Biomaterials 31 (2010) 25352541

Contents lists available at ScienceDirect

Biomaterials
journal homepage: www.elsevier.com/locate/biomaterials

General functionalization route for cell adhesion on non-wetting surfaces

Sook Hee Ku a, Jungki Ryu a, Seon Ki Hong b, Haeshin Lee b, **, Chan Beum Park a, *
a

Department of Materials Science and Engineering, KAIST Institute for the BioCentury, Korea Advanced Institute of Science and Technology (KAIST),
335 Science Rd, Daejeon 305-701, Republic of Korea
b
Department of Chemistry and Graduate School of Nanoscience and Technology, KAIST Institute for the BioCentury, Korea Advanced Institute
of Science and Technology (KAIST), 335 Science Rd, Daejeon 305-701, Republic of Korea

a r t i c l e i n f o

a b s t r a c t

Article history:
Received 30 September 2009
Accepted 7 December 2009
Available online 12 January 2010

We present a versatile route for promoting cell adhesion and viability on various non-wetting surfaces,
inspired by mussel adhesion mechanism. The oxidative polymerization of dopamine, a small designer
molecule of the DOPA-K motif found in mussels, results in the formation of a poly(dopamine) ad-layer on
any material surface. We found that the poly(dopamine) coating can promote cell adhesion on any type
of material surfaces including the well-known anti-adhesive substrate, poly(tetrauoroethylene).
According to our results, mammalian cells well adhered and underwent general cell adhesion processes
(i.e., attachment to substrate, spreading, and cytoskeleton development) on poly(dopamine)-modied
surfaces, while they barely adhered and spread on unmodied non-wetting surfaces. The musselinspired surface functionalization strategy is extremely useful because it does not require the timeconsuming synthesis of complex linkers and the process is solvent-free and non-toxic. Therefore, it can
be a powerful route for converting a variety of bioinert substrates into bioactive ones.
2009 Elsevier Ltd. All rights reserved.

Keywords:
Cell adhesion
Non-wetting surfaces
Mussel adhesives
Poly(dopamine)
Surface modication

1. Introduction
Mussels can attach to various surfaces in aqueous conditions,
ranging from natural inorganic materials (e.g., rocks) and organic
materials (e.g., sh skins) to synthetic materials (e.g., Teon). Such
adhesive properties rely on the exhaustively repeated 3,4-dihydroxy-L-phenylalanine-lysine (DOPA-K) motif found in the foot
protein of mussels [14]. The DOPA-K motif reveals the fact that the
oxidative polymerization of dopamine, a small designer molecule
inspired by the DOPA-K motif, results in the formation of a poly(dopamine) ad-layer on any material surfaces [2]. In this paper,
inspired by the mussel adhesion mechanism, we report a new
bioactive surface functionalization strategy that is extremely
powerful because 1) it can convert any type of synthetic biomaterials
into bioactive materials, 2) it does not require the time-consuming
synthesis of complex linkers, and 3) the process is solvent-free and
non-toxic.
Surface properties regulate a variety of intracellular signal
cascades for cell proliferation, migration, differentiation, and
apoptosis [5,6]. Thus, engineering the surface properties (i.e., the
biointerfaces) is the most critical step in cellmaterial interactions

* Corresponding author. Tel.: 82 42 350 3340; fax: 82 42 350 3310.

** Corresponding author. Tel.: 82 42 350 2849; fax: 82 42 350 2810.
E-mail addresses: haeshin@kaist.ac.kr (H. Lee), parkcb@kaist.ac.kr (C.B. Park).
0142-9612/$ see front matter 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.biomaterials.2009.12.020

