Development of hydrogel lenses with surface-immobilized PEG layers to reduce protein adsorption

Article abstract of DOI:10.1002/bkcs.10545

This paper describes the synthesis and characterization of a series of poly(2-hydroxyethyl methacrylate) (pHEMA)-based hydrogel lenses coated with poly(ethylene glycol) (PEG) chains. A novel tri-branched PEG-substituted hydrazide is synthesized, which imparts densely packed, covalently bound PEG layers on hydrogels, to determine whether branching provides improved coverage of the lens surface, thereby reducing protein adsorption. Surface modification of hydrogels with PEG was performed via amide-coupling reactions between PEG-substituted hydrazide and the pHEMA matrix. Protein adsorption, water content, optical transparency, and surface properties of the hydrogels were investigated. The hydrogels exhibited transmittance of >90% and improved surface hydrophilicity. Notably, the amount of lysozyme adsorbed on tri-branched PEGcoated hydrogels decreased significantly compared to the amount adsorbed onto the surface of control and linear PEG-coated hydrogels. These results provide insight into the mechanism by which PEGs reduce lysozyme adsorption and suggest that PEG coating may offer an intriguing potential for ophthalmic biomaterials as well as protein-resistant devices.

Full text of DOI:10.1002/bkcs.10545

Article
DOI: 10.1002/bkcs.10545
BULLETIN OF THE
J.-P. Jee and H.-J. Kim
KOREAN CHEMICAL SOCIETY
Development of Hydrogel Lenses with Surface-immobilized PEG Layers
to Reduce Protein Adsorption
Jun-Pil Jee† and Ho-Joong Kim‡,
*
†College of Pharmacy, Chosun University, Gwangju 501-759, Korea
‡Department of Chemistry, Chosun University, Gwangju 501-759, Korea. *E-mail: hjkim@chosun.ac.kr
Received May 28, 2015, Accepted July 22, 2015, Published online October 1, 2015
This paper describes the synthesis and characterization of a series of poly(2-hydroxyethyl methacrylate)
(pHEMA)-based hydrogel lenses coated with poly(ethylene glycol) (PEG) chains. A novel tri-branched
PEG-substituted hydrazide is synthesized, which imparts densely packed, covalently bound PEG layers on
hydrogels, to determine whether branching provides improved coverage of the lens surface, thereby reducing
protein adsorption. Surface modification of hydrogels with PEG was performed via amide-coupling reactions
between PEG-substituted hydrazide and the pHEMA matrix. Protein adsorption, water content, optical trans-
parency, and surface properties of the hydrogels were investigated. The hydrogels exhibited transmittance of
>90% and improved surface hydrophilicity. Notably, the amount of lysozyme adsorbed on tri-branched PEG-
coated hydrogels decreased significantly compared to the amount adsorbed onto the surface of control and lin-
ear PEG-coated hydrogels. These results provide insight into the mechanism by which PEGs reduce lysozyme
adsorption and suggest that PEG coating may offer an intriguing potential for ophthalmic biomaterials as well
as protein-resistant devices.
Keywords: Hydrogel, Poly(ethylene glycol), Protein adsorption, Contact lens
Introduction
acid (HA) and alginic acid, by constructing an IPN structure
composed of cross-linked polysaccharides and a hydrogel
matrix.23 The polysaccharide modification resulted in signif-
icantly reduced protein adsorption, compared to that observed
inthecontrolhydrogel. Sheardownandcoworkershavedevel-
oped protein-resistant hydrogels via physical adsorption
(and/or IPN construction) using HA, exhibiting reduced non-
specific protein adsorption compared to that observed in
unmodified controls.24,25 Anti-biofouling contact lenses have
been prepared by silylation of copolymers such as poly(MPC)
with the contact lenses surface hydroxyl. The modified contact
lenses showed resistance to protein adsorption and bacterial
adhesion.26 Although a considerable progress has been made
in the preparation of antifouling coatings or hydrogels using
protein-resistant polymers, only a few studies have reported
improved reduction of protein adsorption on hydrogel lenses.
