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Cours Polytech Orsay Chapitre 2 Prothèse – TiO2 07/10/2010 - 1 -
BIOMATERIAUX
16 heures
Chapitre 2 L’oxyde de Titane TiO2
D. Bazin
Laboratoire de Physique des Solides UMR 2502,
Université Paris Sud, Bât 510 91405 Orsay Cedex, France.
Cours Polytech Orsay Chapitre 2 Prothèse – TiO2 07/10/2010 2
PLAN
Chapitre 0 Introduction
Chapitre 1 Sondes & Polymères
Chapitre 2 Prothèse en alliage à base de titane
Chapitre 2.1 Aspect médical Chapitre 2.1a La prothèse de Hanche
Chapitre 2.1b Les cages rigides
Chapitre 2.1c Implants dentaires
Chapitre 2.2 Métallurgie Chapitre 2.2a La raideur des alliages
Chapitre 2.2b La résistance à la fatigue
Chapitre 2.3 Surface d’une prothèse en titane
Chapitre 2.3a Nature de la surface, présence de lacunes oxygène et de groupes
hydroxyles
Chapitre 2.3b la structure de l’oxyde TiO2, analyse fine des diagrammes de diffraction
Chapitre 2.3c Taille et stabilité des particules de TiO2, déformation structurales
observées lors de la transition de phase, mécanisme de croissance et inhibition de la
transformation de phase par passivation
Chapitre 2.4 Revêtement d’apatite Chapitre 2.4a Mécanismes de formation de l’apatite (pH, taille, épaisseur),
Optimisation de la couche de TiO2 (précurseur, Température,
Chapitre 2.4b Composition chimique de l’interface Ti/HA
Chapitre 2.4e Influence de la taille des cristallites
Chapitre 2.4g Modification de la morphologie des cristaux d’apatites déposés
Chapitre 2.15 greffage à la surface de prothèse en titane
Chapitre 2.16 Traitement de surface d’une prothèse en titane
Chapitre 2.5 Etude de la surface d’un implant réel
Chapitre 2.6 Autres applications Chapitre 2.6a TiO2 comme agent anticancéreux
Chapitre 2.6b TiO2 comme agent antibactérien (Ag/TiO2)
Chapitre 2.6c TiO2 comme microfabricated medical device
Chapitre 2.7 Toxicité des nanoparticules de TiO2
Chapitre 2.7a Réponse cellulaire
Chapitre 2.7b Par inhalation
Chapitre 2.7c A travers la peau
Cours Polytech Orsay Chapitre 2 Prothèse – TiO2 07/10/2010 3
Chapitre 2.4 Revêtement d’apatite
Chapitre 2.4a Mécanismes de formation de l’apatite1
Apatite formation induced by negatively charged nanocrystalline TiO2
coatings soaked in simulated body fluid (SBF) is affecting by factors such as
- pH,
- size of TiO2 particles
- thickness of TiO2 coatings,
1. Yang et al., Mechanism and kinetics of apatite formation on nanocrystalline TiO2 coatings:
A quartz crystal microbalance study, Acta Biomaterialia 4 (2008) 560–568
Cours Polytech Orsay Chapitre 2 Prothèse – TiO2 07/10/2010 4
Two different stages were clearly observed in the process of apatite
precipitation, indicating two different kinetic processes.
At the first stage, the Ca2+
ions in SBF were initially attracted to the
negatively charged TiO2 surface,
and then the calcium titanate formed at the interface combined with
phosphate ions, consequently forming apatite nuclei.
After the nucleation, the calcium ions, phosphate ions and other
minor ions (i.e. CO2-3
and Mg2+
) in supersaturated SBF deposited spontaneously
on the original apatite coatings to form apatite precipitates.
Cours Polytech Orsay Chapitre 2 Prothèse – TiO2 07/10/2010 5
Optimisation de la couche de TiO2 (Température) 2
TiO2 thin films were prepared on NiTi surgical alloy by sol–gel method.
Tetrabutyl titanate (Ti(C4H9)4, or Ti(OBu)4, from Zhejiang, China) was used as
TiO2 precursor.
The forming process, surface morphology and structure of the films were
studied by X-ray diffraction and atomic force microscopy.
2. Liu et al., Sol–gel deposited TiO2 film on NiTi surgical alloy for biocompatibility
improvement, Thin Solid Films 429 (2003) 225–230
Cours Polytech Orsay Chapitre 2 Prothèse – TiO2 07/10/2010 6
The results showed that nm-scale TiO2 particles were embedded in the
film of 205 nm thickness. The film existed mainly in the form of anatase, and
the film was compact and smooth. The electrochemical corrosion measurement
indicated that TiO2 thin film, as a protective layer, was effective for improving
corrosion resistance of NiTi alloy. Additionally, in vitro blood compatibility of
the film and NiTi alloy was evaluated by dynamic clotting time and blood
platelets adhesion tests. The results showed that NiTi alloy coated
with TiO2 film had improved blood compatibility.
Cours Polytech Orsay Chapitre 2 Prothèse – TiO2 07/10/2010 7
Chapitre 2.10 Influence de l’épaisseur de la couche de
TiO23
To improve the implant-tissue osteointegration, much effort has gone into
the modification of the Ti surface4,5,6. Among the various attempts
which have been made to improve the osseointegration, hydroxyapatite (HA,
Ca10(PO4)6(OH)2) coatings on Ti implants have shown good fixation to the host
bone and increased bone ingrowth to the implant. The improved
biocompatibility provided by the HA coatings is due to the chemical and
biological similarity of HA to hard tissues, and its consequent direct bonding to
host bones.
Parallel with this development, titania (TiO2) coatings on Ti have been
used to improve the corrosion resistance of Ti, which otherwise restricted its
usage in load-bearing implants over a prolonged period of time.
In practice, the very thin (at most several tens of nanometers) oxide
film on the Ti surface, which is formed in an aqueous environment, plays a
decisive role in determining the biocompatibility and corrosion behaviour of the
Ti implant. Since the corrosion resistance is known to increase with the
thickness of the oxide layer, many attempts have been made to form a thick
3. H.W. Kim et al., Hydroxyapatite coating on titanium substrate with titania buffer
layer processed by sol–gel method Biomaterials 25 (2004) 2533–2538.
4. Ratner BD. New ideas in biomaterials science-a path to engineered biomaterials. J Biomed
Mater Res 1993;27:837–50.
5. Block MS, Finger IM, Fontenot MG, Kent JN. Loaded hydroxyapatite-coated and grit-
blasted titanium implants in dogs. Int J Oral Maxillofac Implants 1989;4:219–25.
