Special Issue
Revolutionary advances in 2-methacryloyloxyethyl phosphorylcholine
polymers as biomaterials
Kazuhiko Ishihara
Department of Materials Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan
Received 6 June 2018; accepted 24 January 2019
Published online 13 February 2019 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/jbm.a.36635
Abstract: In the last 40 years, many strategies to fabricate bio-
compatible and antithrombogenic polymers have been pro-
posed, especially in Japan. The development of one such
polymers composed of 2-methacryloyloxyethyl phosphoryl-
choline unit, is described in this review, with specific exam-
ples of use in biomedical devices. These polymers are
typically incorporated into other materials to effectively pre-
vent unfavorable biological responses and reactions. For
example, the polymers suppress protein adsorption and cell
adhesion to materials in contact with plasma or whole blood,
even in the absence of anticoagulant. These properties are
How to cite this article: Ishihara K. 2019. Revolutionary advances in 2-methacryloyloxyethyl phosphorylcholine polymers as bio-
materials. J Biomed Mater Res Part A 2019:107A:933–943.
DEVELOPMENTS OF ANTITHROMBOGENIC POLYMERS IN
JAPAN IN THE LAST 40 YEARS
Many medical devices, including implantable cardiovascular
artificial organs, come into contact with blood, and thrombus
formation at such devices is a critical issue. Accordingly, the
development of antithrombogenic materials has been one of
the most active areas in biomedical, medical, and pharma-
ceutical research, starting in the 1960s. By the 1970s, sev-
eral concepts had been proposed,1–9 including grafting of
water-soluble polymers to surfaces, deposition of microdo-
mains using block-type segmented polymers, controlling sur-
face charge using polyelectrolytes, and hybridization with
biologically active molecules. For instance, heparinization of
surfaces was found to reliably delay blood coagulation, and
thus enabled deployment of temporary-use medical devices
such as catheters and oxygenators.9
Of note, members of the Japanese Society for Biomaterials
were pivotal to the development and testing of antithrombo-
genic materials, especially polymers. One project, “Design of
multiple-phase biomedical materials,” was active from 1982
to 1984 with support from the Ministry of Education, Japan.
This project brought together many members of the Japanese
Correspondence to: K. Ishihara; e-mail: ishihara@mpc.t.u-tokyo.ac.jp
Contract grant sponsor: Japan Science and Technology Agency
© 2019 WILEY PERIODICALS, INC.
due to the extreme hydrophilicity and electrically neutral
nature of the polymers, as well as to the ability of phosphoryl-
choline to induce bulk-like behavior in surrounding waters.
Accordingly, these polymers have been used worldwide to
modify the surfaces and improve the overall biocompatibility
of such medical devices as long-term implantable artificial
organs. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A:
107A: 933–943, 2019.
Key Words: antithrombogenicity, phosphorylcholine group,
surface modification, protein adsorption, cell adhesion
Society for Biomaterials, and produced a variety of antithrom-
bogenic polymers (Fig. 1), including hydrophobic–hydrophilic
segmented block-type polymers synthesized by Okano,10,11
polyion complexes derived by Kataoka from polystyrene,12
and amorphous–crystalline surfaces fabricated by Yui.13 These
polymers suppress platelet adhesion and activation on struc-
turally heterogeneous, neutral, or totally hydrophilic sur-
faces, as measured in vitro by flowing whole blood and
platelets through column packed with the polymer-coated
microspheres.7 Subsequently, polyion complexes and
amorphous–crystalline surfaces were applied to temporary-
use medical devices such as cell separation filters and cannu-
las, respectively. Poly(2-hydroxyethyl methacrylate [HEMA]-
block-styrene) was also applied to a small-diameter vascular
prosthesis,10,14 which, however, was not usable as implant
despite good patency in animal models over 3 years.
Drawing inspiration from an article which has been pub-
lished in Journal of Biomedical Materials Research in 1976,15
in which Noishiki reported that poly(ethylene terephthalate)
(Dacron) vascular prostheses coated with phospholipids exhibit
long-term patency in animals, Nakabayashi of Tokyo Medical
and Dental University synthesized 2-methacryloyloxyethyl
933
FIGURE 1. Molecular design concepts for antithrombogenic polymers proposed during last 40 years.

