Surface modification of PMMA IOLs by the immobilization of hydroxyethyl
methacrylate for improving the biocompatibility
Yanlin Wei and Yashao Chen*
Key Laboratory of Applied Surface and Colloid Chemistry (Shaanxi Normal University), Ministry of Education,
School of Chemistry and Materials Science, 710062, Xi'an, China
*E-mail address: [email protected]
Abstract: To improve biocompatibility of hydrophobic polymethyl methacrylate
intraocular lens (PMMA IOL), 2-hydroxyethyl methacrylate (HEMA) was
immobilized by UV-induced graft copolymerization method. The hydrophilicity
and chemical composition of the PMMA IOL surface after each step of surfaces
modification were analyzed by contact angle (CA) and X-ray photoelectron
spectroscopy (XPS). The morphology of the IOL surface was characterized by
atomic force microscopy (AFM). The results revealed that the hydrophilicity of
the HEMA-g-PMMA IOL samples were significantly and permanently improved.
The surface biocompatibility of the modified IOL was evaluated by platelets
adhesion experiments.
Keywords: Surface modification, UV-induced, 2-hydroxyethyl methacrylate,
biocompatibility
1. Introduction
In ophthalmology, PMMA is the gold standard
material for use in IOL manufacturing and still used
today in some parts of the world for the production
of IOL due to its cost-effective, offering lens
stability and reliable optical performance. However,
PMMA IOL is hydrophobic and hard, which are
easy to adhering bacteria and cells. These
disadvantages limit its wide applications. Therefore,
the surface modification of PMMA IOL may be a
promising
approach
to
enhance
their
biocompatibility
and
reduce
implantation
complication. The HEMA as a nontoxic,
nonimmunogenic, and nonantigenic biocompatible
material is the excellent candidate for the
preparation
of
various
biomedical
and
pharmaceutical components [1, 2], e.g., implants,
drug delivery devices, support for enzyme
immobilization. The material’s unique structural
properties such as its aqueous hydrogel formation
and biodegradability have made it a desirable
material for replacement tissue scaffolding
applications as well. In addition to these properties,
HEMA is optically transparent when hydrated,
which is of the utmost importance for materials to be
used as optical devices.
Over the past three decades, various techniques
such as plasma processing [3], chemical grafting [4],
and ion implantation [5] have been applied to the
surface modification of PMMA IOL. Among these
works, immobilization of active biomacromolecules
on the surface of PMMA IOL is one of the most
successful methods to enhance biocompatibility. Qu
et al. have immobilized alpha-Allyl glucoside on
PMMA
IOL
surface
by
plasma-induced
polymerization to improve the hydrophilicity of the
anterior surface of the PMMA IOL and reduce the
cell attachment [6].
In the present work, HEMA was immobilized on
the surface of hydrophobic PMMA IOL by two-step
methods to enhance the resistance of platelets.
Firstly, PMMA IOL was pretreated by oxygen
plasma. Then the surface modification of oxygen
plasma-pretreated PMMA IOL was carried out via
UV-induced graft copolymerization with HEMA.
The hydrophilicity, chemical composition, and
morphology of the modified PMMA IOL surface
were evaluated by CA, XPS, and AFM. The
biocompatibility was carefully evaluated by
adhesion experiments of platelets.
2. The experimental system
3. Results and discussion
The PMMA IOL samples were thoroughly
cleaned with anhydrous ethanol for 5 min in an
ultrasonic bath. They were pretreated with oxygen
plasma before being subjected to UV-induced graft
copolymerization with HEMA. A cylindrical type
glow discharge cell, Model SY-300, manufactured
by the Institute of Microelectronics, Chinese
Academy of Science, was used for the plasma
pretreatment. The plasma power applied was kept at
40 W at a radio frequency of 13.56 MHz. The
samples were placed between the two parallel
electrodes (separation 6 cm) and subjected to the
glow discharge for a predetermined period of time at
an oxygen pressure of 40 Pa. The oxygen plasmapretreated PMMA IOL samples were then exposed
to the atmosphere to affect the formation of surface
peroxide and hydroperoxide species before graft
copolymerization [7].
