Biomaterials 20 (1999) 1365}1370

Anti-in#ammatory properties of triblock siloxane

copolymer-blended materials
Liping Tang *, Min-Shyan Sheu
, Taiming Chu, Yeong Hua Huang
Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA

Advanced Surface Technology Inc., Nine Linnell Circle, Billerica, MA 01821-3902, USA
Department of Mechanical Engineering, New Jersey Institute of Technology, University Heights, Newark, NJ 07102, USA
Datascope Corporate, 15 Law Drive, Fairxeld, NJ 07004, USA

Abstract

Implantable biomaterials often trigger a variety of adverse responses. Because polydimethyl siloxane surfaces have good hemo- and
bio-compatibility, it is generally believed that surface biocompatibility may be improved by modifying biomaterial surfaces with
silicone-like properties. For this, we developed a series of polycaprolactone}polydimethylsiloxane}polycaprolactone (PDMS}PCL)
copolymers. By mixing the substrate material*polyvinyl chloride*with low concentrations (1.2 and 2.4%) of the PDMS}PCL
copolymer, we generated materials with silicone-like surface properties as re#ected by increased surface silicon content and surface
contact angles. We assessed the biocompatibility of these surfaces in vitro and found that the addition of PDMS}PCL signi"cantly
reduced the percentages of surface-&denatured' "brinogen, a critical element of genesis of many adverse responses to implanted
biomaterials. Indeed, using an animal implantation model, we "nd that PDMS}PCL-blended materials triggered signi"cantly weaker
in#ammatory responses than did polyvinyl chloride, the substrate control. The results from these experiments suggest that the use of
PDMS}PCL additives (2.4%) in polymer blends is a useful means of camou#aging the substrate surface properties and improving the
biocompatibility of biomaterials.  1999 Elsevier Science Ltd. All rights reserved

Keywords: Polycaprolactone}polydimethyl siloxane}polycaprolactone; Polyvinyl chloride; Fibrinogen; In#ammatory responses

1. Introduction stability) and hemo-/bio-compatibility [21}23]. How-

Both blood-contact and tissue-contact biomaterials
trigger adverse responses such as thrombosis [1, 2],
complement activation [3}8], in#ammation (typically
accompanied by the accumulation of phagocytic cells)
[9}11], and device-centered infections [12}14]. Thus,
intensive research e!orts have focused on modifying surface
physical and chemical properties to generate surfaces
with better biocompatibility and/or blood compatibility
[15}20]. Among many commonly used biomaterials,
polydimethylsiloxane (PDMS) has been used extensively
and shown to have good physical properties (including
low-surface tension/energy, extreme hydrophobicity,
high-chain #exibility, good oxidative, thermal and UV
* Corresponding author. Tel.: 001-713-798-5467; fax: 001-713-790-
0617; e-mail. ltang@neo.bcm.tmc.edu
ever, due to poor mechanical properties and cold #ow
even at very high-molecular weights (MW 500 000 D),
pure PDMS cannot be used directly to make medical
devices. To solve the problem, PDMS is commonly "lled
with high percentages of silica (up to 40}50% by weight)
and cross-linked using various methods, which compro-
mise many material properties and limit the use of this
material [24}26].
In order to generate silicone-like surfaces without af-
fecting mechanical properties of substrate materials, vari-
ous forms of PDMS have been used as additives in
several conventional polymers [27, 28]. Because these
PDMS are extremely non-polar and have very low-ex-
perimental solubility parameters, they are thermody-
namically incompatible with almost all other organic
polymers [29]. As a result of their incompatibility and
chain mobility, when PDMS or siloxane containing
copolymers are blended with various organic polymers,
the air-polymer surfaces of the resulting systems are