This method poses a considerable number of challenges,
including the comprehensive understanding of the underlying
protein adhesion mechanisms and the development of more
environmentally friendly and effective protein-antifouling
materials for the efficient performance of contact lens.
The development of antifouling materials is of great interest
for multiple biomedical and biotechnological applications,
including medical implants, contact lenses, biosensors, drug
delivery, and catheters.1–4 Surface coating and modification
methods that utilize antifouling polymers include physical
adsorption, layer-by-layer (LbL) assembly, self-assembled
monolayers (SAMs), surface-initiated atom transfer
radical polymerization (ATRP), interpenetrating polymer net-
work (IPN), and reaction of the specific groups of
polymers with the substrate.5–11 Polyhydrophilic polymers,
including poly(ethyleneglycol) (PEG), polysaccharides, and
polyamides, and polyzwitterionic polymers, such as
2-methacryloyloxylethyl phosphorylcholine (MPC) and car-
boxybetaine methacrylate (CBMA), have been employed in
the development of bio-antifouling substrates to reduce pro-
tein adsorption and biofilm formation.12–17 In particular, the
materials used to prepare contact lenses require an elaborate
design and synthesis, with a focus on their protein-resistant
properties and biocompatibility, since the deposition of pro-
teins onto lens surfaces has been the major cause of a number
of adverse effects, including reduced vision, shortened life-
span of the lenses, bacterial keratitis, and increased
discomfort.18–22
PEG coatings among the various biocompatible polymers
have been the subject of considerable interest as a means of
reducing protein adsorption and cell adhesion on a variety
of substrates.28–30 The non-fouling properties of PEGs are pri-
marily attributed to their high chain mobility, large exclusion
volume, and steric hindrance effect.31–34 In particular, den-
dritic PEG chains have hydrophilic repeating units, conforma-
tional flexibility, and highly branched architecture, which
Protein-resistant coatings on contact lenses can be prepared
via physical/chemical adsorption and covalent grafting, using
antifouling polymers.23–27 Recently, we have functionalized
hydrogel lenses by using polysaccharides, such as hyaluronic
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KOREAN CHEMICAL SOCIETY
USA). The purity of the products was determined via thin-
layer chromatography (TLC, silica gel 60; Merck Millipore,
Darmstadt, Germany). Fourier transform infrared (FT-IR)
spectra of the hydrogels were recorded over the range
500–4000 cm−1 using a Nicolet 5700 IR spectrometer
(Thermo Electron, Beverly, MA, USA). The surface rough-
ness was investigated by atomic force microscopy (AFM)
(NX10; Park Systems, Suwon, Korea). The transmittance of
the hydrogel lenses was measured in duplicate over the wave-
length range 200–800 nm, using a Shimadzu UV-1650PC
(Shimadzu, Japan) spectrometer. Contact angles were meas-
ured using a DSA 100 (KRÜSS, Hamburg, Germany)
apparatus.
O
12
O
protein
O
NH
O
O
12
H2N
O
O
O
O
O
12
O
O
O
Amide coupling
reaction
O
NH
HN
O
p(HEMA)
hydrogel surface
Synthesis of Linear and Tri-Branched PEGs
Synthesis of Compounds 3a and 3b. Compounds 3a and 3b
were synthesized using similar procedures. A representative
example is described for compound 3a. A mixture of 4-
hydroxybenzoic acid (5.0 g, 36.2 mmol), ethanol (50 mL),
and a few drops of conc. H2SO4 was refluxed for 5 h. Excess
solvent was removed in vacuo; the reaction mixture was
poured into cold water and extracted repeatedly using methyl-
ene chloride. Combined organic extracts were washed with
10% NaHCO3, water, and brine, subsequently dried over
anhydrous MgSO4, and concentrated to obtain a white solid
(yield, 97%).