The UV-induced surface graft copolymerization
with HEMA was carried out in a model XPA-5
photochemical reactor, manufactured by Xujiang
electromechanical plant, Nanjing, China. The reactor
was equipped with a 500 W high-pressure Hg lamp
and a constant-temperature water bath (25 °C). The
oxygen plasma-pretreated PMMA IOL samples were
immersed in 20 mL of aqueous solution of HEMA in
a Pyrex tube. The HEMA monomer concentration
was varied from 1 to 20 wt. %. Each reaction
mixture was thoroughly degassed and sealed under a
nitrogen atmosphere. It was then subjected to UV
irradiation for 30min. After each grafting experiment,
the PMMA IOL samples were extracted by Soxhlet
extractor with 75 % ethanol to remove the residual
monomer and physically adsorbed homopolymer.
The process of surface modification of the oxygen
plasma-pretreated PMMA IOL via UV-induced graft
copolymerization
with
HEMA
is
shown
schematically in Fig. 1.
3.1 Hydrophilicity of the modified IOL surfaces
To optimize the conditions, HEMA with different
concentrations (1.0, 5.0, 10.0 and 20.0 wt. %,
labeled as HEMA1-g-PMMA, HEMA5-g-PMMA,
HEMA10-g-PMMA and HEMA20-g-PMMA) were
independently grafted onto the PMMA IOL surfaces,
and their hydrophilicity variation was monitored by
CA in the hydrated state. As shown in Fig. 2, the CA
of pristine PMMA IOL surface was 76.5 °,
presenting an obvious hydrophobic character. With
the increasing of UV graft copolymerization time,
the CA values of PMMA IOL surface modified by
different concentrations HEMA declined, especially
in 5.0 wt. %. The decline of CA values subsequently
shows a tendency toward stabilization after the graft
time reached 30 min, revealing equilibrium between
the polar group from the immobilization of the
hydrophilic HEMA and the surface plasma etching.
In detail, taking the case of 30 min UV graft
copolymerization
time,
as
the
monomer
concentration increased from 1.0 to 20.0 wt. %, the
CA values of HEMA-g-PMMA IOL surfaces firstly
decreased with increasing monomer concentration,
especially for the HEMA5-g-PMMA IOL sample
reaching the lowest point of the 28.6 °. At the high
monomer concentration of 10.0 wt. % or above,
excessive homopolymerization in the reaction
mixture prevents the grafting of PMMA IOL
samples. The CA value of HEMA20-g-PMMA IOL
surface is on the order of 45.5 °, compared to about
76.5 ° for the pristine PMMA IOL surface. This
observation is consistent with the hydrophilic nature
of the HEMA polymer [8].
Figure 1: Schematic diagram illustrating the processes of
surface modification of oxygen plasma-pretreated PMMA IOL
via UV-induced graft with HEMA
Figure 2: Effect of the UV graft copolymerization time on the
contact angles of HEMA-g-PMMA IOL with different HEMA
concentrations: (a) 1.0; (b) 5.0; (c) 10.0; and (d) 20.0 wt. %
3.2 Surface component analysis of the modified
IOL surfaces
The presence of the grafted HEMA polymer on
the oxygen plasma-pretreated PMMA IOL samples
under the present reaction conditions is also
confirmed by XPS. Figure 3 shows the typical XPS
survey spectra of pristine PMMA IOL, oxygen
plasma-pretreated PMMA IOL and HEMA5-gPMMA IOL. Two strong peaks of C1s and O1s, and
one weak peak of N1s were observed on all the IOL
surfaces regardless of surface modification. It is no
doubt that C1s and O1s are the main elemental
compositions of the PMMA IOL. The N1s element
found in the pristine PMMA IOL comes from the
ultraviolet-absorbent in the IOL. Compared with the
unmodified PMMA IOL, it can be seen that surface
modification induces an obvious increase in the peak
intensity of O1s and a slight enhancement of N1s
peak. It indicates that both oxygen and nitrogen
elements on the IOL surface increase after the
surface modification, concomitant with a decrease in
carbon element (Fig. 3b and 3c). These results
suggest the introduction of oxygen and nitrogencontaining polar functionalities onto the surface
modified IOL surface.