0142-9612/99/$ - see front matter  1999 Elsevier Science Ltd. All rights reserved.
PII: S 0 1 4 2 - 9 6 1 2 ( 9 9 ) 0 0 0 3 4 - 4
1366 L. Tang et al. / Biomaterials 20 (1999) 1365}1370
dominated by the low-surface energy siloxane. Thus,
even at very low levels of bulk siloxane content (0.5}5.0%
by weight), the resultant blends display completely sili-
cone-like surface properties [27, 28]. However, due to the
lack of covalent linkage, pure PDMS does not stay on
surfaces over a long period of time. An e!ective way
of achieving stable surface modi"cation in such blends
is through the use of siloxane-containing block copoly-
mers. In these systems the organic component of the
siloxane copolymer provides miscibility with the base
polymer while siloxane segments migrate to the air-poly-
mer interface. Therefore, in essence, these organic seg-
ments act as &anchoring groups' for the siloxane blocks
and thereby provide &permanent' surface modi"cation.
Because of a wide choice of organic blocks, various types
of siloxane copolymers have been designed and syn-
thesized to achieve optimum compatibility with the base
resin utilized [24, 27, 28, 30].
One of the earliest studies of surface-modifying addi-
tive-containing copolymers was reported by Zisman et al.
[31] in 1967. Since then many PDMS-based surface
modifying additive-containing copolymers have been
synthesized and shown to e!ectively modify material
surfaces with silicone-like surface properties [24, 27, 28,
30, 32]. However, to the best of our knowledge, the
biocompatibility of these silicone-like surfaces has not
been evaluated. By measuring surface-mediated protein
adsorption in vitro and in#ammatory responses in vivo,
we attempted to assess the biocompatibility of polyvinyl
chloride (PVC) blended with di!erent concentrations (1.2
and 2.4%) of siloxane-containing block copolymers.
PVC was selected as the substrate because it is widely
used in the medical device industry, often in application
requiring direct blood and tissue contact. A commercial-
ly available triblock copolymer of polycaprolactone}
polydimethylsiloxane}polycaprolactone was chosen to
produce silicone-like surfaces.
2. Materials and methods
2.1. Materials
I-human "brinogen was obtained from ICN Bio-
medical Inc. (Costa Mesa, CA). Sodium dodecyl sulfate
(SDS), horseradish peroxidase, guaiacol (O-methoxy-
phenol), hydrogen peroxide (30% solution), eserine
(physostigmine), O-nitrophenyl butyrate, dimethyl silo-
xane, tetrahydrofurane (THF) and Triton X-100 (octyl
phenoxy polyethoxyethanol) were purchased from Sigma
Chemical Co. (St. Louis, MO).
Surface-modifying additive PDMS was obtained from
Goldschmidt Chemical Co. (Hopewell, VA) and used as
received. It is a hydroxy-terminated polycaprolactone}
polydimethylsiloxane}polycaprolactone (Tegomer
hereafter abbreviated as PDMS}PCL) copolymer with
a molecular weight of 6500 D. The PDMS}PCL copoly-
mer was compounded at 1.2 and 2.4% (w/w) with a medi-
cal grade polyvinyl chloride to generate test tubing and
"lms using a twin screw extruder and THF solution
casting, respectively. All experimental results are com-
pared with control PVC and polydimethyl siloxane "lm
(Dow Corning Corp., Midland, Michigan).
2.2. Sample preparation
Except for rheological studies, disks of 1.2-cm diameter
were cut from test surfaces. These disks were sonicated
three times (5 min each time) in 70% ethanol, with
frequent changes of ethanol, to remove dust and to
sterilize the surfaces. Before use, the disks were hy-
drated by immersion in sterile, pyrogen-free saline for at
least 1 h.
2.3. Rheological measurement
It is well known that additives in the polymer com-
pound may change not only the physical and chemical
properties of the material, but also the parameters
needed to process the materials. The most common indi-
cator used to assess these changes is the rheological
properties of the material. A Kayness Dynasty IV Capil-
lary Rheometer was used to evaluate changes in shear
viscosity under various shear rates as described earlier
[33}36]. The results were then compared with control
PVC tubing.
2.4. Contact angle measurement
The wettability of the samples was evaluated using
water contact angle measurements. A computer-video
processed goniometer, VCA-2500 (Advanced Surface
Tech., Billerica, MA), was used to take these measure-
ments. A sessile drop of DI water was dispensed onto the
"lm and its image was captured by a video camera and
displayed on a computer monitor. The contact angle of
the water drop was then determined using computer
software.
2.5. X-ray photoelectron spectroscopy (XPS or ESCA)
XPS measurements were carried out in an SSX-100
spectrometer (Surface Science Instruments, Mountain
View, CA) using a monochromatic AlKa X-ray source,
a detection system with a 303 solid angle acceptance and
a hemispherical analyzer as published earlier [37].
A 5 eV #oodgun was applied to compensate for the
surface charging of polymer samples. The X-ray spot size
(area analyzed) on the sample surfaces was approxi-
mately 1 mm in diameter. A standard 553 take-o! angle