6. Nanci A, Wuest JD, Peru L, Brunet P, Sharma V, Zalzal S, et al. Chemical modification of
titanium surfaces for covalent attachment of biologica l molecules. J Biomed Mater Res
1998;40:324–35.
Cours Polytech Orsay Chapitre 2 Prothèse – TiO2 07/10/2010 8
TiO2 layer on the Ti substrate using various methods, such as anodization,
thermal oxidation, and the sol–gel process.
Fig. 1 shows the XRD patterns of the HA layer deposited on a Ti substrate
after heat treatment at various temperatures for 1 h. Prior to HA coating, the
TiO2 was pre-coated onto the Ti substrate at 500°C f or 1 h. When the HA was
heat-treated at 400°C, small apatite peaks began to appear (Fig. 1(A)). When the
heat treatment temperature was increased to 450°C and 500°C (Figs. 1(B) and
(C), respectively), the apatite peak intensities increased, indicating that there
was an improvement in crystallization.
Only the HA, TiO2, and Ti peaks were detected, regardless of
the heat treatment temperature, suggesting the absence of any
chemical reaction between the different components.
Cours Polytech Orsay Chapitre 2 Prothèse – TiO2 07/10/2010 9
SEM morphologies of the HA/ TiO2 double layer coating on the Ti substrate.
SEM images ofthe various coating systems deposited onto Ti: (A) TiO2 coating
surface; (B) HA/TiO2 double layer coating surface; and (C) HA/TiO2 double
layer coating cross sectional views. The heat treatment for each coating was
performed at 500°C for 1 h in air.
The thicknesses of the HA and TiO2 layers were approximately 200 and
200 nm, respectively. Each layer bonded firmly and had a uniform thickness
throughout on the Ti surface. Moreover, there were no delaminations or cracks
at either of the interfaces, suggesting that the bonding capability of both the
HA/TiO2 and TiO2/Ti interfaces was quite good.
Cours Polytech Orsay Chapitre 2 Prothèse – TiO2 07/10/2010 10
Le SEM ne permet pas de mettre en évidence des différences lorsque l’on
procède à des cultures cellulaires. The cellular response to the HA/TiO2 double
layer coating system was assessed by an in vitro culture method using osteoblast
cells. - (A) The cells spread and grew in intimate contact with the bare Ti surface.
- (B) On the Ti substrate coated with TiO2, the cells grew in a similar fashion to those
on the bare Ti.
(C) Also on the HA/TiO2 double-layer coated sample, the cells grew in a similar
fashion, but a little more actively compared to those on the bare Ti and TiO2 coated Ti.
Cours Polytech Orsay Chapitre 2 Prothèse – TiO2 07/10/2010 11
The cellular response to the specimen was assessed in terms of the cell
proliferation and the cell differentiation by measuring the alkaline Phosphatase
(ALP) activity.
Fig. 5. Proliferation number and ALP activity of osteoblate cells cultured on
each sample for periods of 5 and 10 days, respectively. The heat treatment for
each coating was performed at 500°C for 1 h in air.
The cell proliferation number and ALP level on the bare Ti substrate were
larger than those on the plastic control. Moreover, the cells on the coated
samples (both TiO2 coated- and HA/TiO2 double layer coated-Ti) proliferated
more and expressed higher ALP levels compared to those on the bare Ti
substrate. There was little difference between the TiO2 coated- and the HA/TiO2
double layer coated-Ti samples in terms of proliferation. However, the ALP
expression level of the cells on the HA/TiO2 double-layer coated Ti substrate
was higher than that on the TiO2 coated Ti substrate.
Cours Polytech Orsay Chapitre 2 Prothèse – TiO2 07/10/2010 12
Chapitre 2.4b Composition chimique de l’interface Ti/HA7
The sol gel technique employed in this work is based on hydrolysis and
condensation of metal alkoxides such Ti(OR) where R is an organic ligand.
The XRD technique was used to follow the crystallisation of the
produced compounds : TiO2, CaTiO3 and HA.TiO2 was crystallized in
the single phase of anatase at T= 550°C whereas rutile was the
predominant phase at T=750°C.
7. Kaciulis et al., Surface analysis of biocompatible coatings on titanium, J. of electron
Spectroscopy 95 (1998)61-69.
Cours Polytech Orsay Chapitre 2 Prothèse – TiO2 07/10/2010 13
The best quality (homogeneity and stoichiometry) of HA
coating was achieved when the substrate was first coated with
an intermediate layer of CaTiO3.
Cours Polytech Orsay Chapitre 2 Prothèse – TiO2 07/10/2010 14
Chapitre 2.12 taille des cristallites et porosité8
Titanium (Ti) and some of its alloys have been extensively applied as
orthopaedic implant materials under load-bearing conditions due to their
outstanding mechanical properties and biocompatibility9,10
.
However, the mismatch of Young’s modulus between Ti and its
alloys (90–110 GPa) and bones (0.3–30 GPa) causes severe ‘‘stress shielding”,
leading to bone resorption11
.
One way to solve this problem is to reduce the Young’s modulus of Ti-
based biomaterials by introducing a porous structure, thereby minimizing
or eliminating the stress-shielding to the tissues adjacent to the implant materials
and eventually prolonging the implant lifetime12
.
8. Xiao-Bo Chen, The importance of particle size in porous titanium and nonporous
counterparts for surface energy and its impact on apatite formation Acta Biomaterialia 5
(2009) 2290–2302
9. Brunette DM, Tengvall P, Textor M, Thomsen P. Titanium in medicine. Heidelberg:
Springer-Verlag; 2001.
10. Long M, Rack HJ. Titanium alloys in total joint replacement—a materials science
perspective. Biomaterials 1998;19:1621–39.
11. Uhthoff HK, Finneagan M. The effects of metal plates on posttraumatic remodelling and
bone mass. J Bone Joint Surg Br 1983;65:66–71.
12. Gibson LJ, Ashby MF. Cellular solid: structure and properties. Cambridge: Cambridge
University Press; 1997.
Cours Polytech Orsay Chapitre 2 Prothèse – TiO2 07/10/2010 15
13
A porous structure encourages osteointegration and prevents
implantation failure by providing spaces for bone cells, vascular and bone tissue
in growth to form mechanical interlocking14
. It has been proposed that the
optimal pore size for the cell attachment, differentiation and ingrowth of
osteoblasts and vascularization is approximately 200–500 µm15.