[7,8]. In general, preparing bioinert surfaces and preparing

bioactive surfaces have been the two major strategies in cell
material interactions. Bioinert (i.e., non-fouling) surfaces resist the
protein adsorption that can mediate the cell adhesion processes.
Medically, the bioinert approach can enhance blood contact
materials, in which the inert surfaces reduce the intrinsic pathway
of blood coagulation [7,9,10] and can benet orthopedic implants,
in which non-fouling properties avoid inammatory and other
adverse responses. The majority of the literatures have focused on
the surface immobilization of poly(ethylene glycol) (PEG) to acquire
such non-fouling properties [11,12]. However, accomplishing bioinert preparation with densely packed PEG molecules on surfaces
still remains a challenge that limits its practical utility. On the other
hand, bioactive surfaces have been accomplished using biomolecules (proteins, peptides, or polysaccharides) that are grafted or
physisorbed onto substrates for cell recognition. Examples include
the immobilization of natural extracellular matrix (ECM) proteins
(e.g., collagen, bronectin, laminin, etc.) or synthetic ECM mimetic
peptides (e.g., RGD, REDV, and KRSR) [1317] that play important
roles in many cellular processes [7,18]. A large variety of synthetic,
novel biomaterials often require specialized bio-activities, but the
lack of general surface functionalization method thereof challenges
further development of useful biomaterials.
Herein, we present a versatile route for promoting cell adhesion
and viability on different types of non-wetting surfaces, based on
the inspiration from mussel adhesion phenomena. We utilized

2536

S.H. Ku et al. / Biomaterials 31 (2010) 25352541

a pH-triggered, oxidative polymerization of catecholamine in an

aqueous solution, that resulted in the formation of a thin poly(dopamine) ad-layer, which was characterized by Raman
spectroscopy and water contact angle measurement. On the poly(dopamine)-coated surfaces, we observed adhesion behaviors and
viability of two different types of mammalian cell lines, MC3T3-E1
and PC12, which have been widely used for the regeneration of bone
[19,20] and nerve tissues [21,22], respectively. We further investigated whether the cells undergo the general cell adhesion processes
of attachment, spreading, and cytoskeleton development on the
poly(dopamine)-coated surfaces.
2. Materials and methods
2.1. Substrate preparation and poly(dopamine) coating
Glass (Marlenfeld GmbH, Germany), poly(dimethylsiloxane) (Sylgard 184, Dow
Corning, MI, U.S.A), silicone rubber (Hanmi Rubber&Plastics, Korea), poly(tetrauoroethylene) (Hanmi Rubber&Plastics, Korea), and poly(ethylene) (CS Hyde
Company, IL, U.S.A.) were ultrasonically cleaned in ethanol before use. PDMS elastomer was prepared by mixing a precursor and a curing agent, at a 10:1 (wt/wt)
ratio, and was cured at 60  C for 12 h. For the poly(dopamine) coating, the substrates

were immersed into a dopamine solution (2 mg/ml in 10 mM Tris, pH 8.5) at 25  C.

The coating process was carried out for 16 h, unless a different coating time was
mentioned. The coated substrates were washed with deionized water and dried
with nitrogen gas. The poly(dopamine) coating was characterized by Raman spectroscopy and contact angle measurement. Raman spectra were obtained by accumulating 20 scans with a resolution of 2 cm1 in the range of 10002000 cm1 by
LabRAM HR UV/Vis/NIR (Horiba Jobin Yvon, France). The contact angle was determined by contact angle analyzer (Surface Electro Optics Co., Korea).
2.2. Cell culture
Mouse osteoblast MC3T3-E1 (subclone 4) was maintained in a-MEM (Welgene,
Korea) with 10% FBS (Welgene, Korea) and 1% antibiotics (Invitrogen, CA, U.S.A.); rat
pheochromocytoma PC12 was maintained in MEM (Welgene, Korea) with 10% FBS
and 1% antibiotics. Cells were subcultured at least twice a week and were maintained at a humidied atmosphere of 95% air and 5% CO2. The uncoated and poly(dopamine)-coated substrates were sterilized, using 70% ethanol, before cell
seeding and were placed in a 24-well plate. Cells were plated at a specied cell
density and were incubated for 48 h.
2.3. Cell morphology/cytoskeleton observation
The morphology of cells grown on the uncoated or poly(dopamine)-coated
substrates was observed by cytoplasm staining, using calcein AM (L3224, Invitrogen,
CA, U.S.A.), and by actin lament staining, using rhodaminephalloidin (Invitrogen,

Fig. 1. (a) Schematic illustration of cell adhesion on substrates modied by mussel-inspired poly(dopamine). (b) Raman spectra and (c) contact angle analysis of poly(dopamine)coated substrates. For the contact angle measurement, the substrates were coated with poly(dopamine) for 24 h. The Raman peaks at 1350/1600 cm1 and converging contact
angles (to approximately 60 ) indicate the formation of poly(dopamine) ad-layer on various material surfaces.

