FULL PAPER
Synthesis of a Novel, Biodegradable Electrically Conducting
Polymer for Biomedical Applications**
By Tyrell J. Rivers, Terry W. Hudson, and Christine E. Schmidt*
We report the synthesis and characterization of a novel biomaterial that possesses the unique properties of being both electri-
cally conducting and biodegradable; and thus capable of electronic interfacing with tissue. This polymer was synthesized from
conducting oligomers of pyrrole and thiophene that are connected together via degradable ester linkages. We demonstrate that
this polymer is conductive, degradable, and biocompatible.
1. Introduction
The next generation of implantable biomaterials will be in-
teractive and programmable, and thus capable of seamless
communication with surrounding tissues. Specifically, materials
that incorporate stimulatory cues, such as electrical signals, can
be used to regulate cell attachment, proliferation, and differen-
tiation. For example, electrical fields have been shown to stim-
ulate the healing of bone,[1] cartilage,[2] skin and connective
tissue,[3] cranial and spinal nerves,[4] and peripheral nerves.[5]
To take advantage of these effects, researchers have sought to
incorporate electrical signals directly into biomaterials. The use
of electroactive materials would allow one to locally deliver an
electrical stimulus at the site of damage, while also providing a
physical template for cell growth and tissue repair.
To this end, polymers have been processed to display perma-
nent charges (electrets) or to generate transient surface charges
(piezoelectric materials). Studies using these materials have
demonstrated enhancement of nerve and bone cell growth in
vitro and in vivo.[6] Another class of electroactive polymers is
the class of electrically conducting polymers, which includes
polypyrrole and polythiophene. In contrast to electrets and
piezoelectric materials, polypyrrole and polythiophene gener-
ate electrical signals by electron transfer between different
polymer chains. In-vitro enhancement of nerve cell axonal ex-
tension has been reported using polypyrrole with application of
either constant current or constant voltage.[7] Polypyrrole has
also been used as a substrate to increase electronic interfacing
between neurons and micromachined microelectrodes for po-
tential applications in neural probes and prosthetic devices.[8]
± mer of three units because synthetic procedures for oligomers
[*] Dr. C. E. Schmidt, T. J. Rivers, T. W. Hudson
Department of Chemical Engineering
Texas Materials Institute and Biomedical Engineering
The University of Texas at Austin
26th and Speedway, MC C0400, Austin, TX 78712-1062 (USA)
E-mail: schmidt@che.utexas.edu
[**] The authors thank Robert Langer and Prasad Shastri for early contribu-
tions and insight, Grant Willson and Jonathon Sessler for feedback and
guidance, and Keith Freidman, Daniel Seidel, Kelly Wouters, Joseph Shuga,
and Gary Binyamin for technical assistance. This work was supported by an
NSF grant to CES (BES-9702882), a GEM Fellowship and NIH Training
Grant Fellowship to TJR, and an NIH Training Grant Fellowship to TWH.
Adv. Funct. Mater. 2002, 12, No. 1, January Ó WILEY-VCH Verlag GmbH, D-69469 Weinheim, 2002
Electrically conducting polymers, unlike electrets and piezo-
electric materials, allow external control over the level and
duration of stimulation, which is beneficial for biomedical
applications. Moreover, conducting polymers, in contrast to
piezoelectric materials, do not require extensive processing to
render them electroactive. These materials can also be modi-
fied with negatively charged dopant ions, which can be tailored
to specific applications. For example, polypyrrole has been
doped with biological anions such as hyaluronan, which stimu-
lates angiogenesis as it degrades,[9] and adhesive peptides,
which enhance material±cell interactions.[8] Polypyrrole and
polythiophene, however, are not degradable, and materials that
remain in the body long-term may induce chronic inflamma-
tion and require surgical removal. Thus, the use of degradable
materials in clinical applications has become attractive.[10] To
date, no biomaterial exists that possesses the properties of con-
trollable electrical stimulation and biodegradation.