Using a special powder metallurgy technique, Wen et al.16
,17
successfully
fabricated a porous Ti with a porosity of 72% and a low Young’s
modulus (5.3 GPa) that exhibited a unique open-cellular porous structure.
13. http://www.covalent.co.jp/eng/rd/new_technologies/bio.html 14. Park JB, Lakes RS. Biomaterials: an introduction. New York: Plenum; 1992.
15. Clemow AJT, Weinstein AM, Klawitter JJ, Koeneman J, Anderson J. Interface mechanics
of porous titanium implants. J Biomed Mater Res 1981;15:73–82.
16. Wen CE, Mabuchi M, Yamada Y, Shimojima K, Chino Y, Asahina T. Processing of
biocompatible porous Ti and Mg. Scripta Mater 2001;45:1147–53.
17. Wen CE, Yamada Y, Shimojima K, Chino Y, Hosokawa H, Mabuchi M. Novel titanium
foam for bone tissue engineering. J Mater Res 2002;17:2633–9.
Cours Polytech Orsay Chapitre 2 Prothèse – TiO2 07/10/2010 16
Early and stable osteointegration at the interface between Ti-based
bone implant materials and a bony site is one of the most important
indicators of clinical success (new bone formation)18
. It has been reported that
excellent osteointegration can be achieved on ceramic implants through a
bioactive calcium phosphate (CaP) apatite layer formed at the bone-
implant interface19
,20
.
An apatite coating is favourable for fast bony adaptation, the absence of
fibrous tissue seams, a reduction in the healing time and an increase in the
tolerance of surgical inaccuracies21
. Moreover, apatite formation in a biological
environment also depends on the surface characteristics of
biomaterials22.
One of the most important surface properties of implants is the surface
energy, which presents the surface wettability. The wettability of an
implant material influences the degree of the contact and interaction between the
implant and the biological environment23
.
Influences of the surface energy on protein adsorption, osteoblast
adhesion, spreading and proliferation have been extensively studied24
. However,
there are still very few studies on the effect of the surface energy of metallic
substrates on bioactive apatite formation25
.
Question : Quelle est la relation entre l’énergie
de surface & taille des particules ?
18. Branemark PI, Hansson BO, Adell R, Breine U, Lindstro¨m J, Hallen O, et al.
Osseointegrated implants in the treatment of edentulous jaw. Experience from a 10-year
period. Scand J Plast Reconst Surg Hand Surg 1977;11(Suppl. 16):1–132.
19. Ohtsuki C, Kushitani H, Kokubo T, Kotani S, Yamamuro T. Apatite formation on the
surface of ceravital-type glass–ceramic in the body. J Biomed Mater Res 1991;25:1363–70.
20. Ho¨land W, Vogel W, Naumann K, Gummel J. Interface reaction between machinable
bioactive glass–ceramics and bone. J Biomed Mater Res 1985;19:303–12.
21. Kay JE. Designing to counteract the effects of initial device instability: mineral and
engineering. J Biomed Mater Res 1988;22:1127–35.
22. Chen XB, Nouri A, Li YC, Lin JG, Hodgson PD, Wen CE. Effect of surface roughness of
Ti, Zr and TiZr on apatite precipitation from simulated body fluid. Biotechnol Bioeng
2008;101:378–87.
23. Baier RE, Shafrin EG, Zisman WA. Adhesion: mechanisms that assist or impede it.
Science 1968;162:1360–8.
24. Kennedy SB, Washburn NR, Simon Jr CG, Amis EJ. Combinational screen of the effect
of surface energy on fibronectin-mediated osteoblast adhesion, spreading and proliferation.
Biomaterials 2006;27:3817–24.
25. Wang XJ, Li YC, Lin JG, Hodgson PD, Wen CE. Apatite-inducing ability of titanium
oxide layer on titanium surface: the effect of surface energy. J Mater Res 2008;23:1682–8.
Cours Polytech Orsay Chapitre 2 Prothèse – TiO2 07/10/2010 17
L’étude va porter sur différents échantillons:
Cours Polytech Orsay Chapitre 2 Prothèse – TiO2 07/10/2010 18
One of the most important surface properties of implants is the surface
energy, which presents the surface wettability. The wettability of an
implant material influences the degree of the contact and interaction between the
implant and the biological environment26
.
26. Baier RE, Shafrin EG, Zisman WA. Adhesion: mechanisms that assist or impede it.
Science 1968;162:1360–8.
Cours Polytech Orsay Chapitre 2 Prothèse – TiO2 07/10/2010 19
Chapitre 2.13 Optimisation de la couche
d’apatite27
Titanium is the most commonly used metallic material in the manufacture
of orthopedic implants, and hydroxyapatite (HA) is bioactive and biocompatible
when used as bone substitutes. To achieve better biocompatibility and excellent
mechanical performance of prostheses, coating calcium phosphates, especially
- hydroxyapatite (HA)
- silicate glass
on tough biocompatible metallic substrates has received considerable
attention28
,29
.
Li30
reported that bone-bonding strength to HA coated titanium rods was
1.0, 1.5, 2.0 and 2.5 MPa after 1, 2, 3 and 4 weeks implantation, respectively, as
determined by pull-out tests. These values were over twice that of the uncoated
titanium rods at 1–4 weeks after implantation.
Il est possible de modifier les caractéristiques structurales de la couche
d’apatite en choisissant des précurseurs différents:
The present study used dip-coating techniques to fabricate HA coating of
- organic sol–gel of Ca(NO3)2 4H2O and PO(CH3)3 ,
- inorganic sol of Ca(NO3)2 4H2O and (NH4)2 HPO4.
Scanning electron microscopy (SEM) and grazing-incidence X-ray diffraction
(XRD) have been used to characterize the morphology and the distributions of
crystallite size and micro-strains of the coatings.
27. L. Guo et al., Fabrication and characterization of thin nano-hydroxyapatite coatings on
titanium Surface & Coatings Technology 185 (2004) 268– 274.
28. D.B. Haddow, P.F. James, R. van Noort, Sol –gel derived calcium phosphate coatings for
biomedical applications, J. Sol–gel Sci. Technol. 13 (1998) 261– 265.
29. E. Saiz, M. Goldman, J.M. Gomez-Vega, A.P. Tomsia, G.W. Marshall, S.J. Marshall, In
vitro behavior of silicate glass coatings on Ti –6Al –4V, Biomaterials 23 (2002) 3749– 3756.
30. T. Li, J. Lee, T. Kobayashi, H. Aoki, Hydroxyapatite coating by dipping method, and
bone bonding strength, J. Mater. Sci. Mater. In Med. 7 (1996) 355– 357.
