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Current strategies towards hemocompatible coatings

Carsten Werner,*ab Manfred F. Maitza and Claudia Sperlinga
Received 6th March 2007, Accepted 6th June 2007
First published as an Advance Article on the web 27th June 2007
DOI: 10.1039/b703416b
Published on 27 June 2007. Downloaded by Mount Allison University on 01/06/2013 17:01:42.

A wide range of biomedical devices is applied clinically in contact with blood. Tailoring the
surface properties of the involved biomaterials is a common approach to enhance performance
and to limit adverse reactions. This review summarizes current trends in coating technologies
developed for that purpose. Inorganic coatings were shown to substantially improve the durability
and inertness of biomaterials while a number of advanced polymer coatings were demonstrated to
be very effective by targeting specific biochemical pathways. However, to fully utilize the power of
these bioactive coatings safety issues need to be thoroughly addressed in future studies.

Introduction The development of materials with improved hemocompat-

ibility therefore is an ongoing task. The blood reactions are
The wide range of biomedical devices directly contacting initiated by physical and chemical characteristics of the foreign
streaming blood include catheters, blood vessel grafts, vascular surface. Definition and control of these parameters are
stents, artificial heart valves, circulatory support devices, prerequisite for any blood compatible surface. To an increas-
various extracorporeal tubings, hemodialysis, hemapheresis ing extent, coating technologies combine the technological
and oxygenator membranes. Most of the biomaterials applied advantages of the bulk material with surface properties for
were selected primarily for technological aspects concerning appropriate performance in the biological ambiance.
mechanical properties, stability, permeability, processing,
price, and ease of sterilization, combined with non-toxicity
and a more or less acceptable hemocompatibility. Insufficient
hemocompatibility impairs functionality and safety through Claudia Sperling was born in
Dresden, Germany, in 1967.
the activation of blood coagulation and immune systems.
She studied biology at the
Clinical signs are the thrombotic occlusion of a vessel,
T e c h n i s c h e U n i v e r s i t ä t
embolia, proliferative processes in the vessel wall, and remote Mü nchen (diploma 1993)
effects like lung fibrosis or disturbed immune surveillance after and received her PhD from
hemodialysis treatment. Prophylactic systemic medication the Technical University in
frequently has to be applied to prevent these effects. Dresden (2001). Currently
her research topic is the hemo-
compatibility of biomaterials
a
Max Bergmann Center of Biomaterials Dresden, Leibniz Institute of including in vitro testing and
Polymer Research Dresden, Hohe Str. 6, 01069 Dresden. developing hemocompatible
E-mail: werner@ipfdd.de; Fax: +49-351-4653-533; coatings.
Tel: +49-351-4658-532
b
University of Toronto, Institute of Biomaterials and Biomedical
Engineering, Toronto, Canada Claudia Sperling

Carsten Werner was born in and molecular engineering of

Dresden, Germany, in 1965.
He studied chemistry at the
U n i v e r s i t y o f W ü r z b u r g
(diploma 1992) and received a
PhD at the Technical University
of Dresden in 1998. Since 2000
he has been head of the
Department of Biomaterials at
the Leibniz Institute of Polymer
Research Dresden, Germany,
and Adjunct Professor at the
University of Toronto, Canada.
His research interests comprise
Carsten Werner electrosurface phenomena at
solid–liquid interfaces, hemo-
compatibility of biomaterials
Manfred F. Maitz
extracellular matrices for stem
cell bioengineering.
Manfred F. Maitz was born in
Munich, Germany, in 1968. He
studied medicine in Würzburg
and there received a medical
degree in a biomaterials related
topic in 1997. Since then he has
been working in several institutes
for biomaterials or coating tech-
nologies. He has experience with
industrial application of inor-
ganic hemocompatible coatings
and polyurethanes in contact
with blood.