(the angle between the surface normal and the axis of
the analyzer lens) was used for surface scans. Surface
 L. Tang et al. / Biomaterials 20 (1999) 1365}1370
compositions determined from XPS spectra were used to
examine the existence of the siloxane component.
2.6. Measurement of adsorbed and *denatured+
xbrinogen
The amounts of spontaneously adsorbed and &de-
natured' "brinogen on di!erent surfaces were determined
radiometrically. For this, the samples were incubated
with I-human "brinogen ("nal concentration
20 lg/ml) for 4 h at 373C, on a rotary shaker set at 50
rounds per minute (RPM). The samples then were thor-
oughly rinsed with phosphate-bu!ered saline (PBS,
50 mM, pH 7.4) and half were incubated with 1% SDS for
1 h (also shaken at 50 RPM) in order to remove elutable
(non-denatured) "brinogen [38]. Ratios between the sur-
face-associated radioactivity on disks rinsed with 1%
SDS vs. PBS were taken as a measure of the percentages
of surface-denatured "brinogen [39, 40].
2.7. Experimentation and measurements of host responses
As an in vivo model for assessing biomaterial-me-
diated in#ammatory responses, di!erent samples were
implanted intraperitoneally in Swiss Webster mice (male,
20 g body weight) (Taconic Farms, Inc., Germantown,
NY) as described earlier [41}43]. Explantation was per-
formed at 16 h after implantation (earlier found to be the
approximate time of maximal phagocyte accumulation).
After careful removal from the peritoneal cavity, ex-
planted disks were gently washed with PBS. The adher-
ent cells were then lysed by incubating the disks with 0.6 m
of 1% (v/v) Triton X-100 for 1 h (to release cytosolic and
granular contents of adherent cells). The numbers of
adherent phagocytes were then estimated by determining
enzyme activities (myeloperoxidase [MPO] for
neutrophils and nonspeci"c esterase [NSE] for macro-
phages/monocytes [M ]) to re#ect the extent of
biomaterial-mediated in#ammatory responses [41, 42].
Previous control experiments showed that surface-asso-
ciated enzyme activities are reliable indicators of the
numbers of adherent phagocytes [41, 42]. We have
previously determined that the MPO activity of mouse
peripheral neutrophils and the NSE activity of mouse
peritoneal resident macrophages are &23 and &11 nU/
cells, respectively [41]. Experimental values shown in all
graphs represent the results of single implantation experi-
ments using "ve animals per group. All such experiments
were repeated at least three times to ensure the reproduc-
ibility of our results.
2.8. Statistical analysis
Signi"cance of di!erences among variously coated sur-
faces was assessed using two-tailed Student's t test.
1367
3. Results and discussion
3.1. Surface characterization of PDMS}PCL blended
materials
Earlier and our preliminary studies have established
that, by blending a small percentage (1}3%) of PDMS-
copolymer with polyvinyl chloride, the resulting materials
display silicone-like surface properties [24]. However,
the compatibility of the PDMS-copolymer-modi"ed sur-
faces has not been evaluated. In the present studies,
PDMS}PCL block copolymer was employed as the sur-
face modifying additive for biomaterials. After blended
polyvinyl chloride with di!erent weight percentages (1.2
and 2.4%) of PDMS}PCL, the change of surface func-
tionality and properties was determined by ESCA, con-
tact angle and shear viscosity measurements. As shown in
Table 1, by comparing these data with those obtained
from pure PVC and PDMS, we observed that the addi-
tion of PDMS}PCL copolymer at both 1.2 and 2.4%
generates silicone-like surfaces on PVC. Speci"cally, the
addition of PDMS}PCL signi"cantly increased the sili-
con and oxygen contents on biomaterial surfaces. Obvi-
ously, PDMS, but not PVC, surfaces have silicon. On the
other hand, the disappearance of substrate atomic com-
ponents, such as chloride, indicated that the modi"ed
surfaces are sheltered under PDMS. In addition, the
supplement of PDMS}PCL compound resulted in an
increase of hydrophobicities from 87 to 1003 and 1063 for
1.2 and 2.4% PDMS}PCL, respectively. The increase of
contact angle after adding PDMS}PCL compound fur-
ther supported the idea that PDMS segments, which are
highly hydrophobic, have migrated onto the surfaces.
For manufacturing purposes, we also have tested
whether the addition of PDMS}PCL copolymer changes
the melting viscosity of substrate polymer. Knowledge of
the #ow properties of the polymer melts is very impor-
tant in determining whether it is capable of withstanding
the manufacturing process, such as extrusion and injec-
tion molding. Knowledge of the melt #ow properties
allows accurate optimization of the process operating
Table 1
ESCA surface analyses and contact angle measurements of PVC,
PDMS}PCL-added PVC, and PDMS
Test surface Atomic percentages Contact
angle
Si Cl C O
PVC 0 22.52 70.21 7.27 87$4
PVC#1.2% 9.71 5.03 63.60 21.63 100$3
PDMS}PCL
PVC#2.4% 9.26 0.34 66.90 23.50 106$10
PDMS}PCL
PDMS 27.07 0.00 45.06 27.87 118$2
1368 L. Tang et al. / Biomaterials 20 (1999) 1365}1370