S.H. Ku et al. / Biomaterials 31 (2010) 25352541

2537

Fig. 2. Poly(dopamine) layers signicantly promoted cell adhesion on a variety of non-wetting substrates. (a) Analysis of cell morphology, (b) quantication of total projected area,
(c) quantication of projected area per cell, (d) cytoskeleton organization, and (e) fold increase of cell viability for MC3T3-E1 grown on unmodied or poly(dopamine)-modied
substrates. MC3T3-E1 cells adhered well and proliferated on non-wetting substrates when the substrates were modied with poly(dopamine). The scale bar represents 100 mm.

2538

S.H. Ku et al. / Biomaterials 31 (2010) 25352541

CA, U.S.A.). The cell density was as follows: 1  104 cells/well for MC3T3-E1 and
4  104 cells/well for PC12. After 48 h, cells were stained with calcein AM and were
observed by laser scanning confocal microscope (LSM510, Carl Zeiss, Germany). The
images were analyzed by Image J software (freely available at the following address:
http://rsb.info.nih.gov/ij/). To investigate cytoskeleton organization, MC3T3-E1 cells
were xed with 3.7% formaldehyde for 10 min, permeabilized with 0.1% Trion X-100
for 5 min, and stained with Rhodaminephalloidin for 20 min in the dark. The actin
laments were observed by laser scanning confocal microscope.
2.4. Cell viability
The viability of cells grown on the uncoated or poly(dopamine)-coated
substrates was analyzed by MTT assay. The cell density for MTT assay was adjusted to
2  104 cells/well for MC3T3-E1 and to 4  104 cells/well for PC12. After the addition
of 100 ml of MTT solution (5 mg/ml in PBS, pH 7.4; Sigma, MO, U.S.A.) to each well, the
plate was incubated at 37  C for 3 h. After removing media, the resulting purple
formazan was dissolved in 400 ml of dimethylsulfoxide, and the absorbance at
595 nm was measured by a Victor3 microplate reader (PerkinElmer Inc., MA, U.S.A.).
2.5. Protein adsorption
To analyze protein adsorption, the uncoated and poly(dopamine)-coated PTFE
were incubated in a serum-containing solution at room temperature for 1 h.
Adsorbed proteins were analyzed by X-ray Photoelectron Spectroscopy (ESCA2000,
Thermo VG Scientic, UK). XPS analysis was conducted with an Mg Ka line as an Xray source at ultrahigh vacuum (109 torr). The spectra were taken at a pass energy
of 0.1 eV.
2.6. Surface energy measurement
The critical surface tensions (gc0 ) of unmodied and poly(dopamine)-modied
PTFE were measured by examining different surface tensions (glv) of various liquids
with the Zisman method. The liquids included water (72.8 dynes/cm), glycerol
(64 dynes/cm), ethylene glycol (47.7 dynes/cm), and pyridine (38 dynes/cm). The
critical surface tension value is the zero contact angle obtained by the extrapolation
of the plot of liquid surface tension versus contact angle.

3. Results and discussion

We developed a general route for enhancing cell adhesion and
viability on anti-fouling surfaces. As illustrated in Fig. 1a, we
supposed that the mussel-inspired poly(dopamine) can be a useful
ad-layer that primes surfaces for cell attachment on versatile
biomaterials to which the existing methods cannot be applied. For
the proof-of-concept, we prepared biomaterial substrates that are
known to be highly resistant to cell adhesion. The substrates
include poly(ethylene) (PE), poly(tetrauoroethylene) (PTFE), silicone rubber, and poly(dimethyl-siloxane) (PDMS). In addition,