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Optimization of physical and chemical properties of the
surface presents the mechanism of passive hemocompatible
surfaces. Since healthy endothelium cells as the inner lining of
blood vessels are the physiological and most blood compatible
surface, it is intended to understand and simulate its properties
on active hemocompatible biomaterials.1,2
Physiological processes
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The adsorption of proteins and other molecules is the initial
event to occur when a foreign material is exposed to blood.
Hydrophobic surfaces adsorb larger amounts of proteins, an
effect which can be further influenced by surface roughness.
The temporal pattern of protein adsorption is governed by
displacement processes—commonly called the Vroman-effect.
Generally it can be found that small abundant blood plasma
proteins adsorb fast and sequentially are displaced by larger
proteins.3,4 The adsorbed protein layer differs not only in
composition from the proteins in plasma, but adsorbed
proteins also change their conformation with a possible
change of function or of immunological properties.5,6 This
early protein adsorption has an impact on further biological
processes, such as cell adhesion or activation of enzyme
cascades of coagulation or inflammation (Fig. 1).
According to the ISO standards, hemocompatibility covers
the categories thrombosis, coagulation, blood platelets,
hematology and immunology.7,8 The first three categories
may be summarized as haemostasis. In the following, these
areas will be described briefly.
Haemostasis can be divided into plasmatic (soluble) and
cellular aspects.
The plasmatic part of coagulation consists of a cascade-like
activation of inactive proteases, finally leading to the activa-
tion of thrombin, which is the key enzyme for the formation of
fibrin. Fibrin spontaneously assembles to fibrils, forming a
fibrin clot. Physiologically, there are two interconnected
pathways leading to the activation of the blood coagulation
cascade, where one typically depends on the exposure of blood
to extravascular tissue, whereas the other is activated by
adsorption and conformation changes of coagulation factor
FXII and high molecular weight kininogen at a surface. Blood
platelets (thrombocytes) present the cellular component of the
coagulation/thrombotic system. They are 3 mm sized spherical
to disc-shape anuclear cells, which can adhere to surfaces,
spread by forming pseudopodia, adhere to each other, release
growth factors and cytokines and enhance the humoral
coagulation system.
Immunoreactions (also cellular and plasmatic) to foreign
materials are mainly non-specific.
Fig. 1 Sequential process of surface/biofluid interaction symbolizing
the impact of surface characteristics, ion and protein adsorption on cell
adhesion processes.
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Fig. 2 Complement activation on model surfaces—influence of the
amount of OH surface groups. Self assembled monolayers containing
either C11-OH or C10-COOH in different amounts (C11-OH: 0; 49; 89
or 100%) were incubated for 2 h with fresh whole human blood
(heparinized with 2 IU ml21) under controlled conditions The
complement activation was found to be closely related to amount of
OH surface groups.
The leading effector of the soluble non-specific immune
system is the complement system. Similar to the coagulation
cascade it consists of a number of proteases, which activate
each other in a cascade-like process. Consequences are the
opsonisation of the target for facilitated phagocytosis, activa-
tion of non-specific inflammatory cells (granulocytes and
monocytes), and attraction of these cells (chemotaxis). The
complement system also has various pathways of activation,
where the alternative pathway is most relevant for biomater-
ials. It is initiated by hydrolysis of the complement factor C3
and covalent binding of the major C3b fragment to nucleo-
philic hydroxyl or amino groups of the surface. This reaction is
directly correlated to the amount of hydroxyl groups on model
surfaces (Fig. 2).9 Minor complement fragments act as
activators of granulocytes and monocytes.10,11
Hematology as the last category contains changes in the
number of blood cells during contact with blood. The decay of
the number of white blood cells and blood platelets is usually
covered by the immunological and haemostatic categories.
Hemolysis, which causes a decay of red blood cells remains the
leading parameter in this field.
Basic physical and chemical surface properties
Before the discussion of current methods of surface modifica-
tion for improved hemocompatibility, the general influence of
surface energy, charge and topography have to be taken into
account. Despite their clear definition and long-term evalua-
tion, their influence in the complex system of blood remains
ambiguous.