phosphorylcholine (MPC) and its polymers, which were
described in 1978.16 At that time, yields of the MPC were
poor from early synthetic attempts, which prevented suffi-
cient testing of the antithrombogenicity. After that, an effi-
cient synthetic route has since been developed, and different
types of MPC polymers have been obtained and evaluated
actively for antithrombogenicity and biocompatibility.17–20 In
this review, the properties of MPC polymer-coated surfaces
were summarized, as well as the biological reactions that
occur at such surfaces. Some examples of MPC polymers use
in clinical devices are also described.
PREPARATION OF MPC POLYMERS
An elegant synthetic procedure of MPC with well-defined
reaction conditions was first developed in 1987, and then
reported in 1990 (Fig. 2).21 This method was licensed to the
Japanese chemical company, NOF Corp. Ltd., with support
from the Japan Science and Technology Agency (JST). An
industrial-scale facility was set up in 1994 and completed in
1999. During this period, small modifications were made to
the synthetic procedure to increase the yield to 80% and
achieve purity >98.0%, thus enabling MPC use in bio-related
industry and medical industry. This plant continues to

FIGURE 2. Development process of MPC and its polymers.

934 ISHIHARA REVOLUTIONARY ADVANCES IN 2-METHACRYLOYLOXYETHYL PHOSPHORYLCHOLINE POLYMERS


FIGURE 3. Control of molecular structure of the MPC polymers.
operate today, producing almost 10 tons of MPC each year.22
A worldwide distribution network for MPC as a reagent
means that researchers can obtain it easily. This opened up
the field of MPC polymer science for application in the bio-
medical engineering and clinical medicine fields after high
purity MPC was successfully obtained.
Copolymerization of MPC with other vinyl compounds
was also systematically investigated by conventional23 or
advanced living radical polymerization24–27 into various archi-
tectures, such as block-type and graft-type copolymers.24–29
Recently, surface-initiated living radical polymerization of
MPC was also demonstrated to form polymer brushes with
unique properties arising from the high density of polymer
graft chains.30–32 Typically, MPC copolymerizes efficiently
with styrene and with various alkyl methacrylates such as n-
butyl methacrylate (BMA), n-hexyl methacrylate, n-dodecyl
methacrylate (DMA), or n-stearyl methacrylate, resulting in
polymers with statistically random sequence. Naturally, the
subunit composition of the resulting polymer can be altered
by simply changing the ratio of monomers added. In addition,
the solubility of these polymers depends on the proportion of
MPC units incorporated, the hydrophobicity of the alkyl meth-
acrylate, and the molecular weight of the polymer (Fig. 3). It
is noted that MPC polymers are soluble in water and alcohol,
but not in 60–92 vol % aqueous ethanol. Poly(MPC-co-BMA)
(PMB) is the most valuable MPC polymer, of which three
types with different MPC unit compositions and molecular
weights are commercially available today.22,23 One is the
water-soluble PMB80, which contains 80 mol % MPC units
and is used as a moisture trap in contact lenses and as a com-
ponent in cosmetics. The other is the water-insoluble PMB30,
which is used as coating in medical devices. Water insolubility
and chemical stability in physiological conditions (pH 7.4,
ionic strength 150 mM) and during sterilization are achieved
by controlling the polymer molecular weight (>5 × 105) and
the MPC unit content (about 30 mol %). This polymer is reg-
istered in the Device Master File of the US Food and Drug
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A | MAY 2019 VOL 107A, ISSUE 5
SPECIAL ISSUE
Administration as Lipidure-CM5206 (NOF Corp., Japan). The
molecular weight is important factor to determine the solubil-
ity of the PMB30 in water. That is, the low molecular weight
PMB30 named PUREBRIGHT (NOF), which has below 5 × 104
as molecular weight, can dissolve in aqueous medium and
form polymer aggregate through hydrophobic interaction.33,34
So, it can be applied to the solubilizer for the poorly water-
soluble bioactive compounds by the polymer aggregate.