a glass substrate, which has been widely used for mammalian cell
culture, was used as a control to demonstrate the material versatility of our approach. The aforementioned substrates were modied with mussel-inspired poly(dopamine) by immersing the
substrates into an aqueous dopamine solution (2 mg/ml in 10 mM
Tris buffer, pH 8.5) for 16 h. The poly(dopamine) lms were characterized by Raman spectroscopy (Fig. 1b). New broad peaks
commonly appeared at approximately 1350 cm1 (stretching of
catechol) and 1600 cm1 (deformation of catechol) after the poly(dopamine) coating in addition to intrinsic substrate peaks [23].
The change of static contact angles after coating (76.9 / 65.0 for
PE; 108.5 / 58.7 for PTFE; 104.2 / 68.6 for silicone rubber;
104.5 / 65.5 for PDMS; 19.3 / 50.0 for glass) provided
evidence of poly(dopamine) functionalization on all tested materials (Fig. 1c).
The facilitation of cell adhesion on the poly(dopamine) ad-layer
was investigated by culturing mouse osteoblast MC3T3-E1 cells
and staining them with calcein AM. When the osteoblasts were
seeded onto non-adhesive PE, PTFE, silicone rubber, and PDMS
substrates, the cells barely adhered and spread (Fig. 2a, left
column), whereas the cells cultured on poly(dopamine)-modied
substrates exhibited normal adhesion (Fig. 2a, right column). The
total area of cell adhesion was quantied, as shown in Fig. 2b; the
total projected area increased remarkablyabout 14-fold, on an
average. In the case of silicone rubber, for example, the total area
changed from 2300 mm2 to 61,600 mm2 (a 26.8-fold increase) after
the poly(dopamine) coating. The results indicate that poly(dopamine) can greatly enhance cell adhesion on various non-wetting
substrates. In contrast, there was only a negligible difference
between unmodied and poly(dopamine)-modied glass
substrates because glass itself allowed good adhesion of cells before
the modication.
We found that the cells on poly(dopamine) layers were biologically adhered, not physically adsorbed, by undergoing general cell
adhesion processes of 1) substrate attachment, 2) spreading, and 3)
cytoskeleton development [24]. We quantitatively evaluated the
projected area per cell (Fig. 2c), which can measure an individual
cells spread. According to our analysis, the projected areas were
approximately 600 mm2 per cell when cells were grown on
unmodied non-wetting substrates, but the projected areas of cells
cultured on poly(dopamine)-modied substrates signicantly
increased, up to 16002000 mm2 per cell. In addition to the

Fig. 3. (a) Cell morphology and (b) fold increase of cell viability for PC12 grown on uncoated or poly(dopamine)-coated substrates. On poly(dopamine)-coated substrates, PC12 cells
exhibited high viability. The scale bar represents 100 mm.

S.H. Ku et al. / Biomaterials 31 (2010) 25352541

enhanced cell spreading on poly(dopamine)-modied substrates,

an accelerated development of cell cytoskeleton was also observed
when we stained actin laments (Fig. 2d). Cells that had adhered on
poly(dopamine)-modied PTFE exhibited well-stretched actin
bundles similar to those shown in cells that had adhered on normal
glass substrate, indicating that cells on poly(dopamine) ad-layers
underwent the aforementioned general adhesion processes (i.e.,
substrate attachment / spreading / cytoskeleton development).
Our results from cell viability test provided an additional evidence
for enhanced cell adhesion on poly(dopamine)-modied substrates
(Fig. 2e). When cells were cultured on the modied substrates, cell
viability increased, ranging from two-fold (for PE and PTFE) to vefold (for silicon rubber). In the case of a glass substrate, cell viability
was not affected by the surface modication, indicating that a poly(dopamine) layer itself is not toxic to cells. The enhancement of
cell adhesion by a poly(dopamine) layer was further conrmed by
using a different cell line, rat pheochromocytoma PC12. PC12 cells
did not show any noticeable change in their morphology, but there