conditions. Indeed, our results have shown that the sup-

plement of PDMS}PCL decreased the shear viscosity of
polymer surfaces (Table 2). This reduction of shear vis-
cosity was probably caused by the smaller molecular
weight of PDMS}PCL (average MW 6.5 KD) vs. that of
PVC (average MW 200}260 KD). Therefore, it is likely
that the addition of siloxane copolymer may not only
sustain the process control but also add the throughput
with the reduction of viscosity, which in turn increases
the melt index.
Because PDMS}PCL blended PVC expressed PDMS
surface properties and PDMS possesses an unique
physiological inertness, we hypothesized that the supple-
ment of siloxane additive improves the biocompatibility
of substrate materials, such as PVC.

3.2. Fibrinogen adsorption and *denaturation+ on

test surfaces

Because protein adsorption is much more rapid than

transport of cells to implanted biomaterial, host cells
probably interact with adsorbed proteins rather than
with the foreign material itself. Thus, the type and state of
adsorbed proteins are critical determinants of biocom-
patibility [44}46]. Many others and our studies have
found that the amounts and states of adsorbed "brinogen
are a critical determinant of blood and tissue compatibil-
ity of biomaterial implants [41, 43, 47}49]. Thus, the
amounts of adsorbed and &denatured' "brinogen on dif-
ferent surfaces were measured as an indicator of biocom-
patibility.
By comparing with PVC substrate materials, we deter-
mined that the addition of PDMS}PCL signi"cantly
increases the amounts of adsorbed "brinogen (Fig. 1a).
However, the percentages of SDS-inelutable (denatured) Fig. 1. I-human albumin (20 lg/ml) adsorption to (A) and non-
"brinogen on PDMS}PCL added PVC materials were elutability (denaturation) from (B) polyvinyl chloride (PVC), PVC#
much less than PVC controls (Fig. 1b). By correlating the 1.2% PDMS}PCL, PVC#2.4% PDMS}PCL, and PDMS after 4 h
results of surface characteristics and "brinogen adsorp- incubation. The proportion of non-elutable "brinogen was determined
using a 1% sodium dodecyl sulfate wash as described under materials
tion/denaturation, we found that silicone-like surface
and methods. Vertical lines denote $1 SD. n"5 in all cases. (Signi"cance
properties (hydrophobicity and atomic content) may vs. PVC: **P(0.01).