SURFACE PROPERTIES OF MPC POLYMERS
As MPC polymers are soluble in alcohol, substrates such as
general metals, ceramics, and plastics can be coated by sim-
ple solvent evaporation. In the case of the water-insoluble
PMB30, the hydrophilic phosphorylcholine groups are large
enough so that the substrate is covered entirely, with static
water contact angle 30  at equilibrium. However, a large
hysteresis in the contact angle is observed when the surface
is immersed in and withdrawn from water,35 suggesting high
mobility of the polymer chain at the air/water interface, as
well as a change in the orientation of phosphorylcholine
groups. Consequently, equilibration is required to establish
surface hydrophilicity, although this is quickly achieved since
PMB30 is deposited at a thickness of only about 100 nm.
Importantly, the zeta potential of PMB30 is nearly zero, since
internal salt bridges are formed between phosphate anions
and trimethylammonium cations in phosphorylcholine.
Accordingly, many substrates have nearly zero surface zeta
potential after coating with PMB30,17,22,36 even metal and
glass, which typically have large negative zeta potential
before coating. The lack of electrical charges may also reduce
interactions with biomolecules.37 Coating with MPC poly-
mers also dramatically enhances lubricity in aqueous
medium that depends on hydrophilicity.38–40 The increase in
lubricity is due to the low viscosity of the polymer, which, in
turn, arises from its structural properties, and from weak
interactions with surrounding waters.
935
FIGURE 4. Hydration state of the MPC polymer at aqueous interface.
Interfacial phenomena at MPC polymers are mostly attrib-
utable to waters surrounding phosphorylcholine groups
(Fig. 4).41 As a rule, water molecules prefer to interact with
each other by strong hydrogen bonding, and thereby form
clusters. Accordingly, ions and other hydrogen bonding part-
ners disrupt such clusters by directly interacting with water
molecules. In contrast, hydrophobic groups tend to reinforce
such clusters, since interactions between hydrophobic groups
and water molecules consist mostly of van der Waals forces,
which are weaker than hydrogen bonds. Using Raman spec-
troscopy, it has been revealed that the poly(MPC) aqueous
solution and PMB30-coated surface show less destroying the
hydrogen bonding between water molecules in the bulk water
phase.42,43 It is due to weak interaction of PMB30 with water
molecules even the phosphorylcholine group takes hydro-
philic nature. In MPC polymers, the three hydrophobic methyl
groups bonded to nitrogen in phosphorylcholine are surface
exposed because the phosphate anion and trimethylammo-
nium cation are closely linked by electrostatics. Accordingly,
the methyl groups induce hydrophobic hydration, in which
water molecules aggregate into bulk-like structures.44,45 In
other words, MPC polymers are covered with a layer of bulk-
like water.46,47 Thus, protein molecules do not accept signifi-
cant molecular interaction such as electrostatic interaction
and hydrophobic interaction on the surface. Also, water move-
ment at the interface is quick as that same as that in aqueous
medium, so that, protein molecules attached on the surface
can detach from the surface quickly and easily. As the results,
amount of protein adsorbed tightly on the surface is
extremely small on the PMB30 surface.
INTERACTION WITH BLOOD COMPONENTS
When hydrophilic polymer-modified substrates come into
contact with blood and body fluids, surfaces are wetted with
936 ISHIHARA REVOLUTIONARY ADVANCES IN 2-METHACRYLOYLOXYETHYL PHOSPHORYLCHOLINE POLYMERS
aqueous medium containing ions and eventually covered
with proteins and cells. Protein adsorption to surfaces has
been extensively studied, including in systems consisting of
a buffer supplemented with a single protein, and was found
to strongly influence the subsequent adhesion of cells.48 The
amount and orientation of adsorbed proteins are essential to
cell adhesion, as is the protein that accumulates at the top of
what could be multiple distinct protein layers, since this pro-
tein will be in direct contact with environment.
In cooperation with Anderson and Ziats at Case Western
Reserve University, eight human plasma proteins were found
to adsorb to glass and poly(BMA), as described in Journal of
Biomedical Materials Research in 1991.49 These proteins
were identified by sandwich-type immunoassay, which
detects only the proteins at the top layer, and include the
major plasma proteins albumin, γ-globulin, and fibrinogen.