To address the drawbacks of existing electroactive biomate-
rials, we have synthesized a polymer that possesses the unique
properties of being both electrically conducting and biodegrad-
able. Our synthetic strategy consisted of tethering conductive
pyrrole±thiophene oligomers together with degradable ester
linkages using an aliphatic linker (Fig. 1A). Oligomers of these
conducting polymers were selected because: i) oligomers of
thiophene possess electrical properties;[11] ii) defects in the
p-conjugation of polypyrrole are present in frequencies of one
defect per three pyrrole rings, suggesting that intact polypyr-
role is not essential for conductivity and that oligomers are suf-
ficient;[12] and iii) after polymer degradation, the remaining
oligomers should be readily consumed by macrophages during
the normal wound healing response, reducing chances of long-
term, adverse responses.[13] Specifically, we selected an oligo-
of this length are reported.[14] We initially designed our poly-
mer with a three-pyrrole oligomer, based on our own previous
studies with polypyrrole. However, we found it necessary to
introduce a thiophene to add stability to the oligomer during
synthesis. Ester linkages were chosen for degradation sites
because they can be cleaved by enzymes, such as cholesterol
esterase, which are secreted by cells during normal wound
repair processes. Finally, we selected an aliphatic linker to
impart flexibility to the polymer.
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 T. J. Rivers et al./Biodegradable Electrically Conducting Polymer for Biomedical Applications
FULL PAPER

which precipitated from the cooled reaction mixture in 87 %

yield. Closure of 4 to the corresponding thiophene ring (5) was
performed using Lawesson's reagent in refluxing toluene and
subsequent base hydrolysis of the methyl ester groups provided
6. Compound 6 was esterified to 7 using 1,8-diazabicy-
clo[5.4.0]undecene-7 (DBU) and 3-bromo-1-propanol in di-
methyl sulfoxide (DMSO). BECP (8) was prepared in 60 %
yield by condensation of 7 with adipoyl chloride in refluxing
pyridine.
Nuclear magnetic resonance (NMR) analysis was used to
confirm the successful synthesis of the polymer and to ensure
that the aromatic segment was unaltered in the polymerization.
This confirmation is important because the aromatic unit will
confer conductivity to the biomaterial upon oxidation. There-
fore, comparing the proton NMR spectra of the monomer (7;
Fig. 2A) and BECP (8; Fig. 2B) revealed conservation of the
aromatic oligomer as indicated by the presence of peaks a, b,

Fig. 1. Structure and synthetic reaction scheme for biodegradable, electrically

conducting polymer (BECP). A) Schematic of BECP illustrating its key compo-
nents: a conducting pyrrole±thiophene±pyrrole oligomer, degradable ester link-
ages, and an aliphatic linker. B) Reaction scheme for the synthesis of BECP 8.
Synthetic details are found in the text. Reaction conditions: a) Cl3COCl;
b) methanol, Na, reflux; c) i) POCl3, dimethylformamide (DMF); ii) NaHCO3;
d) thiazolium salt catalyst, NaOAc, divinyl sulfone, EtOH reflux; e) Lawesson's
reagent, toluene, reflux; f) NaOH, MeOH, H2O, reflux; g) DBU, 3-bromo-1-pro-
panol, DMF; h) adipoyl chloride, pyridine, reflux.

The aim of this work was to demonstrate the feasibility of

creating a biodegradable, electrically conducting polymer.
Once this proof-of-principle has been established, polymer
optimizations can be performed, e.g., increasing the aromatic
segment length to enhance conductivity, altering the hydropho-
bic/hydrophilic nature of the linker to modulate degradation,
and incorporating sites for attachment of biomolecules that
evoke desired cellular responses.

2. Results and Discussion

Synthesis of our biodegradable electrically conducting poly-

mer (BECP) 8 is outlined in Figure 1B. This was accomplished,
in part, using modifications of reported procedures.[14a,15] Pyr-
role was treated with trichloroacetyl chloride in ether to give 1.