Figure 1. Schematic representation of branched PEG-functionalized
hydrogel lenses exhibiting protein adsorption resistance.
correlate with steric hindrance. These features led us to
develop surface coatings with dendritic PEG chains that
combine all of the above-mentioned properties, which might
produce hydrogel lenses with better surface wettability and
bio-antifouling property.
In this paper, novel tri-branched PEG-substituted hydra-
zides were designed and synthesized for surface modification
of poly(2-hydroxyethyl methacrylate) (pHEMA)-based
hydrogels (Figure 1). PEG chains were covalently immobi-
lized onto hydrogel surfaces by a facile one-step amide cou-
pling reaction. The effect of PEG immobilization on the
wettability, surface properties, protein adsorption, and optical
transmittance of the resultant hydrogels were investigated,
with a particular focus on the branching of PEGs compared
to the linear PEG-coated hydrogels and unmodified control.
3a:1HNMR(CDCl3, 250 MHz): δ7.95(d, 2H, Ar), 6.91(d,
2H, Ar), 4.35 (t, 2H, COOCH2), 1.38 (t, 3H, CH3).
3b: 1H NMR (CDCl3, 250 MHz): δ 7.47 (m, 2H, Ar), 4.35
(t, 2H, COOCH2), 1.54 (t, 3H, CH3).
Synthesis of Compounds 4a and 4b. Compounds 4a and 4b
were synthesized using identical procedures. A representative
example is described for compound 4a. A mixture of 3a (250
mg, 1.5 mmol), anhydrous K2CO3 (623 mg, 4.51 mmol), and
PEG- monomethylether monotosylate (MW 550, 1.37 g, 1.95
mmol) wasdissolvedinDMF(20 mL)andrefluxedfor12 h, in
the presence of argon. The reaction mixture was cooled and
distilled to remove the DMF. The resulting solution was
poured into water and extracted with methylene chloride.
The methylene chloride solution was washed with water, dried
over anhydrous MgSO4, and filtered. The crude product was
purified by column chromatography to yield 955 mg (91%)
of a viscous liquid.
Experimental
Chemicals. 2-Hydroxyethyl methacrylate (HEMA), ethylene
glycol dimethacrylate (EGDMA), methacrylic acid (MA),
polyethyleneglycol monomethylether (PEG, MW 550),
hydrazine
hydrate,
N-hydroxysuccinimide
(NHS),
4-hydroxybenzoic acid, gallic acid, 1-ethyl-3-(3-dimethyla-
minopropyl)-carbodiimide (EDC), lysozyme (chicken egg
lysozyme), dimethylformamide (DMF), tetrahydrofuran
(THF), and albumin (bovine serum albumin) were
purchased from Sigma Aldrich (St. Louis, MO, USA).
N-vinylpyrrolidone (NVP) and azobisisobutyronitrile
(AIBN) were purchased from Junsei (Tokyo, Japan). Unless
otherwise indicated, all starting materials were obtained from
commercial suppliers (Sigma Aldrich, Acros Organics (Geel,
Belgium), TCI (Tokyo, Japan), etc.) All atmosphere-sensitive
reactions were performed in the presence of nitrogen. UV light
and iodine vapors were used for visualization.
4a:1HNMR(CDCl3, 250 MHz): δ7.95(d, 2H, Ar), 6.88(d,
2H, Ar), 4.31 (q, 2H, COOCH2), 4.11 (t, 2H, Ar-OCH2), 3.67
(t, 2H, Ar-OCH2CH2), 3.47–3.63 (m, 44H, OCH2), 3.34 (s,
3H, OCH3) 1.32 (t, 3H, CH3).
4b: 1H NMR (CDCl3, 250 MHz): δ 7.26 (s, 2H, Ar), 4.32 (q,
2H, COOCH2), 4.15 (m, 6H, Ar-OCH2), 3.82 (m, 6H, Ar-
OCH2CH2), 3.45–3.75 (m, 132H, OCH2), 3.34 (s, 9H,
OCH3) 1.34 (t, 3H, CH3).