The minor plasma proteins high-molecular-weight kininogen,
complement protein C5, fibronectin, and coagulation factors
XII (Hageman factor XII) and VIII (von Willebrand factor)
were also detected, but at lower concentrations than the
major proteins. Of note, these proteins are essential to blood
coagulation and cell adhesion. Importantly, coating with
PMB significantly reduced the adsorption of these proteins,
regardless of plasma concentration and contact time. These
results were confirmed by immunoassays with fibrinogen
antibodies conjugated to gold colloids, which accumulated
strongly on glass and poly(BMA), but accumulated to a far
lower extent on PMB-coated devices.
In general, MPC polymers effectively inhibit the adhesion
of many cell types, including platelets and white blood cells,
by altering the composition, chemical structure, and architec-
ture of surfaces. Platelet adhesion, morphology, and activa-
tion have been directly observed by using platelet-rich-
plasma and whole blood.23,24,50–58 Although MPC unit con-
tent was found to be critical, 30 mol % MPC unit was
 SPECIAL ISSUE

FIGURE 5. Effects of MPC polymer modification on the surface antithrombogenicity and biocompatibility. Protein adsorption was evaluated atomic
force microscope after contact with protein solution for 90 min. Cell adhesion was evaluated by culturing Cos 7 kidney cells for 24 h. Thrombus forma-
tion was examined using small diameter polyester vascular grafts coated with SPU and SPU/MPC polymer blend. The vascular grafts were implanted
into rabbit artery for 90 min in the SPU case and 1 month in the SPU/MPC polymer case. Tissue response was observed using SPU and SPU/MPC
polymer membranes after implantation subcutaneously for 2 weeks. Tissues surrounding the specimen are stained by hematoxylin–eosin method.

sufficient to significantly suppress platelet adhesion to and
activation on microspheres under flow, and also even after
1–3 h of static contact. Short-term contact with human
whole blood also indicated effective suppression of blood
coagulation on PMB30, even in the absence of anticoagu-
lants.51 Cells flowed on PMB also do not adhere, but instead
survive for 3 days as floating aggregates (Fig. 5). Similar
behaviors were observed with macrophages,53 HeLa cells,
human umbilical vein endothelial cells, and embryonic stem
cells.58 Collectively, these observations indicate that MPC
polymer is an excellent inhibitor of cell adhesion and activa-
tion as a result of suppressed protein adsorption.
SURFACE MODIFICATION OF BIOMATERIALS WITH THE MPC
POLYMERS
MPC polymers are themselves mechanically unsuitable as
medical devices. Therefore, these polymers have been used
in the last 25 years only to modify the surfaces of conven-
tional materials used in medical devices. These are summa-
rized in Table I. The representative MPC polymer, PMB is
applied widely. Surface modification using the PMB is
achieved conveniently by solvent evaporation, and the thick-
ness of the coat is controlled via the concentration of the
polymer, for example, a coat of 20–100 nm is deposited at
polymer concentrations of 0.1–1.0 wt %. However, this pro-
cess is unsuitable for coating polyolefins, which are not suffi-
ciently wetted by ethanol, the solvent typically used to
dissolve MPC polymers. Thus, MPC polymers variants with
enhanced solubility in less polar solvents such as
tetrahydrofuran are useful in this case. These include
poly(MPC-co-DMA) (PMD) and poly(MPC-co-2-ethylhexyl
methacrylate), which are soluble in tetrahydrofuran at
0.5 wt %. These polymers are also more adhesive and less
easily stripped off due to relatively lower glass-transition
temperatures.
Since some conventional polymers are already used in
medical devices, blending with MPC polymers during device
fabrication is a straightforward alternative to coating after
the fact. Physical incorporation of MPC polymers into the
base polymer may enhance the long-term stability of the sur-
face. Accordingly, blending of MPC polymers was attempted to
polyethylene [PE]),68–70 polysulfone (PSf),75–77 segmented
polyurethane (SPU),28,29,53,78–82 and polydimethylsiloxane.82–85
Notably, no significant phase separation was observed,
although microdomains may have formed. A blend of PSf and
MPC polymer was molded into a hollow fiber membrane for
use in blood purification devices.76 This hollow fiber was fabri-
cated on a double-nozzle system with water as inner liquid
phase. Consequently, hydrophilic nature of the MPC polymers
induced migration and accumulation at the water contact
phase, resulting in a dense inner surface with concentrated
MPC unit. This layer is encased mainly by PSf, to which the
hydrophobic elements of MPC polymer are also anchored.