The methyl ester (2) of compound 1 was formed in a reaction
with sodium methoxide in refluxing methanol. The 5-position
of 2 was formylated using Vilsmeyer conditions to form 3. Sub-
mission of 3 to Stetter conditions resulted in the 1,4-diketone 4,
Fig. 2. Confirmation of BECP synthesis using 1H NMR. Proton NMR spectra
(d6-DMSO, 300 MHz) of A) monomer 7 and B) BECP 8 confirmed the synthesis
of these compounds and as well demonstrated conservation of the aromatic
oligomer (peaks a, b, and c). Note: The peaks are denoted by letters that corre-
spond to the labeled hydrogens on the chemical structures for the monomer and
BECP. The peak assignments were confirmed by NMR modeling software from
Advanced Chemistry Development.

34 Ó WILEY-VCH Verlag GmbH, D-69469 Weinheim, 2002 1616-301X/02/0101-0034 $ 17.50+.50/0 Adv. Funct. Mater. 2002, 12, No. 1, January
T. J. Rivers et al./Biodegradable Electrically Conducting Polymer for Biomedical Applications
and c, belonging to the b-position hydrogens on this oligomeric
unit. In addition, UV-vis spectra of the monomer and BECP
were essentially identical with absorption maxima at 375 nm in
tetrahydrofuran (THF), demonstrating the preservation of the
aromatic region. Synthesis of BECP was further confirmed
using carbon-NMR, infrared spectroscopy (IR), and X-ray
photoelectron spectroscopy (XPS) (not shown).
General polymer characterization was also performed. The
weight average molecular weight and polydispersity index of
BECP were determined to be 8500 and 3.0, respectively, using
gel permeation chromatography (GPC) with polystyrene as a
reference. Furthermore, the hydrophilicity of the polymer was
measured since it is well known that this property will influ-
ence protein adsorption and cell attachment. The internal
water contact angle on BECP was determined to be 77 ± 2
(mean ± standard deviation; n = 47). Studies have shown that
contact angles in the range of 40±80 maximize the adhesion
of multiple cell types.[16]
Electrical activity of our polymer is essential for the stimula-
tion of responsive cells. To test for conductivity, BECP polymer
films were cast, connected to copper wires using carbon paste,
and oxidized to their conductive form by doping with iodine
vapor. The resistance of the oxidized BECP films was mea-
sured using a potentiostat and the conductivity was calculated
as described.[9] BECP conductivity was found to be on the
order of 10±4 S/cm (n = 3). For comparison, polypyrrole has a
conductivity that ranges from 1±100 S/cm,[17] depending on the
dopant, and semiconductor materials such as silicon and ger-
manium have values that range from 10±5±102 S/cm. Although
BECP has a conductivity comparable to that of semiconduc-
tors, we are modifying BECP with longer aromatic segments to
increase conductivity. In addition, we are exploring other oxi-
dation methods (chemical and electrochemical) to render
BECP conductive without the use of iodine vapor. In the
meantime, all studies, besides the conductivity tests, were per-
formed on non-oxidized BECP to demonstrate general proper-
ties of the base polymer.
The critical feature of BECP is its ability to degrade. Ester
linkages, as found in BECP, are known to be biodegradable;
however, the composition of the polymer may have a significant
effect on degradation. Thus, we confirmed that the ester groups
of BECP could be hydrolyzed under representative biological
conditions. Films of BECP were incubated with and without
cholesterol esterase in phosphate-buffered saline (PBS) at
37 C. After 2 weeks, degradation products were found in the
supernatant of solutions containing BECP, PBS, and esterase,
but not in the supernatant of solutions containing BECP and
PBS only, as determined by UV-vis analyses (Fig. 3). This result
demonstrates that BECP is in fact biodegradable, and specifi-
cally, it is subject to degradation by enzymes naturally found in
the body. In addition, GPC analysis showed that the bulk
polymer molecular weight was unchanged, suggesting that deg-
radation occurs at the polymer±solution interface and pro-
gresses inward over time (i.e., ªsurface erosionº).
