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face of the abutment in the area of the emergence profile
(area between bone and gingiva level) play an important role.
The material of the abutment should be biocompatible and, in
the optimal case, should exhibit good adhesion to the adjacent
tissue. The coating of the implant surface in the area of the
emergence profile of the gingiva could prevent bacterial
adhesion and formation of a biofilm, thus reducing the risk of
penetration into the tissue and subsequent infection.
In the present work we developed a functional polymer
coating with antimicrobial properties against various oral
pathogens, and attractive adhesion properties for fibroblast
and stem cells (Scheme 1). To design bioactive coatings, we
group of isoeugenol.[37,38] For this reason, eugenol molecules
were conjugated with linear hydrophilic spacers having
terminal polymerizable acrylate groups to form functional
macromonomers following two strategies (see the Supporting
Information for more details). The first synthesis strategy
(Figure 1a; route A) was based on direct anionic polymeri-
zation of the protected glycidol monomer ethoxy ethyl
glycidyl ether (EEGE) using the hydroxyl groups of eugenol
as the initiating moiety, followed by modification of the
terminal hydroxyl groups by acryloyl chloride and deprotec-
tion of glycidol segments. The synthesis of oligoglycidol
macromonomers with variable chain length and architecture
was reported in our previous work.[39] During the synthesis,
eugenol isomerized to isoeugenol due to the basic conditions
of the living anionic polymerization.[40–42]
The second synthesis strategy (Figure 1a; route B) was
based on the modification of hydroxyl groups of isoeugenol
with chloroacetic acid, followed by the direct coupling of
hydroxyl-terminated PEG-methacrylate. The attachment of
a hydrophilic spacer with a terminal polymerizable group to
isoeugenol has several advantages: a) improvement of the
water-solubility of isoeugenol; b) minimization of the risk of
isoeugenol leaching from nanogels; c) regulation of accessi-
bility of isoeugenol on the nanogel surface by variation of the
spacer length. Synthesized isoeugenol-decorated macromo-
nomers were directly used as co-monomers in the precipita-
tion polymerization of N-vinylcaprolactam (VCL) to obtain
biocompatible functional nanogels (Figure 1a). Hydrophilic
macromonomers stabilize formed nuclei during precipitation
polymerization and finally are localized on the nanogel
surface.[43] In this situation, nanogels consist of a PVCL core
surrounded by a macromonomer-rich shell. Therefore, active
eugenol molecules are present on the nanogel surface and are
directly exposed to the aqueous phase. The developed
synthetic route allows for the synthesis of monodisperse
spherical colloidally stable nanogels with a tunable particle
size (100 nm–500 nm) (Figure 1c). The presence of the
macromonomers on the nanogel surface was determined by
X-ray photoelectron spectroscopy (XPS). It was found that
the amount of isoeugenol-decorated macromonomers on the
nanogel surface could be effectively varied by the variation of
macromonomer concentrations during the nanogel synthesis
step (Figure 1b). The experimental data indicate that increas-
ing the spacer length from 4 to 12 repeating units results in an
increase in the incorporation of macromonomers into the
nanogel surface, at a constant concentration in the polymer-
ization mixture.
Scheme 1. General concept of the bioactive nanogel coating for dental
implants.
used functional nanogels as building blocks. Nanogels are
macromolecules that combine unique properties such as high
chemical functionality,[25,26] swelling in water,[27] and biocom-
patibility[28,29] along with strong adsorption on different
surfaces and the formation of dense layers with well-defined
thickness and morphology.[30–32] The nanogels used in the
present work exhibit the functional surface bearing hydro-
philic polymers poly(ethylene glycol) (PEG) or poly(glycidol)
(PG) to ensure anti-biofouling properties, as well as cova-
lently bound antibacterial molecules. The ultimate goal is to
design nanogel-based coatings that determine the outcome of
the “race for the surface” in dental implants between human
gingival fibroblasts and different oral pathogens: fibroblasts
should win and pathogens should lose.
The chemical design of the nanogels is presented in
Figure 1a. Eugenol extracted from cloves is known for its
antiseptic, antibacterial properties[33] and is an important
component of some dental cements.[34] In the frame of this
work we decided to use isoeugenol instead of eugenol due to
its higher antibacterial activity[35] and the fact that it is not
genotoxic, in contrast to eugenol.[36] Although isoeugenol is
a stronger allergen than eugenol, the underlying mechanism
proposed to be responsible for those properties is no longer
possible due to the conjugation of a spacer at the alcohol
This supports the hypothesis that macromonomer hydro-
philicity plays an important role in the stabilization of
growing nuclei during nanogel synthesis.[27] However, an
increase of the spacer length to 41 and 200 repeating units
resulted in the opposite effect, leading to lower incorporation
at the particle surface (only 2–5%). For the design of
bioactive coatings, we synthesized a series of nanogels with
a controlled amount of surface-bound isoeugenol as shown by
Raman spectroscopy (Figure 1d). The interesting part of the
spectrum ranges from 1800 to 1500 cmꢀ1. In this region, four
main signals are identified. The signal at 1728/1730 cmꢀ1
=
results from the vibration of C O bond within the ester
2
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Angew. Chem. Int. Ed. 2017, 56, 1 – 7
These are not the final page numbers!
Kather, Michael