Thus, the final device has asymmetric structure, and has excel-
lent mechanical properties and blood compatibility, in compar-
ison to conventional PSf hollow fibers, which are fabricated
with poly(vinylpyrrolidone) (PVPy) as pore forming reagent.
However, PVPy was, in the end, incorporated evenly across
the device, and its hydration degraded the mechanical

JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A | MAY 2019 VOL 107A, ISSUE 5 937
TABLE I. Conventional Medical Substrates Modified with the MPC Polymers

Materials Method Functions References

PMMA, acrylic polymer Coating, reaction Reduced protein adsorption and bacteria 59–63
adhesion
PET Coating, grafting Reduced protein adsorption 35,64
Polyurethane Coating Antithrombogenicity, improved lubricity 39,65
PVC Coating Antibiofouling 66
PP Coating Reduced protein adsorption 23,67
PE Blending Cell adhesion resistance 68–70
UHMWPE Grafting Improved lubrication 71,72
PTFE Grafting Antithrombogenicity 73,74
PSf Blending, coating Antithrombogenicity 75–77
SPU Coating, blending Antithrombogenicity 28,29,53,78–82
PDMS Grafting, coating, blending Reduced protein adsorption 83–86
Cellulose Grafting, reacting, coating Reduced protein adsorption, 87,88
antithrombogenicity
PLA, PLGA Blending, coating Reduced protein adsorption 89,90
PEEK Grafting Improved lubrication, antithrombogenicity 91–97
Co-Cr alloy Reacting Improved lubrication 40,98,99
Ti alloy Coating, reacting Reduced protein adsorption, antibiofouling 100–105
SUS Coating Suppression of bacteria adhesion and biofilm 106
formation
HAp Coating Antibiofouling 107
DLC Coating antithrombogenicity 108
Abbreviations of materials are DLC; diamond-like carbon, HAp; hydroxyapatite, PET; poly(ethylene terephthalate), PDMS; polydimethylsiloxane,
PE; polyethylene, PEEK: poly(ether ether ketone), PLA; poly(lactic acid), PLGA; poly(lactic acid-co-glycolic acid), PP; polypropylene, PSf; polysul-
fone, PTFE; polytetrafluoroethylene, PVA; poly(vinyl chloride), SPU; segmented polyurethane, SUS; stainless steel, UHMWPE; ultra-high-
molecular weight polyethylene.

properties of the hollow fiber. In addition, conventional PSf
hollow fibers became occluded within 1 h of exposure to
whole blood circulating ex vivo through a hemodialyzer. On
the other hand, PSf/MPC polymer hybrid hollow fibers did not
induce blood coagulation, even in the absence of anticoagulant.
The water-soluble and amphiphilic PMB80 is an especially
convenient modifier of PSf hollow fibers during follow fiber
fabrication process,77 since it is soluble in aqueous media, and
is adsorbed and fixed spontaneously as described to blood-
facing surfaces. This device also does not induce coagulation in
blood circulating ex vivo for more than 1 h without anticoagu-
lant treatment.
Some MPC polymers have also been blended with SPU,
such as Tecoflex.28,29,78–81 The MPC polymers are dissolved
to a mixture of chloroform and ethanol, because the SPU is
soluble in the former solvent while the MPC polymer is solu-
ble in the latter solvent. Upon casting on glass, the SPU is
deposited more quickly and forming a thin membrane at the
air contacting surface by faster evaporation of chloroform
than that of ethanol. Subsequently, the MPC polymer accu-
mulates on glass facing surface as ethanol evaporates.
Importantly, addition of only 5 wt % MPC polymer against
SPU is sufficient to inhibit coagulation at the resulting sur-
face, as evaluated in vitro using platelet-rich plasma and
whole blood. To evaluate in vivo performance,80 tubings with
diameter 2 mm, which are prepared by polyester microfi-
bers, were coated with the SPU/MPC polymer blend, and
implanted as vascular prostheses in a rabbit artery (Fig. 5).
