Cellular Functionality on Nanotubes of Ti-30Ta Alloy

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15 Νοε 2013 (πριν από 4 χρόνια και 1 μήνα)

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Cellular Functionality on Nanotubes of Ti
-
30Ta Alloy

Patricia

Capellato
1
,
*
,
+
, Barbara S. Smith
2
,
+
, Ketul C. Popat
2
,3,
#
,
Ana P. R. Alves Claro
1
,#


1
Department of Materials, Faculty of Engineering Guaratinguetá, Sao Paulo State University
-

UNESP
, Av. Ariber
to Pereira da Cunha,
333, Pedregulho, CEP 12516
-
410, Guaratinguetá
, SP,
Brazil
.

2

School of Biomedical Engineering, Colorado State University, Fort Collins CO 80523, USA

3
Department of Mechanical Engineering, Colorado State Uni
versity, Fort Collins, CO 80
523,
USA


+
,#

Authors contributed equally to this article

*Author of correspondence:

Patricia Capellato,
Department of Materials, Faculty of Engineering
Guaratinguetá, Sao Paulo State University
-

UNESP, Av.
Ariberto Pereira da Cunha,

333,
Pedregulho, CEP
12516
-
410, Guaratinguetá, SP, Brazil

E
-
mail:
pat_capellato@yahoo.com.br



Abstract

Cellular Functionality on
n
anotubes of Ti
-
30Ta Alloy

is the subject of this research
.

Recent
studies have identified
strong
correlations between anodized metals
and

the production of highly
biomimetic nanoscale topographies
.
These surfaces provide an interface
of

enhanced

biocompatibility

that exhibits a high degree of oxidation and surface energy.

In this study, the
mechanical

substrate

and topographical
surface properties

on nanotubes of Ti
-
30Ta alloy
were

investigated using
scanning electron microscopy (SEM),
energy
-
dispersive spectroscopy (EDS)
and
contact angle
measurement. The

anodization process was performed
in an
electr
olyte
solution contain
ing

HF (48%) and H
2
SO
4
(98%) in the volumetric ratios 1:9 with

the

addition of
5% dimethyl sulfoxide (DMSO)

at 35V for 40 min
. Human dermal fibroblasts (HDF, neonatal)
were utilized to evaluate the b
iocompatibility

of Ti
-
30Ta nanotube
s after 1 and 3 days of culture
.

The

results
presented
identify altered
material

properties and improved cellular interaction on
Ti
-
30Ta nanotubes

as compared to the control substrates.


Key Words:

Ti
-
30Ta
nanotube arrays
;

Human dermal fibroblasts
.




1. I
ntroduction

In order to facilitate the long
-
term success of implantable devices, both the substrate

[
19
]

and the surface

[
20
]

must be considered. The ideal implantable biomaterial should embody
mechanical properties similar to that of the natural tissue with which it will be interacting

[
21
]
.
Clinical application
s currently utilize materials such as titanium (Ti) and titanium alloys, steel,
cobalt alloys, and tantalum (Ta)

[
19
,
27
,
28
]

[
29
]
. New
developments

in material science have
motivated alloy
-
directed research, showing a high correlation between improved mechanical
properties and alloyed titanium substrates wit
h various

non
-

allergic and non
-
toxic
metals, such
as Ta, Zr, Nb, Hf, Mo, and Sn

[
13
,
19
,
29
-
42
]
.

Of the alloys

tested
, 30% Ta with Ti exhibits

lower elastic modulus,

improved strain
-
resistance and elongation to failure,
and
favorable
biocompatibility

[
29
-
33
,
40
,
47
]
.

Current approaches used to modify material interfaces utiliz
e

novel techniques such as
annodization

[
49
,
50
]
, alkaline and heat treatment
s

[
34
,
35
]
,
ion
implantation

[
51
,
52
]
,
electrochemical etching

[
45
,
53
]
,
simulated body fluid (SFB)

[
25
,
54
]


and
plasma spray coatings

[
38
,
55
]
.

These surfaces have been shown to provide an
interface
that
exhibits

a higher degree of

oxidation

and

surface energy

[
61
]
, as well as

improved
biocompatibility
.