Highly hydrophobic surfaces and surface modifications
adsorb more proteins from plasma and induce more con-
formation changes of the adsorbed proteins.12,13 Conforma-
tion changes and expression of neoepitopes promotes
inflammatory reactions, cell adhesion and blood platelet
adhesion.5 Uncharged hydrophilic surfaces therefore fre-
quently have low interaction with proteins and blood in total,
J. Mater. Chem., 2007, 17, 3376–3384 | 3377

however this trend cannot be generalized, as plasma oxidation
of polyethylene caused increased wettability with increased
protein adsorption but reduced blood platelet adhesion.14
Otherwise highly hydrophobic surfaces of expanded polytetra-
fluorethylene (ePTFE) or other fluorinated surfaces also
express high hemocompatibility.15,16
Negative surface charges activate the plasmatic coagulation
system,17–19 whereas positive charges stimulate blood platelet
adhesion and activation19,20 and enhance the activity of the
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coagulation factor FVIIIa in plasma.21 Specific effects, like of
the highly negatively charged heparin can reverse these
effects.22
Hydroxyl and amino groups are activators of the alternative
pathway of the complement system.11 This also is correlated to
leukocyte adhesion—a process which can be attributed to a
ligand binding of adsorbed C3b to complement receptors.23
Smooth surfaces generally adsorb less proteins than rough
surfaces,24,25 air bubbles, captured in a rough surface, are
complement activators.26 Roughness and turbulent blood flow
are strong activators of blood platelets. A surface texture
under flow conditions, however, can reduce shear forces and
support endothelialization.27–29
Inorganic coatings
Inorganic hemocompatible coatings already have clinical
application as coatings of metallic devices, such as vascular
stents or mechanical heart valves. These coatings mainly
belong to the classes of metal oxides, nitrides and carbon
based inorganic coatings like hydrogenated amorphous carbon
(a-C:H, frequently referred to as diamond-like carbon DLC).
Other ceramics are under consideration, but have still been
investigated and applied rarely.30 Generally, the inorganic
coatings exhibit high inertness, mechanical and chemical
stability. This predestines them as mainly passive hemocom-
patible coatings and corrosion protection.
The carbon based coatings currently have the widest
application of the inorganic coatings on artificial heart
valves31,32 and on vascular stents.33 They are excellently inert
in biological ambiance. High smoothness, low friction and
minimal wear renders them first choice for the mobile parts of
the heart valve. The high hydrophobicity of the coating
induces high plasma protein adsorption with a predominance
of protective albumin over fibrinogen, but also an enhanced
adherence of blood platelets.31,34 The application of DLC has
limitations due to carbide formation in contact with iron. As
an alternative, boron-carbon-nitrogen coatings with similar
mechanical and biological properties have been suggested.35
Among the ceramics, titanium oxides and titanium nitrides
are most widely investigated for blood compatibility. While the
naturally grown oxide film on titanium exhibits low blood
compatibility,36,37 thicker oxide films generally prove very
hemocompatible.38,39 Various techniques for increasing the
natural oxide film on titanium or titanium alloys (including
nitinol) have been examined,38–41 further, energetic and sol–gel
film deposition techniques have been applied for coating of
irrelevant substrates.42–46 Titanium nitrides and oxynitrides
are produced by energetic nitriding and film deposition
techniques.47–49 Titanium oxide films adsorb less fibrinogen
3378 | J. Mater. Chem., 2007, 17, 3376–3384
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on the surface and induce less activation of the coagulation
cascade,50 show strongly reduced blood platelet adhesion39,46
and exhibit lower coagulation activation39 than the untreated
surface or DLC. Superior performance of titanium
oxide42,46,51,52 and oxynitride53 also have been demonstrated
in vivo in blood flow.