These prostheses remained functional and patent 1 month after
implantation. In contrast, polyester tubings coated with pure
SPU completely occluded within 90 min after implantation.
These findings have made clear conclusions that the MPC poly-
mers can prevent unfavorable biological responses and biofoul-
ing, and improve lubrication at the surface.
APPLICATION OF MPC POLYMERS IN MEDICAL DEVICES
Cardiovascular devices
As shown in Table II, many medical devices using the MPC
polymer have been approved and clinically used. These have
been summarized well in the book chapters.109–111 Coronary
guide wires developed in the United Kingdom were the first
medical devices to be coated with MPC polymers, specifically
PMD.112 The coat significantly suppresses thrombogenesis,
which occurs at 48% of uncoated guide wires. MPC polymer
coating has also been investigated in other cardiovascular
devices, including left ventricular assist devices (LVADs),
extracorporeal circuits, vascular grafts, and coronary stents.
Of these, BiodivYsio coronary stents stably coated with
crosslinked MPC polymers have been approved in the United
States and the European Union, specifically those designed
for small vessels around 2.0 mm in diameter. The coat con-
sists of poly(MPC-co-DMA-co-2-hydroxypropyl methacrylate
(HPMA)-co-3-(trimethoxysilyl)propyl methacrylate [TSMA])
self-crosslinked by reaction of HPMA unit with TSMA
unit.113,114 The performance of the MPC polymer coating on
the stent application has been summarized in a literature.115
To avoid eventual occlusion by abnormal growth of the
blood vessel, stents are coated with 1 μm thick MPC poly-
mers infused with drugs, which are then slowly released.
For example, an MPC polymer-coated stent that delivers an
anti-inflammatory steroid suppresses inflammation and
neointimal hyperplasia in animal models.116 Based on such

938 ISHIHARA REVOLUTIONARY ADVANCES IN 2-METHACRYLOYLOXYETHYL PHOSPHORYLCHOLINE POLYMERS


TABLE II. Medical Devices used the MPC Polymers
Medical Device Product name
Guide wire Hunter
Stent BiodivYsio
TriMaxx
Drug eluting stent Dexamet
Endeavor
Artificial lung (oxygenator) Physio
Oxia ICN (Legacoat)
Microcatheter Londis
Catheter Eliminate
Artificial heart (LVAD) Evaheart
Contact lens Proclear
aquair evolution
Tympanostomy tube – Gyrus, Grace Medical
Artificial hip joint Aquala
MHLW; Ministry of Health, Labour and Welfare, Japan.
properties, the Dexamet was commercialized in 2001 as a
stent coated with crosslinked MPC polymer and preloaded
with the anti-inflammatory drug dexamethasone. Subse-
quently, MPC polymers were used by Abbott Vascular
Devices in the TriMaxx stent, and are also being developed
and clinically evaluated by Medtronic as coating for the
Endeavor stent.
Extracorporeal treatments of blood require systems
equipped with specific devices such as membrane oxygena-
tors and tubings. Accordingly, blood-facing surfaces have
been modified with PMD, an MPC polymer, to improve blood
compatibility. Italian company Sorin Biomedica has adopted
this approach for a range of extracorporeal devices to
enhance platelet preservation, as well as to suppress platelet
activity and complement activation.117 These devices also
suppress intraoperative thrombin formation and the associ-
ated consumption of platelets, fibrinogen, and antithrombin.
Moreover, EVEARHEART, an implantable LVAD, was
approved in 2011 in Japan after 6 years in clinical trial with
supporting by the JST.118 The device is a titanium alloy
coated with PMB30.100,119 Notably, PMB30 withstands blood
flow even after 7 months postimplantation, despite being
not chemical fixation on the surface. This resistance is attrib-
uted to its large molecular weight of the PMB30 (>5 × 105).
EVEARHEART has been implanted in more than 160 patients
in Japan, and is in clinical trials in the United States.