a!ect "brinogen:surface interactions, speci"cally the

Table 2 amounts of adsorbed and &denatured' "brinogen. It also
The shear rate vs. shear viscosity relationship of PVC and PVC blended
with di!erent concentrations (1.2 and 2.4%) of PDMS}PCL copolymer
should be noted that PDMS control surfaces adsorbed
and &denatured' more "brinogen than did PVC surfaces.
PDMS}PCL 0 1.2 2.4
(wt %)
shear rate (s-1) Shear viscosity (PA-s)
3.3. Acute inyammatory responses on implanted
test surfaces
55.9 832.9 787.5 777.6
223.4 403.5 382.0 376.6 Because adsorbed "brinogen is critical in triggering
837.8 182.1 174.5 173.2 tissue responses (speci"cally acute in#ammation and
2443.5 88.1 83.4 81.5
6981.5 39.9 38.5 37.7
chronic "brosis) to biomaterial implants, we have postu-
lated that surfaces which favor the &denaturation' of
 L. Tang et al. / Biomaterials 20 (1999) 1365}1370
Fig. 2. Phagocyte accumulation on the surfaces of PVC, PDMS}PCL
blended PVC (PVC#1.2% PP and PVC#2.4% PP), and PDMS
surfaces after implantation in SW mice for 16 h. Error bars denote
$1 SD (n"4 in all groups). (Signi"cance vs. PVC implants: *P(0.05
and **P(0.01). The numbers of adherent PMN and macro-
phages/monocytes were estimated by the activities of implant-asso-
ciated peroxidase and non-speci"c esterase, respectively (as described
under materials and methods). Measured implant-associated per-
oxidase activities (mUnit/cm): 4.90$1.99 on PVC surfaces, 1.25$
0.83 on PVC$1.2% PDMS}PCL surfaces, 0.60$0.27 on PVC$2.4%
PCL and 0.13$0.07 on PDMS surfaces. Measured implant-associated
non-speci"c esterase activities (mUnit/cm): 1.51$0.51 on PVC
surfaces, 0.70$0.32 on PVC$1.2% PDMS}PCL surfaces, 0.44$0.21
on PVC$2.4% PCL and 0.15$0.08 on PDMS surfaces.
"brinogen may prompt stronger tissue responses to bio-
material implants [50]. Based on this hypothesis, one
might predict that PDMS}PCL-supplemented PVC
prompts lesser in#ammatory responses to implanted bio-
materials than do PVC controls. Although PDMS adsor-
bed and &denatured' "brinogen, due to the high-chain
#exibility, PDMS surfaces are known to discourage cell
adhesion.
To determine tissue responses to di!erent materials,
a mouse peritoneal implantation model was used. We
and others have shown that the peritoneal cavity is
a good implantation site for studying biomaterial:tissue
interactions, because the reactions elicited by implanted
materials are clearly de"ned with minimal participation
of the coagulation system [41}43, 51}54]. Di!erent sur-
faces were implanted in mouse peritonea for 16 h. By
analyzing the explants, we found that these test surfaces
triggered di!ering degrees of in#ammatory responses,
re#ected by the numbers of phagocytes (both neutrophils
and M ) associated with material surfaces. First, as ex-
pected, PVC surfaces trigger the strongest in#ammatory
responses while PDMS surfaces prompt the least phago-
cyte responses. Second and most importantly, with in-
creasing concentrations of siloxane copolymer, the
PDMS}PCL-blended surfaces decrease their tendencies
to prompt in#ammatory responses (Fig. 2).