The semiconductor titanium oxide as a coating can be
present in several crystal structures and orientations, which
exhibit very different surface energies.54,55 This is superposed
by its photochemical effect.54,56 This is seen as the reason for
the general good hydrophilicity and low protein adsorption of
this coating. The semiconductive properties are also the base
for the free radical scavenging and anti-inflammatory proper-
ties of titanium oxide.57 Additional inhibitory effects of
the semiconductor titanium oxide on the conversion of
surface adsorbed fibrinogen to fibrin have been discussed by
several groups.58–60 n-Type doping of titanium oxide with
phosphorpous61 or tantalum58 has been performed to
further optimize the electronic band properties for improved
hemocompatibility.
Amorphous silicon carbide (a-SiC:H) has similar semicon-
ductor properties to titanium oxide and is commercially
applied as a coating on vascular stents and heart valves.62–64
An additional benefit in clinical studies was seen for iridium
oxide film on vascular stents, which was attributed to the
peroxide scavenging effect of the coating.65,66
Organic surfaces
A variety of polymeric materials are used as biomaterials in
biomedical applications with blood contact. For hemodialysis
membranes polyethersulfone and regenerated cellulose are the
most important materials. Oxygenator membranes are largely
made from polysiloxane or polypropylene and the main
material for vascular grafts is warp knitted or woven polyester
textile (Dacron1) and expanded polytetrafluorethylene foils
(GoreTex1). A wide range of materials is used for catheters;
depending on the type of application and duration of
application polytetrafluorethylene, polyethylene, polyvi-
nylchloride, polyurethanes and polysiloxane are used, poly-
ether block amides (PEBAX1) are applied for balloon
catheters.67–71 The polymers generally allow wider accessibility
for chemical surface modification than inorganic substrates,
however, they are also more prone to modification and
hydrolytic degradation in biological ambiance.
Three approaches for hemocompatible surface modification
can be worked out, which will be described in the following in
more detail. (1) Passivation of the surface to attain minimal
interaction with blood proteins and cells. (2) Immobilization of
active molecules to interact with blood proteins and cells. (3)
Promotion of the growth of endothelial cells.
Surface passivation
Surface passivation is performed to minimize the interaction of
proteins and cells with the surface.
Brushes of long-chained hydrophilic molecules like poly-
ethylene oxide (PEO)72,73 or the related molecules polyethylene
glycol (PEG)74–76 or tetraethylene glycol dimethyl ether
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(tetraglyme)77 and others are known to be biologically inert
and display excellent biocompatibility.78 They have been
suggested for hemocompatible surface modification. Methods
of surface modification with these molecules range from
physisorption, various methods of covalent bonding of
the functionalized molecule, to integration as block segments
in polymers as reviewed elsewhere.79 Applications are
microencapsulation of cells;80–82 coatings on dialysis mem-
branes,83–85 stents86 and stent grafts;87 further drug release
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systems.88
The hydrophilicity of PEO surface modification is depen-
dent on the molecular weight of the PEO, thus also the protein
adsorption decreases with increasing chain length of the PEO
and remains relatively constant for Mr . 2500 g mol21.79
Reduced coagulation activation, blood platelet adhesion and
complement activation has been found for such modified
surfaces.85
Due to these excellent properties in surface passivation,
PEG and related molecules are frequently used as spacer
molecules for immobilization of bioactive molecules on a
surface. They provide sufficient distance to shield influences of
the substrate on the immobilized molecule or its biological
binding partner. Further, they provide sufficient flexibility to
facilitate the steric interaction of the immobilized molecule
with its receptor biological binding partner.
Surface decoration with inert biomolecules is another
frequent approach to obtaining surface passivation. Albumin
is predominantly selected for this application, because with a
concentration of 35–53 g L21 it is the main molecule in blood
plasma. The physiological functions of the non-glycosylated
66.3 kDa globular proteins are maintaining the colloidosmotic
pressure and transport of low molecular weight molecules, but
it has no involvement in haemostasis or immunologic
processes. Coating a surface with this molecule therefore is
regarded as masking the device from the immune system and
coagulant processes.89–92 The method however has limitations
due to conformational changes of the adsorbed molecule,
exchange processes, physiological degradation of the protein.