Cours Polytech Orsay Chapitre 2 Prothèse – TiO2 07/10/2010 20
On remarque par SEM des différences importantes de la surface
Fig. 1. Morphology of thin nano-HA coatings fired at 400 °C
for 2 h
- Haut: Organic sol– gel coating,
- Bas: Inorganic sol coating.
Cours Polytech Orsay Chapitre 2 Prothèse – TiO2 07/10/2010 21
Fig. 3 exhibits the grazing-incidence XRD patterns of both HA
coatings on titanium by firing at 400 °C for 2 h.
From the XRD pattern, CaTiO3 did not form on Ti surface or the
interface after firing at 400–600 °C.
For all coatings after firing over 400 °C, the main crystalline
phase of coatings was calcium phosphate with apatite structure, and
no obvious tricalcium phosphate (-TCP and -TCP) and calcium
oxide were found in the XRD patterns.
Taille des cristalites : Precursor types of HA coating significantly
affected the aggregating size of particles of nano-HA coatings, which
were 25–40 nm for organic sol–gel and approximately 100 nm for
inorganic sol.
Cours Polytech Orsay Chapitre 2 Prothèse – TiO2 07/10/2010 22
Distribution de taille de cristallites
Cours Polytech Orsay Chapitre 2 Prothèse – TiO2 07/10/2010 23
SEM micrograph show the morphology of Sectioned interface
between coating and titanium fired at 400 °C for 2 h
- Haut: Organic sol –gel coating
- Bas: Inorganic sol coating.
Reste à effectuer une étude sur la biocompatibilité
Cours Polytech Orsay Chapitre 2 Prothèse – TiO2 07/10/2010 24
Chapitre 2.14 Modification de la morphologie des
cristaux d’apatites déposés31
Hydroxyapatite (HA) coatings were deposited on commercially pure
titanium plates using a hydrothermal–electrochemical deposition method in an
electrolyte containing calcium and phosphate ions. The deposition conditions
used in this study were the followings: electrolyte temperature (33–20 °C),
current density (1–2 mA/cm2), and deposition time (10–120 min).
Needle-like and granular crystals of apatite coating were created
with different concentrations of calcium (0.0021–0.042 M) and phosphate
(0.00125–0.025 M) salts.
The size of HA crystals of the coating was considerably changed with
different concentration of calcium and phosphate salts, temperature of the
electrolyte, and deposition time.
31. Yousefpour et al., Nano-crystalline growth of electrochemically deposited apatite coating
on pure titanium, Journal of Electroanalytical Chemistry 589 (2006) 96–105
Cours Polytech Orsay Chapitre 2 Prothèse – TiO2 07/10/2010 25
Chapitre 2.15 greffage à la surface de
prothèse en titane32
Pratique médicale & Contamination : Once manufactured,
prostheses are not generally hermetically sealed during shipping, and directions
to the surgeon indicate they should only be autoclaved prior to insertion; this
does not remove the surface contamination. This surface contaminant,
containing principally carbon and oxygen (in the form of native oxide and
partially oxidized hydrocarbon), also contains trace impurity ions, as shown in
the present study.
While the contaminant layer appears to be well tolerated by the
body33,34,35
, there is abundant evidence that it adheres poorly to human hard
tissue, as in the case of dental implants36
.
32. Poulin et al., The cleaning and thiolation of commercial titanium for use in dental
prostheses, Applied Surface Science 143 (1999) 238-244.
33. T. Albrektsson, Crit. Rev. Biocompat. 1 (1984) 53. 34. B. Kasemo, J. Lausmaa, Crit. Rev. Biocompat. 2 (1986) 335.
35. J. Lausmaa, J. Electron Spectrosc. Rel. Phenom. 81 _1996.343.
36. P. Ducheyne, K.E. Healy, in: B.D. Ratner _Ed.., Surface Characterization of Biomaterials,
Elsevier, New York, 1988, p. 175.
Cours Polytech Orsay Chapitre 2 Prothèse – TiO2 07/10/2010 26
An ideal situation would be one in which chemical bonding is established
across the prosthesis hard tissue interface, from titanium to bone, using an
adhesion promoter. This requires several steps, including
1. the efficient cleaning of the as-received implant to expose the reactive
titanium surface,
2. the bonding of one end of a bifunctional adhesion promoter to the
reactive surface
3. the incorporation of the other function into the hard tissue.
To clean the polycrystalline commercial titanium in the present study, we
chose to use potentiostatic anodic (rather than cathodic) polarization because
anodic reactions lead to a more efficient removal of titanium oxide, a major
surface contaminant. Surfaces cleaned in this manner were thiolated with
octadecyl thiol, C12H37SH, a simple thiol having no other reactive groups.
Cours Polytech Orsay Chapitre 2 Prothèse – TiO2 07/10/2010 27
Chapitre 2.16 Traitement de surface
d’une prothèse en titane37
Surface modification of titanium implants by introducing a titania layer on
their surface is an effective approach to provide bioinert titanium with
bioactivity, i.e., the ability to bond directly and tightly to the surrounding hard
tissue through the formation of a thin layer of apatite after implantation in the
human body.
The crystalline structure and abundance of Ti–OH functional groups have
been found to contribute to the ability of TiO2 gel to initiate apatite deposition
on titanium in human physiological fluid.
First step : In the current investigation, an amorphous TiO2 gel was
firstly introduced on titanium surface by oxidizing the titanium substrate with
hydrogen peroxide.
Second step : Well-crystallized anatase TiO2films incorporated with
abundant Ti–OH groups were then produced simply through a subsequent hot
water aging of the amorphous titania TiO2 gel.
Results obtained in this investigation suggested that the low-temperature
crystallization of titania proceeded in a dissolution–precipitation process.
Titanium treated by the present low-temperature chemical modification
technique induced significant apatite deposition within 24 h in a simulated body
fluid.
37. Wu et al., Crystallization of amorphous titania gel by hot water aging and induction of in
vitro apatite formation by crystallized titania, Surface & Coatings Technology 201 (2006)
755–761
Cours Polytech Orsay Chapitre 2 Prothèse – TiO2 07/10/2010 28
Surface morphology of CPTi oxidized by H2O2 solution at 20 °C for 2
h (a, b), followed by hot water aging at 20 °C for 72 h (c, d).
Figs. 1–3 show surface morphologies of CPTi after soaking in the H2O2 solution
at 20 °C for 2, 2 and 72 h, before and after hot water aging.