1369
4. Conclusions
Overall, the present work supports the idea that the
addition of PDMS}PCL block copolymer may not only
modify substrate materials with silicone-like surface
properties, but also improve the biocompatibility of sub-
strate materials, at least polyvinyl chloride. Finally, our
foregoing results support our hypothesis that supplement
of 2.4% PDMS}PCL modi"es surface properties su$-
ciently to in#uence tissue responses to the substrate ma-
terials.
Acknowledgements
We are pleased to acknowledge the AHA (grant-in-aid
95007220), NIH (RO1-HL53637 and RO1-HL56187)
and the Texas Advanced Technology Program (grant
004949-010) for partial support of this work.
References
[1] Coleman RW. Surface-mediated defense reactions. The plasma
contact activation system. J Clin Invest 1984;73:1249}53.
[2] Yates SG II, Nakagawa Y, Berger K, Sauvage LR. Surface throm-
bogenicity of arterial prostheses. Surg Gynec Obstet
1973;136:12}6.
[3] Cappelli G, Lucchi L, Bonucchi D, Cenci AM, Montagnani G,
Palma MD, Lusvargh E. Polymorphonuclear oxygen free radical
production and complement activation induced by dialysis mem-
branes as assayed in an experimental model. Blood Purif
1989;7:293}300.
[4] Gobel RJ, Janatova J, Googe JM, Apple DJ. Activation of com-
plement in human serum by some synthetic polymers used for
intraocular lenses. Biomaterials 1987;8:285}8.
[5] Kottke-Marchant K, Anderson JM, Miller KM, Marchant RE,
Lazarus H. Vascular graft-associated complement activation and
leukocyte adhesion in an arti"cial circulation. J Biomed Mater
Res 1987;21:379}97.
[6] Shepard AD, Gelfand JA, Callow AD, O'Donnell TF Jr. Com-
plement activation by synthetic vascular prostheses. J Vasc Surg
1984;1:829}38.
[7] Nusbacher J, Rosefeld SI, MacPherson JL, Thiem PA, Leddyu
JP. Nylon "bre leukapheresis: associated complement component
changes and granulocytopenia. Blood 1978;51:359}65.
[8] Craddock PR, Fehr J, Dalmasso AP, Brigham KL, Jacob HS.
Hemodialysis leukopenia. J Clin Invest 1977;59:879}88.
[9] Marchant RE, Hiltner A, Hamlin C, Rabinovitch A, Slobodkin R,
Anderson JM. In vivo biocompatibility studies: I. the cage im-
plant system and a biodegradable hydrogel. J Biomed Mater Res
1983;17:301}25.
[10] Marchant RE, Miller KM, Anderson JM. In vivo biocompatibil-
ity studies: V. In vivo leukocyte interactions with biomer. J Bio-
med Mater Res 1984;18:1169}90.
[11] Marchant RE, Anderson JM, Dillingham EO. In vivo biocom-
patibility studies: VII. In#ammatory response to polyethylene
and to a cytotoxic polyvinylchloride. J Biomed Mater Res
1986;20:37}50.
[12] Jansen B, Peters G, Bulverer G. Mechanisms and clinical rel-
evance of bacterial adhesion to polymers. J Biomater Applica-
tions 1988;2:520}43.
1370 L. Tang et al. / Biomaterials 20 (1999) 1365}1370
[13] Gristina AG. Biomaterial-centered infection: microbial adhesion
versus tissue integration. Science 1987;237:1588}95.
[14] Lew DP. Physiopathology of foreign body infections. Eur J Can-
cer Clin Oncol 1989;25:1379}82.
[15] Dekker A, Reitsma K, Beugeling T, Bantjes A, Feijen J, van Aken