Sterilization and a limited shelf stability cause technological
problems. Due to the human origin of the protein, a risk of the
transmission of infectious diseases also remains.
In a similar approach to surface masking with albumin,
phosphorylcholine is used to mimic the membrane of native
cells.93,94 This type of coating was evaluated for dialysis
membranes.95–97 and already has successful clinical application
on vascular stents.98
Bioactive coatings
Immobilization of molecules is not restricted to passivation of
a surface. Endothelial cells as the inner lining of the blood
vessel wall possess several active anticoagulant mechanisms,
which gain interest and are reproduced by immobilization on a
surface. The range of molecules is further expanded from
physiological molecules to biological molecules from different
species and to synthetic drugs. For targeting complex
receptor–ligand interactions, an oriented immobilization and
suitable presentation of the molecules is relevant and currently
presents one of the leading challenges in this area. A second
This journal is ß The Royal Society of Chemistry 2007
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problem is the high susceptibility of biomolecules to physio-
logical degradation processes, which quickly deactivates the
modification. Technological issues occur from sterilization and
limited shelf stability.
The sulfated mucopolysaccharide heparin as the analogue to
the cell surface anticoagulant heparan sulfate and leading
clinical anticoagulant also has been the first anticoagulant to
be immobilized for improved hemocompatibility.99 It rapidly
found application as surface modification on tubings and
oxygenator membranes in extracorporeal circulation,100–102
dialysis membranes,103 vascular stents,104,105 stent grafts,106
bypass grafts107,108 and ventricular assist devices.109 Coating
technologies have been summarized elsewhere.110 They range
from physisorption99 over covalent end-point immobiliza-
tion,111,112 to albumin–heparin multilayers.113
The anticoagulant activity of heparin requires the protein
antithrombin III (AT III), which binds to heparin and in this
complex has severely enhanced affinity to the target molecules
thrombin and coagulation factor FXa of the coagulation
cascade.110 Heparin in addition has anti-inflammatory proper-
ties by inhibiting the complement system.17,114 An AT III
binding capacity of 6–12 pmol cm22 of a heparinized surface
was found to present the optimal heparin surface concentra-
tion.115 For long-term applications heparin-coatings suffer
from a short half-time of the molecule. Further, surface-bound
heparin has only 1% of the activity of free heparin113 and it is
ineffective against fibrin-associated thrombin.116–118 Clinical
systemic heparin inactivation with protamine sulfate, as is
typical after extracorporeal circulation, also inactivates
heparin on a device.
The complex interactions of heparin with AT III could be
reduced to few basic structure–function relations. A sulfated
pentasaccharide structure instead of the long-chain heparin is
sufficient for the AT III mediated inhibition of FXa.119,120
These structures are more resistant against enzymatic degrada-
tion than the whole heparin molecule. More recent studies
showed that the sulfate groups are sufficient for binding AT
III, an effect, which is further enhanced by a saccharide and
polysaccharide backbone. This heparin-affinity to the inhibitor
mainly did not lead to a heparin-like activity of the
immobilized molecule in complex blood,121 in similar experi-
ments with beads, which exhibit a better surface volume ratio,
an anticoagulant effect was observed.122,123 Sulfonation of
polyurethanes116,124 or chitosan20 has been performed with the
same intention.