It is essential that our polymer be non-toxic to biological
systems and able to support cell growth if it will be used as an
implantable biomaterial. To assess cell compatibility, human
Adv. Funct. Mater. 2002, 12, No. 1, January Ó WILEY-VCH Verlag GmbH, D-69469 Weinheim, 2002
FULL PAPER
Fig. 3. Biodegradation of BECP. Degradation studies of BECP films (3.0 cm ”
2.2 cm ” ~2.0 mm) were performed in PBS with and without cholesterol esterase
for 2 weeks. The supernatants of the solutions were evaluated by measurement
of their UV-vis absorption. The aromatic rings found in the polymer and in the
degraded species absorb preferentially at a wavelength of 340 nm (arrow) in PBS
and the esterase absorbs at 280 nm (arrowhead). The supernatant of the polymer
+ esterase shows a strong absorption peak at 340 nm compared to the superna-
tant of the polymer without the esterase. This demonstrates that BECP is degrad-
able by enzymes which are known to be secreted during in-vivo wound healing
events. Note: The y-axis is reported in absorbance units (a.u.).
neuroblastoma cells (central nervous system neurons) were
seeded onto thin BECP films (n = 3). We used nerve cells be-
cause they depend strongly on favorable cell±surface interac-
tions in order to express their neural phenotype; therefore,
nerve cultures provide a good measure of compatibility. Cells
adhered to BECP and readily expressed their nerve-like phe-
notype by extending neurites after one day (Fig. 4A, left).
After 8 days, significant cell proliferation was observed
(Fig. 4A, right). These data demonstrate that in addition to
being non-toxic to cells in culture, BECP can also support cell
attachment and proliferation.
In-vivo biocompatibility of BECP was characterized by sub-
cutaneous implantation into rats for 14 and 29 days using Food
and Drug Administration (FDA)-approved poly(lactic-co-gly-
colic) acid (PLGA) as a control (BECP: n = 8 and PLGA: n = 4,
for each time point). A comparison of the tissue±polymer inter-
face for BECP and PLGA implants (Fig. 4B, left and right, re-
spectively) shows that inflammation around BECP is mild and
similar to that seen with PLGA at 29 days. In addition, native
dermal tissue is found just beyond the encapsulating layer at the
tissue±polymer interface. In-vivo analysis also demonstrated
degradation of BECP as evidenced by a significant increase in
the infiltration of tissue between polymer fragments from 14 to
29 days (not shown). Thus, there appears to be no detectable
toxic effect of the base material or its degraded products in vivo.
3. Conclusions
We have described the synthesis and characterization of a
novel biodegradable, electrically conducting polymer that dem-
onstrates good tissue compatibility. This material has broad
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 T. J. Rivers et al./Biodegradable Electrically Conducting Polymer for Biomedical Applications
FULL PAPER
Fig. 4. Biocompatibility assessment of BECP. A) Human neuroblastoma cells
cultured in vitro on BECP films demonstrated attachment and neurite extension
after 1 day (left) and significant proliferation after 8 days (right), indicating good
cell compatibility. Images are phase contrast micrographs obtained with a 10” air
objective. Both images are at the same magnification. Scale bar = 100 lm.
B) BECP and FDA-approved PLGA (control) were implanted subcutaneously
in rats to assess in-vivo compatibility. Histological tissue sections (stained with
hematoxylin and eosin) of implanted BECP (left) and PLGA (right) demonstrat-
ed comparably low inflammatory responses at 29 days. Arrowheads depict the
encapsulating layer at the tissue±polymer interface. The polymers are not readily
visualized in the images; BECP and PLGA were extracted with histological pro-
cessing. A few remnants of BECP are found at the interface (faint structures at
the interface, two are indicated by arrows) (image on left). Images are brightfield
micrographs obtained with a 60” oil-immersion objective. Both images are at the
same magnification. Scale bar = 50 lm.
potential for i) tissue engineering applications as a temporary
scaffold for cell attachment and as a source of electrical signals
to stimulate tissue regeneration and ii) bioelectronic applica-
tions in which a transient electronic±tissue interface is desired.