Synthesis of Compounds 1 and 2. Compounds 1 and 2 were
synthesized using similar procedures. A representative exam-
ple is described for compound 1. Compound 4a (500 mg,
0.714 mmol) and hydrazine monohydrate (178 mg, 3.57
mmol) were dissolved in MeOH (10 mL) and THF (3 mL).
The reaction mixture was stirred at 70 ꢀC for 12 h, cooled to
Equipment. 1H-NMR spectra were recorded from CDCl3
solutions on a Bruker AM 250 spectrometer (Billerica, MA,
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Development of Hydrogel Lenses with Surface-immobilized PEG Layers
KOREAN CHEMICAL SOCIETY
room temperature, and the organic solvents were removed
under reduced pressure. The mixture was dissolved in methyl-
ene chloride and washed with H2O. The organic layer was
dried over anhydrous MgSO4, and the solvent was evaporated
to obtain the crude product, which was purified by column
chromatography. The chromatography procedure utilized
8% MeOH in ethyl acetate as the eluent in order to obtain
the pure product as a viscous liquid (450 mg, 92%).
mL of the artificial tear solution and were incubated at a tem-
perature of 37 ꢀC under constant rotation for 12 h. After the
first incubation period, the lenses were rinsed with PBS to
remove any unbound protein on the lens surface. The lenses
were then placed in an extraction solvent containing acetoni-
trile/0.2 wt % trifluoroacetic acid and were incubated in the
dark at room temperature for 24 h. The concentration of pro-
teins extracted from the hydrogels was quantified by reverse-
phase high-performance liquid chromatography (RP-HPLC).
The HPLC system (Shimadzu, kyoto, Japan) consisted of an
LC-10AVP pump, an LC-20AD autosampler, and an SPD-
10A UV detector. One hundred microliters of the extracted
lysozyme solution or 10 μL of the extracted albumin was
mixed with 900 or 990 μL of the mobile phase solution,
respectively; 20 μL of this mixture was injected into a C18
column (LUNA-C18, 4.6 × 150 mm, 5 μm; Phenomenex,
Torrance, CA, USA). The proteins were eluted with an iso-
cratic mixture of 50% acetonitrile containing 0.1% of trifluor-
oacetic acid and 50% water. The run time and flow rate were
set to 4.5 min and 1.0 mL/min, respectively, and the samples
were detected at 220 nm. Data are given as the mean Æ SD of
three measurements.
1: 1H NMR (CDCl3, 250 MHz): δ 7.92 (d, 2H, Ar), 6.92 (d,
2H, Ar), 4.15 (m, 2H, Ar-OCH2), 3.87 (t, 2H, Ar-OCH2CH2),
3.49–3.73 (m, 44H, OCH2), 3.36 (s, 3H, OCH3).
2: 1H NMR (CDCl3, 250 MHz): δ 7.13 (s, 2H, Ar), 4.19 (m,
6H, Ar-OCH2), 3.83 (m, 6H, Ar-OCH2CH2), 3.47–3.77 (m,
132H, OCH2), 3.37 (s, 9H, OCH3).
Preparation of pHEMA Hydrogels Functionalized with
PEG. HEMA monomer was purified by vacuum distillation
prior to polymerization. EGDMA (0.05 g), NVP (1.20 g), MA
(0.10 g), and AIBN (0.04 g) were dissolved in HEMA (8.65
g). The standard monomer formulations for the three hydro-
gels used in this study are shown in Table 1. The monomer
solution was injected into 0.08-mm-thick polypropylene con-
tact lens molds. The molds were then placed in an oven and
heated at 100 ꢀC for 5 h. After polymerization, the samples
were removed from the molds and cooled in water for 2 days
to remove any unreacted monomers and initiators in the sam-
ples. ThepHEMAsampleswerethendriedina24-well plateat
40 ꢀC overnight. The hydrogels were prepared by swelling
each driedpHEMAsample indistilled water for3daysatroom
temperature. In order to functionalize the surface of hydrogels
with PEGs, they were immersed in a 75% ethanol (7.5 mL)/
25% water (2.5 mL) solution containing PEG-substituted
hydrazides (0.2 mmol), EDC (0.3 mmol), and NHS (0.3
mmol). The mixture solutions were shaken for 24 h at room
temperature to induce amide-coupling reactions between the
amino groups of hydrazides and carboxylic groups of
MA. The hydrogels were washed with water and ethanol
and subsequently immersed in water for 72 h to remove any
unreacted PEGs, EDC, and NHS prior to characterization.