The anticoagulant effect of these surface modifications is
still dependent on the protein AT III, which may be deficient in
septic situations. Direct thrombin inhibitors therefore gained
more interest. Hirudin and recombinant analogues have been
the first molecules tested there, mainly for the long-term
clinical experience with systemic administration.125,126
However, as a hemocompatible coating these molecules have
not exceeded the laboratory state yet. Hirudin has different
binding places to thrombin and AT III, therefore it is effective
also against fibrin-bound thrombin. The hirudin-like thrombin
inhibitors can form irreversible complexes with thrombin
(hirudin, lepirudin and desirudin)127 or they are a substrate
(bivalirudin).128 Recombinant hirudin has been covalently
immobilized to polyester (Dacron1) for vascular grafts or
J. Mater. Chem., 2007, 17, 3376–3384 | 3379

Fig. 3 Scanning electron microscope pictures of adherent cells and
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fibrin formation on surfaces after incubation with fresh whole human
blood (heparinized with 2 IU ml21). Surfaces left: negatively charged
surface poly(octadecene alt maleic anhydride) (PO-MA); right:
immobilization of a molecular level optimized, benzamidine derived
direct thrombin inhibitor on PO-MA using HOOC–PEG12–COOH as
a spacer. The immobilization decreases fibrin formation and cell
adhesion onto the surfaces compared to the reference without spacer
and thrombin inhibitor (for further effects see published article133).
patches129–131 or to a polylactide–polyglycolide membrane.132
The anticoagulant properties of these materials have been
demonstrated in vitro or evaluated as arterial patches in short-
term animal studies in vivo.
There are several synthetic low molecular weight inhibitors
of thrombin, which have not gained medical application due to
their low specifity. Benzamidine derived reversible inhibitors
have been molecular designed for enhanced affinity and
specifity for thrombin and immobilized as hemocompatible
coating on model substrates (see Fig. 3).133 In addition to
anticoagulant properties anti-inflammatory effects were also
found.134
Another physiological and very potent thrombin inhibitor
besides AT III is the 105 kDa protein thrombomodulin (for
experimental results see Fig. 4). It is an integral part of the
endothelial cell membrane and binds thrombin with high
affinity. Other than the synthetic inhibitors or hirudin it
additionally enhances the substrate specifity of thrombin for
Fig. 4 Coagulation activation (measured as Thrombin–Antithrombin
Complex TAT) and platelet activation (measured as Platelet Factor 4
PF4) after incubation with fresh whole human blood (heparinized with
2 IU ml21). Materials were references glass and polytetrafluorethylene
(PTFE) and immobilized thrombomodulin (TM) (immobilization onto
maleic acid anhydrid copolymer).174 The reference glass presents a
high activation surface. PTFE is an established biomaterial.
Thrombomodulin modification significantly enhances the hemocom-
patibility for both parameters. (TAT p , 0.001 for TM versus glass,
PTFE; PF4 p , 0.001 PTFE versus TM, p = 0.002 glass versus TM;
significance was tested in One-Way-Anova with subsequent pair-test
according to Student-Newman-Keuls.)
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activation of the anticoagulant protein C. Besides the antic-
oagulant properties, thrombomodulin possesses several anti-
inflammatory principles influencing cell adhesion and comple-
ment activation.135–137 The molecule has been immobilized
covalently on model substrates without138,139 and with spacer
molecules.140 A reduction in coagulation activation, platelet
adherence and inflammatory reactions was seen in all cases,
however, the modification has not come to clinical application
yet due to high expense and a possible degradation of the
molecule in vivo.
The above-mentioned strategies emphasize the inhibition of
the humoral coagulation activation with only a passive impact
on platelets. The active inhibition of platelet activation and
aggregation through (drug-eluting) coatings also is possible.
Dipyridamol—an ADP (adenosine diphosphate) receptor
antagonist141 and GPIIb/IIIa inhibitor (abciximab,142
Tirofiban143)—was reported in this context. The release of
nitric oxide from a coating also affects thrombocyte adhesion
and aggregation144,145 yet cytotoxic effects were also found.146
The modification of stents with biodegradable or non-
degradable coatings147,148 is only partly dedicated to coagula-
tion and platelet inhibition. Recent developments strengthen
the inhibition of smooth muscle cell proliferation. This
complex issue is summarized in ref. 149.