2539

was a signicant increase in the number of attached cells, which

demonstrated the enhancement of cell adhesion on poly(dopamine) layer (Fig. 3a). The cell viability of PC12 was even much
more enhanced than that of MC3T3-E1 cells; 11.3-fold for silicone
rubber, 10.2-fold for PDMS, and 3.2-fold for PTFE (Fig. 3b). All the
results from our observation on the cell morphology and viability of
MC3T3-E1 and PC12 cells indicate that the mussel-inspired poly(dopamine)-coating is non-toxic to cells and that non-wetting
substrates, which are strongly resistant to cell adhesion, can be
easily converted to bioactive materials.
Many surface modication strategies had been reported previously for the improvement of cell adhesion on articial scaffolds
[2527]. Most commonly used coating materials include ECM
components (e.g., collagen) and polycations (e.g., poly-lysine).
According to a previous report [28], however, the adsorption of
collagen was not sufcient to increase the cell adhesion on PDMS
substrate to the similar level on tissue culture plastic and covalent
bonding of collagen to the substrate was needed through complex

Fig. 4. (ac) XPS C(1s) core level high resolution spectra of (a) poly(dopamine)-modied PTFE before serum-treatment, (b) serum-exposed PTFE surfaces modied by poly(dopamine),
and (c) serum-treated unmodied PTFE. The adsorption of serum proteins, indicated by the increase of C]O peak at 288.5 eV, occurred on both uncoated and poly(dopamine)-coated
surfaces. (d) Measurement of critical surface tension (gc) for unmodied and poly(dopamine)-modied PTFE. (e) Proposed mechanism of serum protein-mediated cell adhesion on
poly(dopamine) layer.

2540

S.H. Ku et al. / Biomaterials 31 (2010) 25352541

immobilization steps to promote the cell adhesion. In contrast,

poly(dopamine) ad-layer itself can act as a strong anchor between
cells and substrates without any covalently grafting [2]. In case of
poly-D-lysine, the enhancement of cell adhesion was dependent on
the type of substrates and cell lines [29], but our strategy using
poly(dopamine) ad-layer could increase the cell adhesion efciency
on different types of substrates and cell lines.
In order to investigate possible reasons for the enhancement of
cell adhesion by the poly(dopamine) coating, we analyzed surfaces
of unmodied and poly(dopamine)-modied PTFE substrates for
the adsorption of serum proteins. The substrates were incubated in
a serum protein solution (a-MEM containing 10% FBS) for 2 h and
were then extensively rinsed with deionized water. Our analysis
through X-ray photoelectron spectroscopy (XPS) showed that when
poly(dopamine)-modied PTFE was incubated in a serumcontaining solution, the intensity of the amide carbonyl peak
(NHC]O), appearing at w288.5 eV, was increased (Fig. 4b),
compared to that of the modied PTFE without the incubation
(Fig. 4a). Likewise, the same amide carbonyl peak with a similar
intensity was also detected in the unmodied PTFE substrate that
was exposed to a serum protein solution (Fig. 4c), indicating that
protein adsorption occurs irrespective of the poly(dopamine)
coating. According to our observations, a dramatic difference in cell
adhesion was caused by coating the substrate with poly(dopamine), as shown in Figs. 2 and 3, although serum proteins were
adsorbed to both unmodied and poly(dopamine)-modied
substrates (Fig. 4b, c). We attribute the discordance to a possible
denaturation of proteins adsorbed onto non-wetting surfaces. Since
the surface energy signicantly inuences protein conformation
and cell adhesion [30,31], we analyzed critical surface tensions (gc0 )
for unmodied and poly(dopamine)-modied PTFE substrates by
using the Zisman method. According to our results (Fig. 4d), the
critical surface tension (15.9 dynes/cm) for the unmodied PTFE
increased up to 39.2 dynes/cm after the poly(dopamine) modication. The critical surface tension of poly(dopamine) falls into
a suitable range for cell adhesion (3540 dynes/cm) [31]. Nonwetting substrates that have low surface energies have been
reported to result in protein denaturation, exposing the inner
hydrophobic residues of proteins and preventing specic interactions between the adsorbed proteins and cells [32,33]. According to
a previous study, the catalytic activity of immobilized enzymes on
poly(dopamine) layers was fully retained, indicating that no alteration in protein structure was caused by the poly(dopamine) [34].
Thus, we suggest that poly(dopamine) can be a versatile surface
modier that can minimize the denaturation of serum proteins by
adjusting the surface energy of materials, resulting in better cell
adhesion, as illustratively depicted in Fig. 4e. A detailed mechanism
underlying the specic interaction between cell and poly(dopamine)-coated material remains to be investigated in further
studies.
4. Conclusions
We demonstrated a general route for promoting cell adhesion
on non-wetting surfaces that are highly adhesion-resistant.
According to our results, the mussel-inspired poly(dopamine)
modication can be applied to virtually any type of substrates
without any toxic effect to cells. Cells underwent normal adhesion
processes on the poly(dopamine) ad-layer, which was conrmed by
cell morphology, cytoskeleton development, and cell viability
examinations. We envision that the bio-inspired poly(dopamine)
coating can be a powerful route for converting a variety of nonbioactive substrates into bioactive ones. Thus, this approach will be
invaluable in biomedical applications that require precise control of
cellmaterial interactions.