Quantitation of Protein Deposition onto Hydrogel Lenses.
An artificial tear solution, containing 3.88 g/L of bovineserum
albumin and 1.20 g/L of chicken egg-white lysozyme dis-
solved in phosphate buffered saline (PBS, pH 7.4), was pre-
pared as previously reported.35 It should be noted that
human and chicken lysozymes share a high degree of similar-
ity in their primary and tertiary structures.36 Six lenses of each
lens type were incubated for 12 h. The lenses were placed in 5
Results and Discussion
Synthesis and Characterization. Two series of PEG-
substituted benzohydrazides 1 and 2 were prepared as per
the synthetic strategies detailed in Figure 2. PEG synthesis
was initiated with ethyl-4-hydroxy benzoate (3a) and ethyl
3,4,5-trihydroxy benzoate (3b), which underwent Williamson
ether reactions with the appropriate PEG-monomethylether
monotosylate (MW 550) by using anhydrous potassium car-
bonate, to form PEG-substituted benzoates 4a and 4b. The
subsequent amide-coupling reactions of the benzoates with
hydrazine monohydrate produced linear and tri-branched
PEG-substituted hydrazides, respectively. The unmodified
hydrogel (H) contains 1 wt % MA, which is conjugated with
PEGs through the amide-coupling reactions occurring
between PEG-substituted hydrazides and carboxylic acids
of MA units. The hydrogels were functionalized with linear
PEG 1 and tri-branched PEG 2, yielding P1 and P2, respec-
tively. The hydrogels modified with PEGs were investigated
by FT-IR spectroscopy (Figure 3). A strong peak, assigned
to the C O stretching band from the HEMA ester group,
was observed at 1710 cm−1 for all hydrogels. The
Table 1. Characteristics of hydrogels functionalized with PEG.
Composition ratio of
monomers (wt %)
Coated
PEG
Transmittance
Water
content (%)
Water contact
angle (ꢀ)
Root mean square
roughness (nm)
Hydrogels HEMA NVP MA EDGMA
(%)
H
P1
P2
86.5
86.5
86.5
12
12
12
1
1
1
0.5
0.5
0.5
—
1
2
91
90
90
44
46
46
65.2
53.4
43.0
3.56
6.21
7.13
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O
i
ii
iii
O
O
O
O
H
O
H
OOC
H
O
O
O
12
12
O
97 %
91 %
92 %
O
H2N NH
3a
4a
1
O
O
O
O
12
12
H
H
O
H
H
O
O
O
O
O
O
O
i
ii
iii
O
O
O
O
O
H
O
H
OOC
H
O
O
O
12
12
98 %
82 %
91 %
H2N NH
O
O
12
12
3b
4b
2
Figure 2. Synthetic routes for amine-functionalized PEG 1 and 2. Reagents and conditions: (i) ethanol, H2SO4, reflux; (ii) poly(ethylene glycol)
monomethylethermonotosylate, K2CO3, DMF, 80 ꢀC;(iii)hydrazinehydrate, MeOH/THF, 70 ꢀC0.5 wt%ofAIBN(initiator)wereaddedtothe
total monomers and crosslinking mixtures prior to polymerization.
(a)
(a)
(b)
nm
160
120
80
(b)
(c)
40
3000
2000
cm-1
1000
0
Figure 4. AFM images of dried (a) H and (b) P2. Scale bar is 1 μm.