Promotion of endothelialization
As the endothelium is the physiological and most hemocom-
patible blood contacting surface, the stimulated growth of
these cells on the foreign materials is tightly focused. This type
of surface modification has the advantage of producing a
permanently active hemocompatible surface. Only a few basic
principles of this tissue engineering approach will be addressed
here. Detailed information can be found in an up-to-date
review by McGuigan and Sefton.150
Applied methods range from two-step approaches with
harvesting autologous endothelial cells, ex vivo cultivation and
implantation of the device in a second procedure.151,152 The
adhesion and growth of the cells is supported by immobiliza-
tion of the whole extracellular matrix,153 selected proteins in
the extracellular matrix154–157 or peptide sequences, which act
as ligands for cell adhesion proteins.156,158 As these extra-
cellular matrix compounds are highly thrombogenic, complete
coverage with endothelium is required before blood contact.
Immobilization of endothelium specific antibodies, however
can capture endothelium precursor cells from circulation and
allow their final differentiation on the device, as demonstrated
in a successful clinical pilot study.159 Drug release of growth
factors, mainly vascular endothelial growth factor VEGF, to
stimulate endothelialization from local cells has been tested
successfully in animal studies,160 but it was not followed
further because of the rapid degradation of the factor. Current
approaches, which are in clinical studies, apply transfer of the
growth factor gene and local expression of the protein.161–164
Hemocompatibility assessment
An essential part of the development of hemocompatible
coatings concerns the analytical evaluation of their safety and
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performance. Despite the recommendations of the European
Committee for Standardization (CEN) and the U.S. Food and
Drug Administration (FDA), the choice of in vitro and in vivo
methods to be applied for that purpose is critical with respect
to the quality of the obtained information. The vast majority
of simple approaches have severe limitations. We developed
customized incubation systems using non-flowing or flowing
human blood, blood plasma or cells (PRP, PFP).165
Depending on the intended use, other incubation systems
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implementing tubes (e.g. Chandler loop model), hemodialyzer,
etc. are applied. The diagnostics of surface and blood after
incubation encompass a range of microscopic techniques
enabling quantitative and qualitative conclusions (see Fig. 2
and 3). Clot formation was the first parameter for coagulation/
thrombocyte activation but soon was refined to the monitoring
of activation parameters166 using e.g. immunologic techniques
and activity assays and is complemented now by a wide range
of cell and molecular biology techniques.167
Conclusions and outlook
Undesired biological reactions of blood at the surfaces of
biomedical devices are targeted by a range of surface
modification schemes. However, the superposition of mechan-
istically distinguished processes and the resulting contradicting
requirements for their control limit the options for optimiza-
tion. In general, organic coatings influence the hemocompat-
ibility of materials on a molecular level, yet the stability of
inorganic coatings is usually better. This currently determines
the choice of the type of coating for any particular device.
Additionally, economic restrictions like the current reim-
bursement policies for advanced devices make fast replacement
of common practice improbable.168–170
Resuming, strategies for hemocompatible biomaterials cover a
wide range from passivation of surfaces, to functionalization
using interacting molecules, to the use of endothelial cells for
surface lining. Some strategies seem to be more promising like
the already commercially used heparinization and also the
surface modification with thrombomodulin showing a strong
inhibitory potential of immune and coagulation reactions. Yet
especially long-term stability and sterilization also effects the
practical implementation. The above-mentioned approaches all
have in common that they aim at a permanent control of surface
characteristics of artificial materials in the sense of a ‘‘magic
cap’’. A promising alternative to this principle seems to come
within reach with the advent of tissue engineering: temporary,
degradable (bio)polymeric templates directing the cellular
potential for regeneration of tissues are explored as possibly
safer substitutes for vascular grafts and heart valves. A number
of recent publications describe the possibilities of engineering
grafts using autologous cells and tissues.171–173 However,
molecular functionalization of polymer scaffolds developed for
that purpose is essential for the success of any regenerative
therapy and bioactive coatings play a key role here again.
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