Oxidizing CPTi for 2 h in the H2O2 solution resulted in a porous titania gel layer
with cracks on the surface (Fig. 1a). The wall of the pores appeared to be
smooth at a high magnification (×40,000) (Fig. 1b).
After hot water aging, cracks disappeared (Fig. 1c), the porous network
collapsed, and the layer consisted mainly of tiny particles having sizes of tens of
nanometers (Fig. 1d).
Cours Polytech Orsay Chapitre 2 Prothèse – TiO2 07/10/2010 29
Surface morphology of CPTi oxidized by H2O2 solution at 20 °C for 2 h and
aged in hot water at 20 °C for 72 h, followed by SBF-soaking for a) 24 h and b)
42 h.
Well-crystallized anatase thin films with excellent in vitro bioactivity
could be produced on titanium surfaces by soaking the titanium substrate in 30
mass% H2O2 solution at 20 °C for 2 to 72 h, followed by a hot water aging at 20
°C for 72 h. During hot water aging, the amorphous titania gel produced by
H2O2 oxidation hydrolyzed and re-precipitated back to the substrate to form
anatase nanocrystals. Titanium treated by the present low temperature chemical
modification technique could induce apatite formation in the simulated body
fluid within 24 h.
Cours Polytech Orsay Chapitre 2 Prothèse – TiO2 07/10/2010 30
Chapitre 2.17 Processus d’interaction
possible entre le titane et l’apatite
The electronic structure of Ti-substituted hydroxyapatite is investigated
using density functional theory within a periodic slab model. Two sorption
mechanisms have been considered: i.e., Ti4+
and Ti(OH)22+
as the likely species
to exchange with Ca2+
.
Ti4+
has a small ionic radius compared to Ca2+
and can dope into both
distinct sites, showing no site preference; however, when two H were removed
from the OH channel to obtain charge compensation, preferential site II
substitution appears, accompanied with a large O shift forming a strong Ti–O
bond.
Cours Polytech Orsay Chapitre 2 Prothèse – TiO2 07/10/2010 31
The species Ti(OH)2
2+ displays a strong site preference:
substitution by Ti(OH)22+
on the hydroxyl channel (site II) is exothermic and
favored strongly over the Ca column (site I). Ti(OH)22+
substitution for Ca2+
induces a large geometry relaxation and distortion, especially within the OH
channel and Ca2+
column, with a considerable shift of Ti compared to the Ca
sites in pure HA. These results are consistent with the experimental observation
that material synthesis with high Ti doping (atomic ratio 4 0.1) shows irregular
particles formation with reduced crystallinity. The calculated cell shape and
volume relaxations indicate that the volume and cell parameters both expand in
all the substituted HA models. The site preference and volume expansion
differences found are attributed to the metal ion shift caused in meeting th
erequirement of strong Ti–O coordination in site I and site II polyhedra.
Cours Polytech Orsay Chapitre 2 Prothèse – TiO2 07/10/2010 32
Chapitre 2.12 Etude de la surface d’un
implant réel38
Due to a too complicated implant geometry (Fig. 1) to perform a
quantitative adhesion test and in order to test the adhesion of the BAG-coating
in a representative way, a simplified geometry for the adhesion test samples
(Fig. 2A), based on that of the oral implant (Fig. 1), is chosen. The oral and test
substrate have the same thermal mass to guarantee that both substrates will have
a comparable coating when using identical spraying parameters.
38. Schrooten et al., Adhesion of bioactive glass coating to Ti6Al4V oral implant,
Biomaterials 21 (2000) 1461-1469.
Cours Polytech Orsay Chapitre 2 Prothèse – TiO2 07/10/2010 33
BAG-coated Ti6Al4V test rod (A), shear test sample (B) and moment
test sample (C).
Cours Polytech Orsay Chapitre 2 Prothèse – TiO2 07/10/2010 34
SEM-micrograph of the coating cross-section of a BAG-
coated moment test sample, tested beyond its functionality.
SEM-micrograph of the BAG}Ti6Al4V interface after
adhesion testing.
Cours Polytech Orsay Chapitre 2 Prothèse – TiO2 07/10/2010 35
Chapitre 2.6 Autres applications
Chapitre 2.6a TiO2 comme agent anticancéreux39
The photocatalytic properties of TiO2-mediated toxicity have been shown
to eradicate cancer cells40,41
. It is now well established that TiO2 particles,
on exposure to ultraviolet (UV) light, produce electrons and holes leading
subsequently to the formation of reactive oxygen species ROS such as
hydrogen peroxide, hydroxyl radicals, and superoxides42
.
These oxygen species are highly reactive with cell membranes and the
cell interior, with damaged areas depending on particle location upon excitation.
Such oxidative reactions affect cell rigidity and chemical arrangement of surface
structures, leading to cell toxicity43.
Despite promising outcomes in killing cancer cells, such treatments would
be difficult to implement in clinical settings for the following reasons.
- First, UV light cannot penetrate deeply into human tissues,
thus limiting this technique to superficial tumors44
.
- Second, UV-mediated production of ROS has a very short life span
and thus would not be able to provide a continuous prolonged cancer-killing
effect.
39. Thevenot et al., Surface chemistry influences cancer killing effect of TiO2 nanoparticles,
Nanomedicine: Nanotechnology, Biology, and Medicine 4 (2008) 226–236
40. Huang N-P, Xu M-H, Yuan C-W, Yu R-R. The study of the photokilling effect and
mechanism of ultrafine TiO2 particles on U937 cells. J Photochem Photobiol A: Chem
1997;108(2-3):229-33.
41. Zhang AP, Sun YP. Photocatalytic killing effect of TiO2 nanoparticles on LS-174-T
human colon cancer cells. World J Gastroenterol 2004; 10(21):3191-3.
42. Ogino C, Farshbaf Dadjour M, Takaki K, Shimizu N. Enhancement of sonocatalytic cell
lysis of Escherichia coli in the presence of TiO2. Biochem Eng J 2006;32(2):100-5.
43. Blake DM, Maness P-C, Huang Z,Wolfrum EJ, Huang J. Application of the photocatalytic
chemistry of titanium dioxide to disinfection and the killing of cancer cells. Sep Purif
Methods 1999;28(1):1-50.
44. Cai R, Kubota Y, Shuin T, Sakai H, Hashimoto K, Fujishima A. Induction of cytotoxicity
by photoexcited TiO2 particles. Cancer Res 1992;52(8):2346-8.
Cours Polytech Orsay Chapitre 2 Prothèse – TiO2 07/10/2010 36
In the present study the nonphotocatalyic anticancer effect of surface-
functionalized TiO2 was examined. Nanoparticles bearing -OH, -NH2, or
-COOH surface groups were tested for their effect on in vitro survival of
several cancer and control cell lines.