Figure 3. FT-IR spectra of (a) H, (b) P1, and (c) P2.
functionalization of the hydrogels with PEGs did not show the
expected absorption peaks of aliphatic ether (C O C)
stretching at 1120 cm−1 in the PEGs and an amide band I peak
at 1650 cm−1 because of their overlap with the absorption
peaks of ester and amine units from HEMA and NVP.
The optical analysis revealed a transparency >90% for both
the control and PEG-coated hydrogels, indicating that surface
immobilizationwithPEGshadnoeffect onthetransparencyof
hydrogels (Table 1). The PEG layers coated on the hydrogels
were characterized by tapping-mode atomic force microscopy
(AFM) to determine whether they resulted in changes to the
surface roughness. Figure 4 shows that the surfaces of PEG-
modified hydrogels are rougher than those of the unmodified
hydrogels, as indicated by the root mean square (RMS) rough-
ness values presented inTable1. While the AFM images of the
unmodified surfaces of H appeared fairly smooth, with small
and equally distributed narrow features, the PEG-coated
hydrogels P1andP2showedunevenlydistributed broaderfea-
tures. This may be attributed to heterogeneous PEG coverage,
resulting in the formation of a rougher surface.
compared to the unmodified control, as the amount of attached
PEGs was too small. The surface contact angle by water is an
important factor for evaluating surface hydrophilicity. As
shown in Table 1 and Figure 5, the presence of hydrated
PEG chains decreased the contact angle of the hydrogels,
implying increased surface wettability. The contact angles
of P1 and P2 were observed to be 53.4ꢀ and 43.0ꢀ, respec-
tively, which were lower than the observed value of 65.2ꢀ
for H. Notably, the contact angle of P2 decreased by ~20%
compared tothat of P1, suggesting that tri-branched PEGspro-
vide higher surface hydrophilicity compared to the linear
PEGs. This result was attributed to surface enrichment with
branched PEGs, which covered the hydrogel surfaces with
greater efficiency, compared to that observed with the linear
PEGs. High-water-content lens materials are commonly
obtained by the copolymerization of moderately hydrophilic
HEMA with highly hydrophilic ionic monomers such as
methacrylic acid (MA). Because of its ionic functionality,
MA is used toincrease the water content in the hydrogel. How-
ever, the use of ionic monomers increases the protein adsorp-
tion of hydrogels, while the branched PEG chains increase
Water Content and Hydrophilicity of Hydrogels. The PEG
coating did not increase the water content of hydrogels
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Development of Hydrogel Lenses with Surface-immobilized PEG Layers
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surface hydrophilicity without the use of ionic units, demon-
strating the potential applicability of these hydrogels in the
contact lens industry.
vifilcon A.37 According to some previously reported studies,
lysozyme is extensively taken up by the hydrogel containing
MA, implying that the H containing 1% MA may have attrac-
tive interactions with lysozyme.38,39 It appears that the PEG
immobilization between the carboxylic acids of H and the
amine groups of PEG-substituted hydrazides facilitates the
formation of amide bonds, which may result in a nearly neutral
hydrogel surface. In addition, the presence of PEG layers
reduces lysozyme adsorption, since their neutral hydrophilic
characteristics repel the negatively charged lysozymes and
prevent interactions with the hydrophobic domain that can
cause lysozyme denaturation and subsequent surface accumu-
lation. Notably, tri-branched PEG modification showed a bet-
ter ability to repel lysozyme than the linear PEG treatment. It
has been reported that the antifouling ability of PEG chains
depends on diverse parameters, including the PEG grafting
density, chain length, polymer architecture, and chain mobil-
ity. A comparison of the structural differences between the lin-
earandbranchedPEGs revealed theimportanceoftheeffect of
the PEG surface density, since a low surface density may not
provide significant steric exclusion, while a high surface den-
sity may not allow enough mobility to the PEG chains. The
surface hydration and steric repulsion associated with hydro-
gel surface coverage of branched PEG work together to impart
greaterefficiency tothelysozyme-repellingpropertyofhydro-
gel P2 prepared from tri-branchedPEG, compared to the linear
PEG hydrogel.