This work illustrates one step toward the next generation of
biomaterials that will be capable of intimate electronic and bio-
logical interfacing with cells and tissues.
4. Experimental
1
H NMR and 13C NMR spectra were obtained using a Varian Ultra Plus spec-
trometer (300 MHz and 75 MHz, respectively). Reagents and solvents were from
Aldrich and used as received unless noted. Toluene and THF were dried by
refluxing with sodium benzophenone ketyl under nitrogen. Pyridine and dichlo-
roethane were dried by distillation under nitrogen from calcium hydride and
stored over 4 Š molecular sieves. Pyrrole and phosphorus oxychloride were puri-
fied by distillation under nitrogen before use.
2-(Trichloroacetyl)pyrrole (1) and methyl-pyrrole-2-carboxylate (2): These
compounds were prepared as described previously [15]. However, the synthesis
of 2 required that ethanol be replaced by methanol. 1H NMR of 1: (CDCl3): d
[ppm] 9.65 (br s, 1H), 7.40 (m, 1H), 7.18 (m, 1H), 6.39 (dd, 1H). 1H NMR of 2:
(CDCl3): d [ppm] 7.00 (m, 1H), 6.79 (d, 1H), 6.15 (dd, 1H), 3.74 (s, 1H).
Methyl-5-formylpyrrole-2-carboxylate (3): Compound 3 was prepared as de-
scribed [15]. However, the crude solid obtained was sublimed at 20 ” 10±3 torr
and 60 C in 3 h intervals to yield 3 (7.79 g, 50.1 mmol, 66 %). 1H NMR (CDCl3):
d [ppm] 10.57 (br s, 1H), 9.70 (s, 1H), 6.95 (m, 2H), 3.94 (s, 3H).
1,4-Bis(5-(methoxycarbonyl)-2-pyrryl)-1,4-butanedione (4): A modified proce-
dure of [14a] was used. A mixture of methyl-5-formylpyrrole-2-carboxylate (3,
4.59 g, 30.0 mmol), 3-benzyl-5-(2-hydroxyethyl)-4-methyl-1,3-thiazolium chlo-
ride (1.23 g, 4.6 mmol), NaOAc (0.63 g, 7.7 mmol), and ethanol (40 mL) was
heated to reflux under argon. Divinyl sulfone (1.76 g, 14.9 mmol) was added
dropwise and the mixture was refluxed for 17 h. The precipitate was filtered and
washed with ethanol, water, and Et2O. A yellowish white solid was obtained
(4.49 g, 13.5 mmol, 90 %). 1H NMR (d6-DMSO): d [ppm] 7.05 (m, 1H), 6.85 (m,
36 Ó WILEY-VCH Verlag GmbH, D-69469 Weinheim, 2002 1616-301X/02/0101-0036 $ 17.50+.50/0
1H), 3.79 (s, 3H), 3.21 (s, 2H). 13C NMR: d [ppm] 189.4, 160.5, 134.9, 126.7, 115.7,
115.4, 51.7, 32.2.
2,5-Bis(5-(methoxycarbonyl)-2-pyrryl)thiophene (5): A modified procedure of
[14a] was used. A mixture of 4 (1.73 g, 5.2 mmol), dry toluene (75 mL), and Law-
esson's reagent (1.50 g, 3.7 mmol) was refluxed under argon for 12 h. The solu-
tion was cooled to room temperature (RT) and solvent was removed in vacuo.
Column chromatography (silica gel; 230±400 mesh) of the crude solid was
performed using dichloromethane. Conversion to a 50:50 hexane/ethyl acetate
eluent system yielded 0.86 g (2.6 mmol, 50 %) of a yellow solid. 1H NMR
(d6-DMSO): d [ppm] 7.70 (s, 1H), 6.96 (dd, 1H), 6.52 (dd, 1H), 3.93 (s, 3H). 13C
NMR: d [ppm] 161.8, 134.0, 132.4, 125.7, 124.0, 117.8, 109.2, 52.2.