WG. Adhesion of endothelial cells and adsorption of serum pro-
teins on gas plasma-treated polytetra#uoroethylene. Biomaterials
1991;12:130}8.
[16] Ko TM, Lon JC, Cooper SL. Surface characterization and plate-
let adhesion studies of plasma-sulphonated polyethylene. Bio-
materials 1993;14:657}64.
[17] Ko TM, Cooper SL. Surface properties and platelet adhesion
characteristics of acrylic acid and allylamine plasma-treated poly-
ethylene. J Appl Polym Sci 1993;47:1601}19.
[18] Sano S, Kato K, Ikada Y. Introduction of functional groups onto
the surface of polyethylene for protein immobilization. Bio-
materials 1993;14:817}22.
[19] Lee JH, Park JW, Lee HB. Cell adhesion and growth on polymer
surfaces with hydroxyl groups prepared by water vapor plasma
treatment. Biomaterials 1991;12:443}8.
[20] Lee JH, Jung HW, Kang IK, Lee HB. Cell behavior on polymer
surfaces with di!erent functional groups. Biomaterials
1994;15:705}11.
[21] Lyman DJ, Metcalf LC, Albo D Jr, Richards KF, Lamb J. The
e!ect of chemical structure and surface properties of synthetic
polymers on the coagulation of blood. III. In vivo adsorption of
proteins on polymer surfaces. Trans ASAIO 1974;20:474}9.
[22] Brash JL. Hydrophobic polymer surfaces and their interactions
with blood. Ann NY Acad Sci 1977;283:356}71.
[23] Leininger RI, Falb RD, Grode GA. Blood-compatible plastics.
Ann NY Acad Sci 1968;146:11}20.
[24] Yilgor I, Steckle WP Jr, Yilgor E, Freelin RG, Ri%e JS. Novel
triblock siloxane characterization, and their use as surface
modifying additives. J Polym Sci Part A: Polym Chem 1989;27:
3673}90.
[25] Noll W. Chemistry and technology of silicons. New York: Aca-
demic Press, 1968.
[26] Noshay A, McGrath AE. Block copolymer: overview and critical
survey. New York: Academic Press, 1977.
[27] Lelah MD, Cooper SL. Polyurethane in Medicine. Boca Raton:
CRC Press, 1986.
[28] Kawakami Y, Yamashita Y. Ring-opening polymerization. In:
McGrath JE, editor, ACS symposium series No. 286, Washington
DC: American Chemical Society, Washington, 1985 [Chapter 19].
[29] Voronkov MG, Mileshkevich VP, Yuzhelevskii YA. The siloxane
bond. New York: Consultants Bureau, 1978.
[30] Yilgor I, McGrath JE. Advances in polymer science: polysiloxane
copolymers/anionic polymerization. Berlin: Springer, 1988:1}86.
[31] Zisman WA, Jarvis NL, Fox RB. Vinyl polymers modi"ed with
#uoro esters. US Patent 3356632, 1967.
[32] Kumaki T, Sisido M, Imanishi Y. Antithrobogenicity and oxygen
permeability of block and graft copolymers of polydimethyl-
siloxane and poly(a-amino acid). J Biomed Mater Res 1985;19:
785}811.
[33] Walters K. Rheometry: industrial applications. Chichester, Eng-
land: Research Studies Press, 1980.
[34] Van Wazer JR, Lycons JW, Kim KY, Colwell RE. Viscosity and
#ow measurement: a laboratory handbook of rheology. New
York: Interscience, 1963.
[35] Dealy JM. Rheometers for Molten Plastics. New York: Van
Norstrand Reinhold, 1982.
[36] Rauwendaal C. Polymer extrusion. Munich: Carl Hanser Verlag,
1986.
[37] Sheu MS, Hudson DM, Loh IH. Biomaterial surface modi"ca-