High-resolution TEM picture of a 5-nm plasma-generated film deposited on a
25-nm nanoparticle, illustrating the uniform and highly conformal aspect of the
coating.
Cours Polytech Orsay Chapitre 2 Prothèse – TiO2 07/10/2010 37
Visualization of the interaction between TiO2 particles (0.01 mg/mL) and 3T3
cells. Cells were imaged using phase contrast after 3 hours of exposure.
(A) Nonexposed cells appear normal,
(B) exposed cells show collection of particles on the cell membrane.
Cours Polytech Orsay Chapitre 2 Prothèse – TiO2 07/10/2010 38
TiO2 particles were covered with thin polymer films of di (ethylene glycol) vinyl
ether (EO2V, -OH), allyamine (AA, -NH2), and vinyl acetic acid (VAA, -
COOH).
Cours Polytech Orsay Chapitre 2 Prothèse – TiO2 07/10/2010 39
Conclusion : Cell viability was observed to depend on particle
concentrations, cell types, and surface chemistry. Specifically, -NH2
(AA) and -OH (EO2V) groups showed significantly higher toxicity than –
COOH (VAA).
Microscopic and spectrophotometric studies revealed nanoparticle-
mediated cell membrane disruption leading to cell death.
The results suggest that functionalized TiO2, and presumably other
nanoparticles, can be surface engineered for targeted cancer therapy.
Cours Polytech Orsay Chapitre 2 Prothèse – TiO2 07/10/2010 40
Chapitre 2.6b TiO2 comme agent antibactérien45
TiO2 nanoparticles containing Ag+ have been widely used as a filler in the
manufacture of antibacterial plastics, coatings, functional fibers, dishware and
medical facilities, because Ag+ has a strong antibacterial activity against many
kinds of bacteria even at lower concentrations46,47
. However, their agglomeration
and incompatibility with organic matrix can result in the deterioration of their
mechanical properties and decrease their antibacterial property, which limits
their efficient use in antibacterial materials. Fortunately, these drawbacks could
be suppressed by surface modification of inorganic nanoparticles.
The basic material used for this study – antibacterial TiO2/Ag+
nanoparticles – is a commercial product (Shanghai Weilai Company, China)
with the primary particle size of about 70 nm and the Ag+ content approximately
0.4% by weight. Silane coupling agent, g-aminopropyltriethoxysilane (APS)
was obtained from Nanjing Shuguang Chemical Works, China.
For the preparation of composite, PVC powder (WS-1000S) was
purchased from Shanghai Chlor-Alkali Chemical Co., China. Other chemicals
used were of analytical reagent grade. Water used in this investigation was de-
ionized.
45. Cheng et al., Surface-modified antibacterial TiO2/Ag+ nanoparticles: Preparation and
properties, Applied Surface Science 252 (2006) 4154–4160
46. N. Edwards, S.B. Mitchell, A. Pratt, European Patent Application EOS251.783 (1987).
47. M. Kawashita, S. Tsuneyama, F. Miyaji, et al. Biomaterials 21 (2000) 393.
Cours Polytech Orsay Chapitre 2 Prothèse – TiO2 07/10/2010 41
The morphology of modified nanoparticles was determined by Transmission
electron microscopy (TEM). It is obvious that the particles without
modification easily agglomerate (a) whereas the modified type is
well-dispersed (b), with the particle size of approximately 70 nm.
Unmodified particles create aggregates of the size of thousands of
nanometers, and distinct particles can hardly be observed. The treated
particles, on the other hand, are apart, which proves the positive effect of
surface treatment on the particle dispersion.
Cours Polytech Orsay Chapitre 2 Prothèse – TiO2 07/10/2010 42
The bacteriostatic ratio of composites with 1.5 phr modified TiO2/Ag+
nanoparticles to bacteria was also examined. The data in Table 3 shows that the
composites have higher bacteriostatic ratio to Staphylococci (ATCC6532) than
to Escherichia coli (2099). The results further suggest that the composites have
good antibacterial properties.
Conclusions Grafted antibacterial TiO2/Ag
+ nanoparticles were prepared and tested by
various methods with the following conclusions:
(1) APS is chemically bonded on the surface of inorganic particles, the
layer thickness being ca. 25 nm.
(2) Surface treatment of the particles does not deteriorate
antibacterial properties of TiO2/Ag+ nanoparticles.
(3) Surface modification can assure better affinity of the particles to
organic matrix, in our case PVC.
These facts indicate that polymer composites with APS-grafted TiO2/Ag+
nanoparticles could be used for the manufacturing of products with antibacterial
properties in various areas (medicine, food packaging, etc.). Determination of
mechanical and other properties of the composites, however, is a research task
for the future.
Cours Polytech Orsay Chapitre 2 Prothèse – TiO2 07/10/2010 43
Chapitre 2.6c TiO2 comme microfabricated
medical device48
The use of cluster-assembled TiO2 films as cell culture substrates is of
particular interest for the coupling of cultured cells on microfabricated devices,
since it is fully compatible with planar microfabrication technologies49,50
and
it allows the deposition of patterns with submicrometric lateral resolution51
,52
.
This material can be a very interesting substrate for different applications
requiring the integration of cell cultures on micro- and nano devices and arrays.
Cluster-assembled TiO2 thin films are optically transparent and free of
defects causing visible light scattering. Therefore, they are also particularly
suited for high resolution and confocal microscopy characterizations.
TEM micrograph of a region of a cluster-assembled TiO2 film. The film is
mainly amorphous, with nanocrystalline inclusions whose size ranges from 50 to
100nm to less than 10 nm. Both rutile and anatase nanocrystals are observed.
48. Carbon et al., Biocompatibility of cluster-assembled nanostructured TiO2 with primary
and cancer cells, Biomaterials 27 (2006) 3221–3229.
49. Shin H, Jo S, Mikos A. Biomimetic materials for tissue engineering. Biomaterials
2003;24(24):4353–64.
50. Hubbell J. Materials as morphogenetic guides in tissue engineering. Curr Opin Biotechnol
2003;14(5):551–8.
51. Mazza T, Barborini E, Kholmanov IN, Piseri P, Bongiorno G, Vinati S, et al. Libraries of
cluster-assembled titania films for chemical sensing. Appl Phys Lett 2005;87:103–8.
52. Barborini E, Piseri P, Podesta A, Milani P. Cluster beam microfabrication of patterns of
three-dimensional nanostructured objects. Appl Phys Lett 2000;77:1059–61.