Acknowledgements
This study was supported by the National Research Foundation
(NRF) via National Research Laboratory (NRL) (R0A-2008-00020041-0), Converging Research Center (2009-0082276), and World
Class University (R31-2008-000-10071-0) Programs. This research
was also partially supported by the BioGreen 21 Program
(20070301034038), Republic of Korea.
Appendix
Figures with essential colour discrimination. Most of the gures
in this article may be difcult to interpret in black and white. The
full colour images can be found in the online version, at doi:10.
1016/j.biomaterials.2009.12.020.
References
[1] Waite JH. Adhesion a la moule. Integr Comp Biol 2002;42:117280.
[2] Lee H, Dellatore SM, Miller WM, Messersmith PB. Mussel-inspired surface
chemistry for multifunctional coatings. Science 2007;318:42630.
[3] Waite JH, Qin X. Polyphosphoprotein from the adhesive pads of Mytilus edulis.
Biochemistry 2001;40:288793.
[4] Lee H, Scherer NF, Messersmith PB. Single-molecule mechanics of mussel
adhesion. Proc Natl Acad Sci USA 2006;103:129993003.
[5] Wozniak MA, Modzelewska K, Kwong L, Keely PJ. Focal adhesion regulation of
cell behavior. Biochim Biophys Acta 2004;1692:10319.
[6] Bettinger CJ, Langer R, Borenstein JT. Engineering substrate topography at the
micro- and nanoscale to control cell function. Angew Chem Int Ed 2009;48:
540615.
[7] Chen H, Yuan L, Song W, Wu Z, Li D. Biocompatible polymer materials: role of
protein-surface interactions. Prog Polym Sci 2008;33:105987.
[8] Stevens MM, George JH. Exploring and engineering the cell surface interface.
Science 2005;310:11358.
[9] Harbers GM, Emoto K, Greef C, Metzger SW, Woodward HN, Mascali JJ, et al.
Functionalized poly(ethylene glycol)-based bioassay surface chemistry that
facilitates bio-immobilization and inhibits nonspecic protein, bacterial, and
mammalian cell adhesion. Chem Mater 2007;19:440514.
[10] Zhang Z, Zhang M, Chen S, Horbett TA, Ratner BD, Jiang S. Blood compatibility
of surfaces with superlow protein adsorption. Biomaterials 2008;29:428591.
[11] Wischerhoff E, Uhlig K, Lankenau A, Borner HG, Laschewsky A, Duschl C, et al.
Controlled cell adhesion on PEG-based switchable surfaces. Angew Chem Int
Ed 2008;47:56668.
[12] Khoo X, Hamilton P, OToole GA, Snyder BD, Kenan DJ, Grinstaff MW. Directed
assembly of PEGylated-peptide coatings for infection-resistant titanium metal.
J Am Chem Soc 2009;131:109927.
[13] Zhu Y, Chian KS, Chan-Park MB, Mhaisalkar PS, Ratner BD. Protein bonding on
biodegradable poly(L-lactide-co-carprolactone) membrane for esophageal
tissue engineering. Biomaterials 2006;27:6878.
[14] Dennes TJ, Hunt GC, Schwarzbauer JE, Schwartz J. High-yield activation of
scaffold polymer surfaces to attach cell adhesion molecules. J Am Chem Soc
2007;129:937.
[15] Ohmuro-Matsuyama Y, Tatsu Y. Photocontrolled cell adhesion on a surface
functionalized with a caged arginine-glycine-aspartate peptide. Angew Chem
Int Ed 2008;47:75279.
[16] Panitch A, Yamaoka T, Fournier MJ, Mason TL, Tirrell DA. Design and biosynthesis of elastin-like articial extracellular matrix proteins containing periodically spaced bronectin CS5 domains. Macromolecules 1999;32:17013.
[17] Dee KC, Andersen TT, Bizios R. Design and function of novel osteoblastadhesive peptides for chemical modication of biomaterials. J Biomed Mater
Res 1998;40:3717.
[18] Shin H, Jo S, Mikos AG. Biomimetic materials for tissue engineering. Biomaterials 2003;24:435364.
[19] Jiang T, Abdel-Fattah WI, Laurencin CT. In vitro evaluation of chitosan/poly(lactic acid-glycolic acid) sintered microsphere scaffolds for bone tissue engineering. Biomaterials 2006;27:4894903.
[20] Wang J, de Boer J, de Groot K. Proliferation and differentiation of osteoblastlike MC3T3-E1 cells on biomimetically and electrolytically deposited calcium
phosphate coatings. J Biomed Mater Res 2009;90A:66470.
[21] Guo Y, Li M, Mylonakis A, Han J, MacDiarmid AG, Chen X, et al. Electroactive
oligoaniline-containing self-assembled monolayers for tissue engineering
applications. Biomacromolecules 2007;8:302534.
[22] Bettinger CJ, Bruggeman JP, Misra A, Borenstein JT, Langer R. Biocompatibility
of biodegradable semiconducting melanin lms for nerve tissue engineering.
Biomaterials 2009;30:30507.
[23] Fei B, Qian B, Yang Z, Wang R, Liu WC, Mak CL, et al. Coating carbon nanotubes
by spontaneous oxidative polymerization of dopamine. Carbon 2008;46:
1792828.
[24] Anselme K. Osteoblast adhesion on biomaterials. Biomaterials 2000;21:66781.