2,5-Bis(5-(hydroxycarbonyl)-2-pyrryl)thiophene (6): A mixture of 5 (1.56 g,
4.73 mmol), methanol (125 mL), NaOH (30 g), and water (80 mL) was refluxed.
The reaction was cooled to RT and methanol was removed in vacuo. The mixture
was poured into ice water and acidified slowly using 1 M HCl until precipitation
resulted. Filtration and drying produced 1.29 g (4.3 mmol, 90 %) of the green
title compound. 1H NMR (d6-DMSO): d [ppm] 7.33 (s, 1H), 6.81 (dd, 1H), 6.37
(dd, 1H). 13C NMR: d [ppm] 162.2, 134.6, 132.0, 125.1, 124.4, 117.1, 108.8.
2,5-Bis-(5-(3-hydroxypropoxycarbonyl)-2-pyrrolyl)thiophene (7): DBU (1.29 g,
8.46 mmol) was added dropwise over 10 min to a stirred solution of 6 (1.28 g;
4.23 mmol) in anhydrous DMSO (20 mL) under nitrogen. After stirring for 20 min,
1.77 g (12.70 mmol) of 3-bromo-1-propanol was added dropwise over 10 min and
stirring was continued overnight at RT. The mixture was poured into water and
precipitate was collected by filtration and washed with water. Crude product was
purified by chromatography (silica gel; 230±400 mesh; 30:70 hexanes/ethyl acetate)
to yield 7 (1.08 g, 2.58 mmol, 61 %). 1H NMR (d6-DMSO): d [ppm] 12.26 (s, 1H),
7.56 (s, 1H), 6.80 (d, 1H), 6.39 (d, 1 H), 4.56 (s, 1H), 4.27 (d, 2H), 3.52 (d, 2H), 1.82
(m, 2H). 13C NMR: d [ppm] 160.38, 132.91, 131.21, 124.70, 123.21, 116.72, 108.28,
61.24, 57.42, 31.86.
Synthesis of BECP (8): Adipoyl chloride (0.525 g, 2.87 mmol) in anhydrous
THF (2 mL) was added to a solution of 7 (1.20 g, 2.87 mmol) in dry pyridine
(20 mL) under nitrogen. The solution was refluxed overnight and pyridine was
evaporated in vacuo. Water was added and the solid was collected by filtration.
After washing with water, the solid was added to boiling methanol, filtered, and
dried to yield 0.89 g (1.72 mmol; 60 %) of the polymer. 1H NMR (d6-DMSO): d
[ppm] 12.22, 7.54, 6.81, 6.39, 4.26, 4.13, 2.25, 1.97, 1.48. 13C NMR: d [ppm] 172.76,
160.15, 132.89, 131.31, 124.72, 122.97, 116.87, 108.28, 60.96, 60.74, 33.11, 27.86, 23.88.
Physical Characterization: UV-vis spectra were recorded on a Beckman DU
530 spectrophotometer using a 1 cm path cell. GPC measurements to assess mo-
lecular weight and polydispersity index were performed in THF using a Viscotek
Model 250 refractometer, a Waters 515 high-pressure liquid chromatography
(HPLC) pump, and two columns (10M-mixed-B-98A-6, Polymer Laboratories).
To measure the contact angle, polymer films were spin-coated at 7000 rpm onto
a glass slide using a Pine Instruments Rotator. Films were vacuum rinsed with de-
ionized, distilled water (DDW). Contact angles were obtained using a Rame-hart
goniometer Model 100-00 with DDW. Approximately 12 measurements were
taken for each of four drops.
Conductivity Measurements: To prepare BECP films and measure their con-
ductivity, a solution of polymer in THF (~0.1 g/mL) was dropped onto the center
of a glass slide (2.5 cm ” 2.5 cm) while rotating at 5000±10 000 rpm (Photo-Resist
Spinner model #1-EC101I-R485, Headway Research Inc. controller). Four cop-
per wires were attached to the polymer edges using carbon paste and solder. This
assembly was suspended, film facing down, in a sealed jar with iodine crystals.
The crystals were heated to produce vapor and allowed to cool to RT for 30 min.
