FULL PAPER
1800485 (1 of 12) ©
2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.mbs-journal.de
Validation of an MPC Polymer Coating to Attenuate
Surface-Induced Crosstalk between the Complement
and Coagulation Systems in Whole Blood in In Vitro
and In Vivo Models
Sana Asif, Kenta Asawa, Yuuki Inoue, Kazuhiko Ishihara, Björn Lindell,
Robin Holmgren, Bo Nilsson, Anneli Rydén, Marianne Jensen-Waern, Yuji Teramura,*
and Kristina N. Ekdahl
S. Asif, B. Lindell, R. Holmgren, Prof. B. Nilsson, Dr. Y. Teramura,
Prof. K. N. Ekdahl
Department of Immunology, Genetics and Pathology
Uppsala University
Dag Hammarskjölds väg 20, SE-751 85 Uppsala, Sweden
E-mail: teramura@bioeng.t.u-tokyo.ac.jp
K. Asawa, Dr. Y. Inoue, Prof. K. Ishihara, Dr. Y. Teramura
Department of Bioengineering
The University of Tokyo
7-3-1 Hongo, Bunkyo-ku, Tokyo 113–8656, Japan
DOI: 10.1002/mabi.201800485
Hemocompatibility
Artificial surfaces that come into contact with blood induce an immediate
activation of the cascade systems of the blood, leading to a thrombotic and/
or inflammatory response that can eventually cause damage to the bioma-
terial or the patient, or to both. Heparin coating has been used to improve
hemocompatibility, and another approach is 2-methacryloyloxyethyl phos-
phorylcholine (MPC)-based polymer coatings. Here, the aim is to evaluate
the hemocompatibility of MPC polymer coating by studying the interactions
with coagulation and complement systems using human blood in vitro model
and pig in vivo model. The stability of the coatings is investigated in vitro and
MPC polymer-coated catheters are tested in vivo by insertion into the external
jugular vein of pigs to monitor the catheters’ antithrombotic properties. There
is no significant activation of platelets or of the coagulation and complement
systems in the MPC polymer-coated one, which was superior in hemocom-
patibility to non-coated matrix surfaces. The protective effect of the MPC
polymer coat does not decline after incubation in human plasma for up to 2
weeks. With MPC polymer-coated catheters, it is possible to easily draw blood
from pig for 4 days in contrast to the case for non-coated catheters, in which
substantial clotting is seen.
B. Lindell
Department of Surgical Sciences, Plastic and Maxillofacial Surgery
Uppsala University
Dag Hammarskjölds väg 20, SE-751 85 Uppsala, Sweden
A. Rydén, Prof. M. Jensen-Waern
Department of Clinical Sciences, Faculty of Veterinary Medicine
and Animal Science
Swedish University of Agricultural Sciences
Almas Allé 8, 750 07 Uppsala, Sweden
Prof. K. N. Ekdahl
Linnaeus Center of Biomaterials Chemistry
Linnaeus University
SE-391 82 Kalmar, Sweden
The ORCID identification number(s) for the author(s) of this article
can be found under https://doi.org/10.1002/mabi.201800485.
1. Introduction
The quality of life of patients with a variety of medical condi-
tions has been improved as a result of the great progress made
in extracorporeal circulation devices and
artificial organs, including those used for
hemodialysis, hemofiltration, extracor-
poreal membrane oxygenation (ECMO),
cardiopulmonary bypass, ventricular
assistance devices, and plasmapheresis.
These medical devices are made of artifi-
cial materials such as synthetic polymers
and metals, which frequently come into
contact with blood and tissue fluids. The
most commonly used raw materials for
manufacturing these plastic devices are
segmented poly(ether urethane), poly-
tetrafuoroethylene, poly(vinyl chloride),
polyethylene, polydimethylsiloxane, cel-
lulose, polysulfone, and poly(ether ether
ketone).
[1]
In addition, various metals such
as titanium and its alloys have been used
in metallic devices.
[2]
Since these materials have limited
blood compatibility and biocompat-
ibility, systemic use of anticoagulants
is required to avoid clotting formation
when the medical devices are implanted
into patients or used ex vivo.
[3]
Once
the material is exposed to human whole blood, plasma pro-
tein adsorption immediately occurs, evoking a sequence of
events that includes activation, adhesion, and aggregation
of platelets; inflammatory reactions, including activation of
Macromol. Biosci. 2019, 1800485