Previous studies have
shown
the

evi
dence supporting the use of anodized titanium for
implantable devices that interact with both hard and soft tissue

[
49
,
50
,
55
,
56
,
58
,
59
]
.
I
n this

the
sur
face
topographical
properties

of Ti
-
30Ta nanotubes
were investigated
using

scanning
electron microscopy (SEM),
energy
-
dispersive spectroscopy (
EDS
)
,
and
c
ontact angle

measurement
[
62
]
.

The b
iocompatibility
was

evaluated
using human dermal fibroblasts (HDF,
neonatal)
.

The

cell
adhesion, proliferation,
viability
,

cytoskeleton

organization, and morphology
were
investigated using fluorescence microscope imaging,
biochemical

assay and SEM imaging

respectively
.
The

results
presented
identify altered mechanical properties, and improved cellular
interaction on Ti
-
30Ta

nanotube as compared to the control substrates.


2
.
M
ethods and Materials

2.
1

Anodization

of Ti
-
30Ta
A
lloy


The anodization process was performed using platinum as the counter electrode and the
Ti
-
30Ta alloy substrate as the working electrode connected to

a power supply (Fisher Scientific
FB300 Electrophoresis)
.
The electrolyte solution contained HF concentrate (48%) and H
2
SO
4
(98%) in the volumetric ratios 1:9 with

the

addition of 5% dimethyl sulfoxide (DMSO)

[
49
]
. The
experiment was performed at room temperature.

In addition, the annealing of the
Ti
-
30Ta
nanotube

was

performed in an
oxygen ambient
furnace
at 530ºC
, with a ramping
rate of 1º C/min
for 3 hrs.
Following annealin
g, all substrates

were
stored

in

a

dissector until
further
characterization.
The

surface

topography of the anodized s
ubstrates

was characterized by SEM

imaging (JEOL JSM 6100)
.


In order to obtain cross
-
sectional images, the surface
was
mechanically scratch
ed
with metallic tool and imaged
by tilting the chamber to

70°
.

The
elemental surface composition

was
determined

using

EDS

(JOEL
JSM 6100).

The

hydrophilicity

of the substrate surfaces

was investigated by a sessile drop method (2 ml) using a
contact angle

goniometer (Kruss DSA 10) equipped with video capture.


2.
2

Cell Culture


Human Dermal Fibroblast (HDF, Clonetics) cells, isolated from neonatal
. The cell
density was determined by trypan blue dye exclusion, using a hemocytometer. The experiments
for
this study were performed using
fourth

passage HDF cells.


HDF cells were seeded on
polished Ti30Ta
(control) and

anodized

Ti30Ta

alloys
(substrate

diameter:
3.0 mm)

in a 24
-
well plate.
The substrates
stained for DAPI were
concurrently stained F
-
actin to e
valuate their cytoskeletal organization using
f
luorescence
microscope imaging. The substrates were incubated in rhodamine
-
conjugated phalloidin
(dilution 1:40) for 20 min at room temperature to stain for F
-
actin on the cell membranes. The
substrates were

imaged with a fluorescence microscope using DAPI BP 445/50 blue filter

and

HQ Texas Red BP 560/40 red filter (Zeiss). The cell morphology was investigated using SEM
imaging to visualize the cellular interaction with the nanotube architecture
, after 1 and

3 days of
culture
.

Each experiment was reconfirmed on at least three different substrates from (
n
min
=
3
).
A
ll the quantitative results were analyzed using an analysis of variance (ANOVA). Statistical
significance was considered at p < 0.05. During th
e analysis, variances among each group were
not assumed to be equal and
a

two
-
sample

t
-
test approach was used to test the significance
b
etween the Ti
-
30Ta alloys and the Ti
-
30Ta nanotube
. This analysis was conducted using the
Microsoft Office Excel

data a
nalysis software
.