tion using plasma gas discharge processes. In: Wise DL, Trantolo
DL, Altobelli DE, Yaszemski MJ, Gresser JD, Schwartz ER,
editors. Vol. 1, Part A: Materials. New York: Marcel Dekker,
1996:865}94.
[38] Ratner BD, Castner DG, Horbett TA, Lenk TJ, Lewis KB,
Rapoza RJ. Biomolecules and surfaces. J Vasc Sci Tech 1990;8:
2306}16.
[39] Bohnert JL, Horbett TA. Changes in adsorbed "brinogen and
albumin interactions with polymers indicated by decreases in
detergent elutability. J Colloid Interface Sci 1986;111:363}77.
[40] Chinn JA, Posso SE, Horbett TA, Ratner BD. Postadsorptive
transitions in "brinogen adsorbed to polyurethanes: changes in
antibody binding, and sodium dodecyl sulfate elutability. J Bio-
med Mater Res 1992;26:757}78.
[41] Tang L, Eaton JW. Fibrin(ogen) mediates acute in#ammatory
responses to biomaterials. J Exp Med 1993;178:2147}56.
[42] Tang L, Lucas AH, Eaton JW. In#ammatory responses to Dac-
ron: role of surface adsorbed IgG. J Lab Clin Med 1993;122:
292}300.
[43] Tang L, Ugarova TP, Plow EF, Eaton JW. Molecular determi-
nants of acute in#ammatory responses to biomaterials. J Clin
Invest 1996;97:1329}34.
[44] Pitt WG, Park K, Cooper SL. Sequential protein adsorption and
thrombus deposition on polymeric biomaterials. J Colloid Inter-
face Sci 1986;111:343}62.
[45] Anderson JM, Bon"eld TL, Ziats NP. Protein adsorption and
cellular adhesion and activation on biomedical polymers. Int
J Artif Organs 1990;13:375}82.
[46] Sevastianov VL. Role of protein adsorption in blood compatibil-
ity of polymer. CRC Crit Rev Biocompat 1988;4:109}54.
[47] Roohk HV, Nakamura M, Hill RL, Hung EK, Bartlett RH.
A thrombogenic index for blood contact materials. Trans ASAIO
1977;23:152}61.
[48] Whicher SJ, Brash JL. Platelet-foreign surface interactions: re-
lease of granule constituents from adherent platelets. J Biomed
Mater Res 1978;12:181}90.
[49] Horbett TA, Cheng CM, Ratner BD, Ho!man AS, Hanson SR.
The kinetics of baboon "brinogen adsorption to polymers:
In vitro and in vivo studies. J Biomed Mater Res 1986;20:739}72.
[50] Tang L, Wu Y-L, Timmons RB. Biomaterial surface properties
a!ecting both protein adsorption and host tissue responses. J Bio-
med Materials Res 1998;42:156}63.
[51] Freyria AM, Chignier E, Guidollet J, Louisot P. Peritoneal mac-
rophage response: an in vivo model for the study of synthetic
materials. Biomaterials 1991;12:111}8.
[52] Merhi Y, Roy R, Guidoin R, Hebert J, Mourad W, Benslimane S.
Cellular reactions to polyester arterial prostheses impregnated
with cross-linked albumin; In vivo studies in mice. Biomaterials
1989;10:56}8.
[53] Uenoyama K, Kanagawa R, Tamura M, Matoba M, Enomoto Y,
Ohmi S. Experimental intraocular lens implantation in the rabbit
eye and in the mouse peritoneal space. Part 1. Cellular compo-
nents observed on the implanted lens surface. J Cataract Refract
Surg 1988;14:187}91.
[54] Christenson L, Aebischer P, McMillan P, Galletti PM. Tissue
reaction to intraperitoneal polymer implants, species di!erence
and e!ects of corticoids and doxorubicin. J Biomed Mater Res
1989;23:705}18.