Figure 3: Survey XPS spectra of (a) PMMA IOL; (b) oxygen
plasma-pretreated PMMA IOL; and (c) HEMA5-g-PMMA IOL
3.3 Surface morphology of the modified IOL
surfaces
Topography is an essential issue for PMMA IOL
surfaces, as it is directly related to protein adsorption
and eventually, cell adhesion and proliferation [9].
The morphology and nanostructure of the PMMA
IOL surfaces were analyzed by AFM. Detailed realspace topographical information on the surface
features was provided in terms of interface
roughness values. The three-dimensional AFM scans
are given in Fig. 4. The pristine PMMA IOL surface
was relatively smooth, with small and equally
distributed granular features (Fig. 4a). However,
after the oxygen plasma-pretreatment, peak-like,
uneven features were found on the samples (Fig. 4b).
After being modified by 5.0 wt. % HEMA solution,
the PMMA IOL surfaces showed a correspondingly
flattened character which was similar to the pristine
PMMA IOL (Fig. 4c). Hence, to a certain extent,
HEMA apparently filled in the asymmetries and
smoothed the surface topography [10, 11].
(a)
(b)
(c)
Figure 4: AFM images of the (a) PMMA IOL; (b) oxygen
plasma-pretreated PMMA IOL; and (c) HEMA5-g-PMMA IOL
3.4 Biocompatibility evaluation of the modified
IOL samples
As a foreign body in the eye, the IOL must
possess excellent blood compatibility, so the
quantity and the morphology of the adhered platelets
are considered to be early indicators of IOL
biocompatibility [12]. Figure 5 shows a great
number of uniformly distributed platelets adhering
on pristine PMMA IOL, most of them deformed and
with pseudopodia stretched out to stick to the IOL
surface, a few of which were completely flattened
and in a highly activated phase. However, in the case
of oxygen plasma-pretreated PMMA IOL and
HEMA5-g-PMMA IOL, platelets were scarcely seen,
and appeared to be in an inactive state. Especially
for the HEMA5-g-PMMA IOL, the platelets were
mostly round and small, except for a few with tiny
pseudopodia. These results suggest that platelet
adhesion on the IOL surface was significantly
inhibited after HEMA surface modification.
Acknowledgments
The authors are grateful to Dr. D. C. Chen for his
helps in XPS analysis. This research has been
partially supported by the Fundamental Research
Funds for the Central Universities (Grant no.
GK201004001, GK200901023).
References
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Figure 5: SEM images of platelets adhering on the IOL samples:
(a) PMMA IOL, ×2500; (b) PMMA IOL, ×5000; (c) oxygen
plasma-pretreated PMMA IOL, ×2500; (d) oxygen plasmapretreated PMMA IOL, ×5000; (e) HEMA5-g-PMMA IOL,
×2500; and (f) HEMA5-g-PMMA IOL, ×5000
4. Summary
A more convenient, economical and continuous
method for covalently grafting HEMA onto the
functionalized surface of PMMA IOL was
developed. The variations in the elemental
composition of the modified IOL surface were
assessed by XPS, and provided evidence for the
HEMA-grafting. No apparent damage was detected
on the HEMA-g-PMMA IOL surfaces, but a
corresponding flatter feature was observed compared
with the oxygen plasma-pretreated. Cell adhesion in
vitro assays demonstrated that the HEMA5-gPMMA IOL significantly reduce the adhesion of
platelets. These preliminary results demonstrate that
monomer graft modification by UV-induced graft
copolymerization is a promising application field,
and this technology will probably immensely
contribute to the further industrial manufacture and
clinical application.
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