3. Results and Discussion

The anodized surface has been shown enhanced osseointegration in Ti cp, Ti
-
binary and
Ti
-
ternary alloys
[
16
,
20
,
50
,
60
,
65
]
.
Thus,
in this study
Ti
-
30Ta substrate
s with a vertically
oriented array of nanotubes have been evaluated to determine their effect on HDF cells.
Fibroblast cells

proliferate rapidly

in vivo
, producing a highly dense matrix of proteins and
growth factors through an organized
network of cells
with elongated morpholog
ies

[
59
]
.

In this

study, the functionality of fibroblast cells has been investigated after 1 and 3 days of culture on
Ti
-
30Ta
nanotube

as compared to the control subst
rates
.

The surface charge of a biomaterial is among the most important properties in an
implantable device. This trait translates into the hydrophilicity or relative wettability of a
material, and plays a key role in directing cell
-
material interaction.
In biomedical application
s,

lower hydrophilic
ity or increased hydrophobicity

is required for
improved

cellular interaction.
Previous studies have related the

surface energy

of a biomaterial with cellular functionality such
as

protein adsorption
,

platelet a
dhesion and activation

leading to

blood coagulation, and bacterial
adhesion
[
52
,
64
,
76
]
.

Thus, in this study, the

hydrophilic behavior of
anodized and unaltered

Ti
-
30Ta
substrates

was investigated

by measuring their respective contact angles
.

The cell cytoskeleton is a structural masterpiece, composed of a ne
twork of
microfilaments, microtubules and intermediate filaments; whose organization is indicative of
intra
-

and extra
-
cellular communication, integration, recruitment and differentiation. Cellular
health, reproduction, tissue mechanics and cell/tissue fu
nctionality are all dependent on the
ability of the cell cytoskeleton to reorganize itself. Thus, the substrates
stained for DAPI were
concurrently stained F
-
actin to evaluate their cytoskeletal organization using
f
luorescence
microscope imaging
, after 1
and 3 days of culture
.

The fluorescence images confirmed the
presence of cytoskeletal elongation

on both substrates; once again identifying the Ti
-
30Ta alloy
as promoting positive cellular proliferation, communication and integration. However, the
defini
tive presence of spherical cells on the untreated Ti
-
30Ta substrate indicates reduced
cellular integration as compared to the nanotube Ti
-
30Ta substrates. This heightened cellular
interaction and integration seen on the nanotube surface will likely lead t
o increased protein

expression and extracellular matrix production on and around the biomaterial interface, further
improving biomaterial integration.

SEM imaging

was utilized to identify the effects of the nanotube interface with respect to
fibroblast mo
rphology after 1 and 3 days of culture
. The results indicate a considerable increase
in short
-
term fibroblast
-
nanotube interaction
.
After 3 days of culture, the unaltered Ti
-
30Ta
substrate shows a clear mixture of both activated and unactivated cells on t
he material surface;
however high
-
magnification images of the nanotube Ti
-
30Ta substrates identify extracellular
matrix production, not present on the control substrates.

Cellular interactions with their
environment direct further tissue and ECM productio
n
.

The results of the nanotube Ti
-
30Ta
substrates identify a promising material interface for improved tissue
-
biomaterial integration.


4. Conclusion



The
surface

properties of the Ti
-
30Ta
nanotube

show
improved wettability properties
as
compared to
Ti
-
30Ta alloy
.
Surface

elemental composition
analysis

confirmed
reduction in the
amount of

tantalum at the material interface. The water
-
drop method identified a contact angle
of 15.04˚ on the nanotube surface, indicating a hydrophilic interface,
which is preferable

for
eliciting a favorable environment for cellular interaction. Cellular anal
ysis identified improved
fibroblast functionality

on the nanotube surface, showing increased elongation,

and extracellular
matrix production on the Ti
-
30Ta nanotubes.
In conclusion, this is the first study on fabrication
of nanotubes on Ti
-
30Ta alloy surf
ace and evaluating cellular interaction on the nanotube
architecture.
Thus, the formation of the nanotube on Ti30Ta alloy may have poten
t
ial application
as interface for implantable devices.



5. Acknowledgements

Partial funding support for this work was
provided by Brazilian agencies CNPq via grant
Doctored sandwich, project number 201271/2010
-
9.
The authors would like to thank Patrick
McCurdy for his assistance with scanning electron microscopy.


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