Cours Polytech Orsay Chapitre 2 Prothèse – TiO2 07/10/2010 44
This new biomaterial supports normal growth and adhesion of primary
and cancer cells with no need for coating with ECM proteins.
Cours Polytech Orsay Chapitre 2 Prothèse – TiO2 07/10/2010 45
Chapitre 2.6d TiO2 comme désinfectant53
Particularly in microbiological laboratories and areas of intensive medical
use, regular and thorough disinfection of surfaces is required in order to reduce
the numbers of bacteria and to prevent bacterial transmission.
Conventional methods of manual disinfection with wiping are not
effective in the longer term, cannot be standardized, and are time-intensive and
staff-intensive. In addition, there are problems associated with the use of
aggressive chemicals54
.
A potential alternative may be provided by substrates made of light-
guiding materials, coated with specific semiconductors and stimulated by
indirect mild ultraviolet A (UVA) light (320–400 nm). This method shows
oxidative and disinfectant activity. The semiconducting materials about which
most information is available is titanium dioxide (TiO2).
53. Kuhn et al., Disinfection of surfaces by photocatalytic oxidation with titanium dioxide and
UVA light, Chemosphere 53 (2003) 71–77
54. Hahn, A., Michalak, H., Bergemann, K., Heinemeyer, G., Gundert-Remy, U., 1997.
AArtzliche Mitteilungen bei Vergiftungen nach x 16e Chemikaliengesetz 1997.
Dokumentations- und Bewertungsstelle f€ur Vergiftungen im bgvv.
Cours Polytech Orsay Chapitre 2 Prothèse – TiO2 07/10/2010 46
Cours Polytech Orsay Chapitre 2 Prothèse – TiO2 07/10/2010 47
Chapitre 2.6e TiO2 pour stopper des
hémorragies55
Blood is a fluid that can flow out of an injured vessel and so be lost. To
provide sustained hemostasis, or tissue sealing, blood clots must possess
mechanical properties capable of resisting forces, such as shear, that might
otherwise break or tear the clot.
The ability to rapidly stem hemorrhage in trauma patients significantly
impacts their chances of survival, and hence is a subject of ongoing interest in
the medical community. Herein, we report on the effect of biocompatible TiO2
nanotubes on the clotting kinetics of whole blood.
55. Roy et al., The effect of TiO2 nanotubes in the enhancement of blood clotting for the
control of hemorrhage, Biomaterials 28 (2007) 4667–4672
Cours Polytech Orsay Chapitre 2 Prothèse – TiO2 07/10/2010 48
FESEM images of a 10 mm long TiO2 nanotube array achieved by
anodization of a Ti foil sample in a 2% HF in dimethyl sulfoxide
(DMSO) electrolyte; shown are cross-section, top, and bottom. The
DMSO fabricated tubes are loosely bound, and could be separated by
sonication of the sample (ethanol–water mixture) for approximately
10 s.
Figure (lower right) shows some dispersed tubes.
Cours Polytech Orsay Chapitre 2 Prothèse – TiO2 07/10/2010 49
Magnetoelastic sensors were used to quantify the blood clotting56
. Briefly,
magnetoelastic sensors are rectangular strips of ferromagnetic amorphous alloys,
which generate longitudinal elastic waves when exposed to a time varying
magnetic field57
. The frequency and amplitude of these waves at resonance
depends on the viscosity (liquid) or elasticity (solid) of the medium surrounding
the sensor58
.
Time variation in sensor resonance amplitude when immersed in pure blood, nanoparticle
containing blood, and blood containing nanotubes of varying concentrations. A 5% of the data
points are shown. Similar results are obtained for blood in contact with a nanotube/particle
decorated gauze bandage.
The TiO2 nanotubes appear to act as a scaffold, facilitating fibrin formation. Our
results suggest that application of a TiO2 nanotube functionalized bandage could
be used to help stem or stop hemorrhage.
56. Grimes CA, Ong KG, Loiselle K, Stoyanov PG, Kouzoudis D, Liu Y, et al.
Magnetoelastic sensors for remote query environmental monitoring. J Smart Mater Struct
1999;8:639–46.
57. de Lacheisserie E duT. Magnetostriction: theory and applications of magnetoelasticity. In:
Handbook of chemistry and physics. New York: CRC Press; 1993.
58. Grimes CA, Ong KG, Loiselle K, Stoyanov PG, Kouzoudis D, Liu Y, et al.
Magnetoelastic sensors for remote query environmental monitoring. J Smart Mater Struct
1999;8:639–46.
Cours Polytech Orsay Chapitre 2 Prothèse – TiO2 07/10/2010 50
Chapitre 2.7 Toxicité des
nanoparticules de TiO259,60
Recently, the potential impacts of nanomaterials on human and the
environment have attracted great attention of scientists, industries and regulatory
issues of governments 61,62,63,64
.
Some pioneering work has explored the adverse health effects of ultrafine
and fine TiO2 particles. They revealed the increased neutrophils and phagocytes
in bronchoalveolar lavage (BAL) fluid and lactate dehydrogenase (LDH)
leakage in the lung of rats and mice after exposure to TiO2 particles6566
, the
sunlight-illuminated TiO2 catalyzed DNA damage in vitro67
.
59. C. Vamanu et al., Induction of cell death by TiO2 nanoparticles: Studies on a human
monoblastoid cell line Toxicology in Vitro 22 (2008) 1689–1696.
60. Wang et al., Potential neurological lesion after nasal instillation of TiO2 nanoparticles in
the anatase and rutile crystal phases, Toxicology Letters 183 (2008) 72–80.
61. Colvin, V.L., 2003. The potential environmental impact of engineered nanomaterials. Nat.
Biotechnol. 21 (10), 1166–1170.
62. Donaldson, K., Stone, V., Tran, C.L., Kreyling,W., Borm, P.J.A., 2004. Nanotoxicology:
a new frontier in particle toxicology relevant to both the workplace and general environment
and to consumer safety. Occup. Environ. Med. 61, 727–728.
63. Nel, A., Xia, T., Mädler, L., Li, N., 2006. Toxic potential of materials at the nanolevel.
Science 311 (3), 622–627.
64. Oberdörster, G., Utell, M.J., 2002. Ultrafine particles in the urban air: to the respiratory
tract and beyond? Environ. Health Perspect. 110A, 440–441.
65. Oberdörster, G., Ferin, J., Gelein, R., Soderholm, S.C., Finkelstein, J., 1992. Role of the
alveolar macrophage in lung injury: studies with ultrafine particles. Environ. Health Perspect.