Protein Adsorption to Hydrogel Lenses. Lysozyme adsorp-
tion onto the synthesized hydrogels is shown in Figure 6. The
presence of PEG layers on the hydrogel surface was highly
effective in preventing the adsorption of the lysozyme. The
amounts of lysozyme adsorbed onto the PEG-modified hydro-
gels P1 and P2 were observed to be 171.74 and 83.13 μg/lens,
respectively, indicative of 36 and 69% reduction, compared to
267.52 μg/lens observed for unmodified hydrogel
H
(Figure 6). The amount of adsorbed lysozyme on P2 exhibited
52% reduction approximately, compared to that of P1, indicat-
ing that the protein resistance of the branched PEG is much
better than that of the linear PEG. This result can be rationa-
lized by considering the surface charge of the lysozyme and
the steric hindrance effect of PEG. The lysozyme with an iso-
electric point (pI) of 10.7 displayed a positively charged sur-
face at physiological pH; therefore, its adsorption onto
negatively charged substrates is electrostatically favorable.
The ionic functionality of the MA unit in an aqueous environ-
ment increases the water content and surface hydrophilicity of
the hydrogel. Lysozyme may be electrostatically attracted to
the carboxylate anions of the MA units, which are highly
hydrophilic ionic monomers that are used often in the manu-
facture of soft contact lenses, such as etafilcon A and
The amounts of albumin adsorbed onto the H, P1, and P2
surfaces were approximately 19.78, 17.83, and 16.78 μg/lens,
indicating that PEG treatment reduces albumin adsorption
(Figure 7). Considering the pI of albumin (4.7), the
hydrogel H, containingcarboxylateanions, mayrepelalbumin
with a negatively charged surface at pH 7.4. The PEG-coated
surfaces of hydrogels P1 and P2 may be sterically inaccessible
to albumin. Specifically, the branched PEG layer of P2 is more
effective in preventing the adsorption of albumin. Therefore,
the albumin-resisting ability is related to the PEG modification
of hydrogels containing MA units.
(a)
(b)
Figure 5. Photographs of contact angles with water. (a) H and (b) P2.
25
20
15
10
5
300
250
200
150
100
50
0
0
H
P1
P2
H
P1
P2
Figure 6. Graph depicting the amount of adsorbed lysozyme on the
pHEMA lens and PEG-functionalized hydrogel lenses. Each value is
expressed as mean Æ standard deviation, n = 3.
Figure 7. Graph depicting the amount of adsorbed albumin on the
pHEMA lens and PEG-functionalized hydrogel lenses (μg/lens).
Each value is expressed as mean Æ standard deviation, n = 3.
Bull. Korean Chem. Soc. 2015, Vol. 36, 2682–2687
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29, 780.
Novel tri-branched PEG-substituted benzohydrazides were
synthesized and used as building blocks for the preparation
of protein-resistant hydrogels via surface modifications. The
PEG-modified hydrogels exhibited high transparency and
improved surface hydrophilicity compared to the untreated
hydrogels. The PEG coating was proven to successfully
reduce the adsorption of lysozyme onto the hydrogel surfaces
because of their bioinert and highly hydrophilic nature. Nota-
bly, the tri-branched PEG treatment reduced the lysozyme
adsorption with greater efficiency compared to linear PEGs.
This result is attributed to the characteristic structural features
of branched PEGs, which combine a highly flexible polyether
with hydrophilic surface groups and a highly branched archi-
tecture, resulting in a strong steric hindrance, which repels the
approaching lysozyme efficiently. The preparation of hydro-
gels with a PEG-immobilized surface may be a new method
for the development of ophthalmic biomaterials as well as
protein-resistant devices.
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Acknowledgments. This study was supported by research
funds provided by Chosun University in 2013.
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