrix (self-assembling nanospheres):
Crystal-nucleation and regulation of the
crystal growth by the matrix
Enamel formation during odontogenesis
2. Degradation of the matrix
3. Crystal maturation

4. Mineral change μg/mm2
40 P11-4 control
30
20
10
0
-10
-20
net
** ** ** ***
day 1 day 2 day 3 day 4 day 5
lossgain
2
4
6
1
3
5
87
100 nm
Carious lesion

5. Scientists from the University of Leeds have developed a patented
technology for the regeneration of enamel: P11-4. The monomers of
Peptide P11-4 form spontaneously a biocompatible three-dimensional
matrix that mimics the enamel matrix. Around the newly formed ma-
trix de novo enamel-crystals are formed from calcium phosphate from
saliva. The process uses the natural remineralisation process, that is –
in a healthy tooth – in constant equilibrium with demineralisation.
15 years of research
The research groups in Leeds have published in the past 15 years a
­series of scientific papers about P11-4 in various journals, e.g. Nature.
The revolution in initial caries therapy: P11-4 (Curodont ™)
.. Mimicking the enamel matrix and the initiation of tooth
­regeneration via biomineralisation
.. Reversal of the caries progress towards remineralisation
.. Three-dimensional regeneration of early enamel lesions
.. Avoiding subsequent invasive caries treatments
Formation of new enamel
Regenerating carious lesions instead of repairing them.
With the help of Self-Assembling Peptides dentists can stimulate
the regeneration of the tooth and avoid later invasive therapies.
1 Initial caries defect: the
hypermineralised plate co-
vers the initial defect.
2 Diffusion into the defect:
Monomeric P11-4 is applied
onto the lesion and diffuses
through the pores of the
hypermineralised plate into
the subsurface lesion body.
3 Formation of the matrix:
The peptide monomers
­spontaneously form a three-
dimensional matrix via
­hydrogen bonds.
4 Biomineralisation: Crys-
tallisation around the matrix.
Calcium phosphate from
­saliva crystallises around the
matrix, forming new enamel.
5 Self-assembly: P11-4
­monomers forming a fibril
network. In vitro experiment.
TEM.
Reproduced with permission
from Kyle (2010) Biomaterials.
6 More mineralisation with
P11-4 (Curodont ™): Effect
of P11-4 on the re-, and
­de-mineralisation of carious
lesions in human enamel in
a pH-cycling ­experiment.
The total mineral gain (left
bar) as well as mineral gain
on 4 out of 5 days is signifi-
cantly higher with P11-4
than with the control (n=8).
Graphic according to Kirk-
ham (2007) J Dent Res.
7 8 Single application of
P11-4 (Curodont ™): The
white spot lesion is strongly
reduced after 6 months.
Left: prior to treatment.
Right: 6 months after treat-
ment.
Photos: Paul Brunton, Leeds
.. Aggeli, A., M. Bell, et al. (1997). «Responsive gels
formed by the spontaneous self-assembly of peptides
into polymeric beta-sheet tapes.» Nature 386(6622):
259-262.
.. Aggeli, A., M. Bell, et al. (2003). «pH as a trigger
of peptide beta-sheet self-assembly and reversible
switching between nematic and isotropic phases.»
J Am Chem Soc 125(32): 9619-9628.
.. Bell, C. J., L. M. Carrick, et al. (2006). «Self-assembling
peptides as injectable lubricants for osteoarthritis.»
J Biomed Mater Res A 78(2): 236-246.
.. Brunton, P. A., R. P. Davies, et al. (2012). Self-assembling
peptides to support remineralisation of tooth lesions –
a biomimetic approach. ICNARA2. Vina de Mar, Chile.
.. Davies, R. P. and A. Aggeli (2011). «Self-assembly of
amphiphilic beta-sheet peptide tapes based on aliphatic
side chains.» J Pept Sci 17(2): 107-114.
.. Felton, S. (2005). Self assembling β-sheet peptide
networks as smart scaffolds for tissue engineering.
Chemistry. Leeds, University of Leeds. PhD: 184.
Scientific literature – 15 years of research
.. Kirkham, J., A. Firth, et al. (2007). «Self-assembling
peptide scaffolds promote enamel remineralization.»
J Dent Res 86(5): 426-430.
.. Kirkham, J., J. Zhang, et al. (2000). «Evidence for
charge domains on developing enamel crystal surfaces.»
J Dent Res 79(12): 1943-1947.
.. Kyle, S., A. Aggeli, et al. (2010). «Recombinant
self-assembling peptides as biomaterials for tissue
engineering.» Biomaterials 31(36): 9395-9405.
.. Kyle, S., A. Aggeli, et al. (2008). «The self assembling
peptide, P11-4 for a scaffold in regenerative medicine.»
Eur Cell and Materials 16(Suppl 3): 70.
.. Scanlon, S., A. Aggeli, et al. (2009). «Organisation of
self-assembling peptide nanostructures into macroscopi-
cally ordered lamella-like layers by ice crystallisation.»
Soft Matter 5: 1237-1247.
.. Wilshaw, S. P., A. Aggeli, et al. (2008). «In vivo
assessment of the immunogenicity of self-assembling
peptides for use in regenerative applications.» Eur Cell
and Materials 16(Suppl 3): 97.

6. Relative cellular ATP-content
108
107
106
105
104
103
P11-4 collagen
day 0 day 7 day 14 day 21 day 28
3
1 2
100 nm

7. The high biocompatibility of P11-4 has
been demonstrated in numerous cytotoxi­
city, in vivo implantation, local and
­systemic immunogenicity as well as histo-
pathological studies.
CE-label
The technology has been found to be
safe and has been approved for clinical
use within Europe. The production of
­Curodont™ is performed under highest
cGMP standards indicated for pharma­
ceutical products.
Safety and biocompatibility
Revolutionising caries treatment via regeneration.
Enamel regeneration with Self-Assembling Peptides enables a completely
new treatment option for initial caries.
3 Cooperation with experi-
enced partners: The technical
development and the produc-
tion have been performed in
close collaboration with esta-
blished pharmaceutical and
biotech companies.
2 Similar cell compatibility
as collagen type I: Prolifera-
tion of L929 cells over 28
days, measured by the ATP-
content of the cells. Average
(n=9) +/- 95% CI.
Reproduced from Kyle (2008)
Eur Cell and Materials.
1 Good biocompatibility:
Cytotoxicity test. Microsco-
pic picture of L929 fibroblast
cells growing for 48h in
­direct contact with P11-4.
The white arrow indicates
the contact between cells
and P11-4. × 200.
Reproduced with permission
from Kyle (2010) Biomaterials.
credentis was founded in 2010 by Dr.
­Dominik Lysek to develop and bring into
the dental market the innovative techno­
logy of Self-Assembling Peptides. As a first
step Curodont™ is launched as a product
in cariology. This has been achieved in close
collaboration with experienced partners
in academia and industry.
Regeneration instead of repair: our mission
The treatment of initial carious lesions
is the first application of Self-Assembling
Peptides in patients – bringing with them
the potential to revolutionise preventive
dentistry, as from now on, dentists can
­regenerate caries affected enamel.
1997
1998
2007
2003/04
2010
2012
1st
publication. Self-Assembling
Peptides form a 3D-matrix.
Aggeli (1997) Nature
1st
patent family covering
Self-Assembling Peptides.
Biocompatibility tests.
Various publications
Start of the clinical deve-
lopment in dentistry.
­Kirkham (2007) J Dent Res
Initiation of the 1st
Clinical
study for the effect in
­enamel regeneration.
Brunton (2012) ICNARA2
Market approval
of Curodont ™.

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