97, 193–199.
66. Bermudez, E., Mangum, J.B., Wong, B.A., Asgharian, B., Hext, P.M., Warheit, D.B.,
Everitt, J.I., 2004. Pulmonary responses of mice, rats, and hamsters to subchronic inhalation
of ultrafine titanium dioxide particles. Toxicol. Sci. 77, 347–357.
67. Wamer,W.G., Yin, J.,Wei, R., 1997. Oxidative damage to nucleic acids photosensitized
by titanium dioxide. Free Radic. Biol. Med. 23, 851–858.
Cours Polytech Orsay Chapitre 2 Prothèse – TiO2 07/10/2010 51
Prothesis
Titanium either pure or in alloys is extensively used for a wide range of
implanted medical devices, such as
dental implants,
joint replacements,
cardiovascular stents,
spinal fixation devices,
due to its advantageous combination of physico-chemical and biological
properties.
However, under mechanical stress or altered physiological
conditions such as low pH, Ti-based implants can release large
amounts of particle debris, both in the micrometer and nanometer
size range 68, 69,70
.
68. Brien, W.W., Salvati, E.A., Betts, F., Bullough, P., Wright, T., Rimnac, C., Buly, R.,
Garvin, K., 1992. Metal levels in cemented total hip arthroplasty. A comparison of well-fixed
and loose implants. Clinical Orthopaedics and Related Research, 66–74.
69. Buly, R.L., Huo, M.H., Salvati, E., Brien, W., Bansal, M., 1992. Titanium wear debris in
failed cemented total hip arthroplasty. An analysis of 71 cases. The Journal of Arthroplasty 7,
315–323.
70. Arys, A., Philippart, C., Dourov, N., He, Y., Le, Q.T., Pireaux, J.J., 1998. Analysis of
titanium dental implants after failure of osseointegration: combined
histological, electron microscopy, and X-ray photoelectron spectroscopy approach. Journal of
Biomedical Materials Research 43, 300–312.
Cours Polytech Orsay Chapitre 2 Prothèse – TiO2 07/10/2010 52
Chapitre 2.7a Toxicité des nanoparticules de TiO2 – Réponse cellulaire
The cellular responses to degradation products from titanium (Ti) implants are
important indicators for the biocompatibility of these widely used implantable
medical devices. The potential toxicity of nanoparticulate matter released from
implants has been scarcely studied.
The aim of this study was to investigate the potential of TiO2 nanoparticles
to induce modifications characteristic for death by apoptosis and/or necrosis in
U937 human monoblastoid cells.
Electron micrographs of U937 cells after 42 h exposure to (A) 4 mg/ml nano-
TiO2 – note pseudopodia (black arrow) embracing small nano-TiO2 aggregates
(white arrow), (B) 2 mg/ml nano-TiO2 – note cell with vacuole containing small
nano-TiO2 aggregates and (C) the same vacuole at higher magnification – note
presence of nano-TiO2 inside the vacuole and outside the cell (arrows).
Cours Polytech Orsay Chapitre 2 Prothèse – TiO2 07/10/2010 53
Scanning transmission electron microscopy of cells after 42 h exposure to 2
mg/ml nano-TiO2. (A) Apoptotic cell with nano-TiO2 (arrow), (B) higher
magnification of (A), (C), (D) single nanoparticles inside cytoplasm. Particles
(arrow) are not present in a vacuole. All particles were confirmed to consist of
Ti by spot energy-dispersive X-ray analyses, indicated by a white cross on A, B,
and C.
TiO2 nanoparticles induced both apoptotic and necrotic
modifications in U937 cells.
Cours Polytech Orsay Chapitre 2 Prothèse – TiO2 07/10/2010 54
Chapitre 2.7b Par inhalation71
This study was designed to determine whether ultrafine-TiO2 particles
impart significant toxicity in the lungs of rats, and more importantly, how the
activity of different TiO2 formulations compares with other reference particulate
materials, such as anatase/rutile ultrafine-TiO2 particles.
Thus, the aim was to assess in rats, using a well-developed short-term
pulmonary bioassay, the pulmonary toxicity effects of two intratracheally
instilled, ultrafine-TiO2 particle samples and to compare the lung toxicity
responses of these samples with
71. Warheit et al., Pulmonary toxicity study in rats with three forms of ultrafine-TiO2
particles: Differential responses related to surface properties, Toxicology 230 (2007) 90–104
Cours Polytech Orsay Chapitre 2 Prothèse – TiO2 07/10/2010 55
Cours Polytech Orsay Chapitre 2 Prothèse – TiO2 07/10/2010 56
The responses to uf-1, uf-2 or F-1 TiO2 particles were substantially less active in
terms of inflammation, cytotoxicity, and fibrogenic effects when compared to
the quartz, or to the uf-3 TiO2 particles.
Cours Polytech Orsay Chapitre 2 Prothèse – TiO2 07/10/2010 57
Chapitre 2.7c A travers la peau72
Skin is the largest organ of the body and serves as a primary outer layer of
environmental and/or occupational exposure. It is also an important route of
entry for foreign articles including nanomaterials into the body.
The exposure of nanoscale TiO2 to the skin can be either intentional or
accidental.
For example, in certain lotions or creams, nanoscale TiO2 is
incorporated as a sunscreen component or used to coat fibrous materials and
enhance water or as a stain repellent property. Therefore the application of the
nanoparticles to human skin is intentional.
On the other hand, dermal contact with anthropomorphic
substances during nanomaterial manufacture or combustion can be accidental.
Due to the extremely small size of nanoparticles, assessment of health risks and
toxicity of nanoscale TiO2, in particular, following a long term dermal exposure,
is a key area of study in nanotechnology.
Control des tailles par TEM
72. Wu et al.,Toxicity and penetration of TiO2 nanoparticles in hairless mice and porcine skin
after subchronic dermal exposure, Toxicology Letters 191 (2009) 1–8
Cours Polytech Orsay Chapitre 2 Prothèse – TiO2 07/10/2010 58
TEM image of nano-TiO2 particles.
(A) TiO2 10 nm;
(B) TiO2 25 nm;
(C) TiO2 60 nm.
Cours Polytech Orsay Chapitre 2 Prothèse – TiO2 07/10/2010 59
Histopathological evaluation of the organ of hairless mice after dermal exposure
to different sized TiO2 nanoparticles for 60 days. Samples were stained with
hematoxilin and eosin (H&E) and observed at 100×. The arrows points at
pathological changes in various tissue sections.