S.H. Ku et al. / Biomaterials 31 (2010) 25352541

[25] Yoo HS, Kim TG, Park TG. Surface-functionalized electrospun nanobers for
tissue engineering and drug delivery. Adv Drug Deliv Rev 2009;61:103342.
[26] Martins A, Pinho ED, Faria S, Pashkuleva I, Marques AP, Reis RL, et al. Surface
modication of electrospun polycaprolactone nanober meshes by plasma
treatment to enhance biological performance. Small 2009;5:1195206.
[27] Ma Z, Gau C, Gong Y, Shen. Cartilage tissue engineering PLLA scaffold with
surface immobilized collagen and basic broblast growth factor. Biomaterials
2005;26:12539.
[28] Wipff P-J, Majd H, Acharya C, Buscemi L, Meister J-J, Hinz B. The covalent
attachment of adhesion molecules to silicone membranes for cell stretching
applications. Biomaterials 2009;30:17819.
[29] Sen A, Barizuddin S, Hossain M, Polo-Parada L, Gillis KD, Gangopadhyay S.
Preferential cell attachment to nitrogen-doped diamond-like carbon (DLC:

[30]
[31]
[32]

[33]
[34]

2541

N) for the measurement of quantal exocytosis. Biomaterials 2009;30:

160412.
Baier RE. Surface behaviour of biomaterials: the theta surface for biocompatibility. J Mater Sci Mater Med 2006;17:105762.
Ozcan C, Hasirci N. Plasma modication of PMMA lms: surface free energy
and cell-attachment studies. J Biomater Sci Polym Ed 2007;18:75973.
Grinnel F, Feld MK. Fibronectin adsorption on hydrophilic and hydrophobic
surfaces detected by antibody binding and analyzed during cell adhesion in
serum-containing medium. J Biol Chem 1982;57:488893.
Lu DR, Park K. Effect of surface hydrophobicity on the conformational changes
of adsorbed brinogen. J Colloid Interface Sci 1991;144:27191.
Lee H, Rho J, Messersmith PB. Facile conjugation of biomolecules onto surfaces
via mussel adhesive protein inspired coatings. Adv Mater 2009;21:4314.