Measurements were made using the four-point probe technique [9]. The voltage
was measured using an A. W. Sperry DM-8A multimeter. A Fluke instruments
5100B calibrator served as the current source. The film thickness was measured
using a Tencor Instrument Alphastep 200 thickness measurement tool.
In-Vitro Biodegradation Studies: BECP films (3.0 cm ” 2.2 cm ” ~2 mm) were
prepared by evaporating the polymer (in DMSO) on a glass slide at 50 C. After
drying, films were removed from the slide and incubated in 1.5 mL of PBS
(pH 7.0) at 37 C while rotating. The PBS was replaced after 24 h with either
1.5 mL of fresh PBS or with cholesterol esterase (100 units in 1.5 mL of PBS;
Sigma). Samples were rotated at 37 C for 2 weeks. The supernatant was used for
UV-vis analysis and the polymer was used in GPC analysis.
In-Vitro Cell Compatibility Studies: BECP films were prepared in the same
manner as for conductivity studies. Films were vacuum dried and soaked in
DDW overnight. Polycarbonate wells (1.5 cm ” 1.0 cm, inside area) were at-
tached to BECP films using silicone rubber and vacuum dried. These were
rinsed with DDW and UV sterilized for 1.5 h. Human neuroblastoma cells
(SK-N-SH, American Type Culture Collection) were seeded on the polymer in
Eagle's minimum essential medium (EMEM) with 2 mM L-glutamine, Earles's
balanced salt solution, 1.5 g/L sodium bicarbonate, 0.1 mM non-essential ami-
no acids, 1.0 mM sodium pyruvate, and 10 % fetal bovine serum (FBS). Re-
agents were from Sigma except for FBS (Hyclone). These wells were placed in
sterile petri dishes and cultured at 37 C, 5 % CO2. Phase-contrast images were
captured with an Olympus IX70 inverted microscope and an Optronics Mag-
nafire camera (Model S60800).
Adv. Funct. Mater. 2002, 12, No. 1, January
T. J. Rivers et al./Biodegradable Electrically Conducting Polymer for Biomedical Applications
In-Vivo Biocompatibility Studies: BECP films (3.0 cm ” 2.2 cm ” ~2 mm)
were cast on glass slides from DMSO at 50 C, and dried in vacuo at 50 C. Films
were soaked in DDW for 24 h and dried. BECP was removed from the slide, sec-
tioned into pieces (~5 mm ” 3 mm), and sterilized with UV for 45 min. Films of
PLGA (85:15, Birmingham Polymers, Birmingham, AL) were cast from dichloro-
methane in 50 mL beakers and dried overnight. PLGA was removed and cut into
pieces and sterilized as described above.
Surgical methods were in accordance with the National Institutes of Health
(NIH) guidelines for the care and use of laboratory animals (NIH Publication
85-23 Rev. 1985). Male Sprague-Dawley rats (~300 g) were anesthetized by iso-
fluorane inhalation and intraperitoneal injections of ketamine (0.28 mL) and
xylazine (0.18 mL). Areas of incision were shaved, cleaned with 70 % ethanol,
and sterilized with Betadine. All reagents, except ethanol (Sigma), were obtained
from J. A. Webster. Each rat (n = 8) received two samples of BECP and one sam-
ple of PLGA in subcutaneous pouches at the base of the neck and on either side
of the spinal cord ~5 cm from the base of the neck. Wounds were closed with sur-
gical staples. At 14 days (n = 4) and 29 days (n = 4) post-implantation, polymer
and surrounding tissue were harvested, fixed with 4 % paraformaldehyde and
3 % glutaraldehyde for 2 h, and rinsed and stored in PBS. Tissue was dehydrated
in graded alcohols and xylene and embedded in paraffin. Sections (7 lm) were
cut with a microtome and stained using a standard Harris hematoxylin and eosin
protocol. Signs of inflammation and abnormal tissue response were qualitatively
assessed using brightfield microscopy (Olympus IX70 microscope, Optronics
camera).
Received: June 20, 2001
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