Ophthalmic devices
Ocular devices are another major commercial application of
MPC polymer.109 For example, soft contact lenses made from
poly(HEMA) hydrogels, which have been available since the
1980s, may sometimes prevent oxygen diffusion and provide
persistent mechanical irritation following adsorption of pro-
teins and lipids from tears. Thus, MPC polymer was investi-
gated as surface modifier to suppress protein adsorption
and enhance wettability. Subsequently, Biocompatible
Co. Ltd. has produced soft contact lenses (Proclear, Omafil-
con A) that contain 20% MPC unit, 80% HEMA unit, and
small amount of crosslinker, and which are now commer-
cially available from CooperVision Co.. Proclear is the only
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SPECIAL ISSUE
Manufacturer Clinical Introduction Year
Biocompatible 1997 (FDA approval: K970938)
Biocompatible 2000
Abbott Laboratories 2007
Biocompatible 2001
Medtronic 2008
Sorin Biomedica 2006 (FDA approval: K061031)
JMS 2015
Clinical Supply/Termo MHLW approval
Clinical Supply/Termo MHLW approval
Sun Medical 2011
Cooper Vision 1998
Cooper Vision 2009
2000 (FDA approval: K062672)
KYOCERA 2011
contact lens approved by the US Food and Drug Administra-
tion to reduce dry-eye syndrome. The proteins and lipids in
tears pass through the lenses without fouling them, provid-
ing nutrients and protection against bacterial infection. Being
strongly hydrophilic, MPC polymer also retains water, allow-
ing the tear film to wet the lens evenly and thereby prevent
formation of islands that may become fouled. Ultimately, this
reduces on-eye dehydration, and is particularly helpful for
dry-eye sufferers.
NOTES AND FUTURE PERSPECTIVE
MPC polymers have been clearly demonstrated over the
years as extremely wettable, and remain hydrated even
when exposed to the atmosphere. The substrates modified
with MPC polymer have high lubricity, and have low friction
coefficients similar to that of natural cartilage.71,72,120,121
Hence, developing new joints using poly(MPC) at interfaces
is an intriguing possibility.122
Extremely low-friction poly(MPC)-modified surfaces are
obtained using established methods of surface-initiated graft
polymerization. However, a new and simple technique of pho-
toinduced MPC polymerization was reported.68,71,72 In this
approach, the water-insoluble photoinitiator benzophenone is
deposited onto the substrate from acetone, and is then
exposed to ultraviolet light in an aqueous solution of MPC to
trigger polymerization. An artificial hip joint cup fabricated
from crosslinked ultra-high-molecular weight PE was modi-
fied in this manner.110 The resulting surface was found to
have high lubricity, also known as fluidic friction, and signifi-
cantly reduced wear. Based on these results and support by
the JST, conventional Aquala artificial hip joint systems from
KYOCERA Co. Ltd., Japan are now grafted with poly(MPC).
More than 52,000 of such systems have been implanted in
the patients from November 2011 to January 2019.
The history of MPC polymer-based biomaterials now
spans about 40 years, like that of the Japanese Society for Bio-
materials. In 1987, when Nakabayashi introduced to me an
initial history of the MPC polymer research, it was a great and
bright trigger for me to start the syntheses and characteriza-
tions including biological evaluations of the MPC polymers. In
939
particularly, in the last 30 years, the MPC polymers have been
demonstrated over all biocompatibility, that is, preventing sig-
nificant cell adhesion and tissue reactions by reducing protein
adsorption. Indeed, some MPC polymer-coated implantable
medical devices have been approved and are in use. In addi-
tion, MPC and MPC polymers have been commercialized
worldwide as reagents and as base of new polymer designs
with even better performance or novel features. Recently,
MPC polymer-like zwitterionic polymers, such as those based
on sulfobetaine and carboxybetaine, have been synthesized
and evaluated as the potential for biomaterials.67,123–127 It is
expected that continued research into polymer biomaterials
will advance minimally invasive medical care and regenera-
tive medicine in support of an aging society.
ACKNOWLEDGMENTS
Researches into MPC polymers as biomaterials, from the fun-
damental stage to the development of medical devices, have
been strongly supported by the Japanese Society for Bioma-
terials (JSB), and as well as by many members of the Society
for Biomaterials (SFB). Also, as industrialization and some
clinical trials have been supported by Japan Science and
Technology Agency (JST). The author expresses sincere
appreciation for these supports.
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