Structure and Properties of La2O3-TiO2 Nanocomposite Films for Biomedical Applications

The hemocompatibility of La2O3-doped TiO2 films with different concentration prepared by radio frequency (RF) sputtering was studied. The microstructures and blood compatibility of TiO2 films were investigated by scan electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), and UV-visible optical absorption spectroscopy, respectively. With the increasing of the La2O3 concentrations, the TiO2 films become smooth, and the grain size becomes smaller. Meanwhile, the band gap of the samples increases from 2.85 to 3.3 eV with increasing of the La2O3 content in TiO2 films from 0 to 3.64%. La2O3-doped TiO2 films exhibit n-type semiconductor properties due to the existence of Ti2+ and Ti3+. The mechanism of hemocompatibility of TiO2 film doped with La2O3 was analyzed and discussed.


Introduction
With the advancement of organ transplantation, biocompatibility, particularly blood compatibility, becomes the most important property required for biomedical materials. It is desired to develop new biomaterials with good physical, mechanical properties and hemocompatibility. Recent studies have shown that TiO 2 films are suitable as surface coatings on biomedical applications due to its good hemocompatibility [1,2], and researches concerning biomedical aspects are widely increasing [3][4][5]. The emphases of blood compatible materials research are divided into two aspects, one is the surface properties, and the other is the band and electron structure of the biomedical materials.
It is believed that the first step after blood contacting with the biomaterial is adsorption of plasma protein, which will determine the anticoagulation property of the biomaterial. In our previous paper [6], we studied the surface properties of La 2 O 3 -doped TiO 2 films and investigated the interaction between the material surface and plasma proteins. In this paper, we do the farther work and try to achieve deeper understanding of the mechanisms which are involved in blood-biomaterial interaction by investigating the influence of various La 2 O 3 concentrations on the electronic structure and hemocompatibility of TiO 2 nanocomposite films.

Preparation of Thin
Films. The La 2 O 3 -doped TiO 2 films were prepared by the radio frequency (13.56 MHz) magnetron sputtering technique. The n-type Si (100) and quartz were used as the substrates. The targets were mechanically mixed by using TiO 2 powder (in purity 99.9%) and La 2 O 3 powder (in purity 99.5%) with the La 2 O 3 molar concentration of 0%, 1%, 2%, and 3%, respectively. The substrates were ultrasonically cleaned in acetone and then were mounted on the substrate holder. After being evacuated to a base pressure of 3 × 10 −3 Pa, the working chamber was filled with Ar (99.99% purity) and the Ar gas flow was kept constant at 12 SCCM during the deposition process. The samples were prepared in room temperature with a typical work pressure of 4 Pa. The RF power of 200 W was applied in the sputtering process. The samples S1, S2, S3, and S4 are prepared using the targets with a doped La 2 O 3 molar content of 0%, 1%, 2%, and 3%, respectively.

Characterization of Thin Films.
Scanning electron microscopy (SEM, QUANTA 400F) was employed to characterize the surface topography of the TiO 2 nanocomposite films. The compositions were analyzed by X-ray photoelectron spectroscopy (XPS, ESCALAB 250, UK). The XPS spectra were recorded using Mg K α (1253.6 eV) X-ray source. The binding energy of the Au 4f 7/2 core level electron is taken to be 84.0 eV for energy calibration. Spectra were recorded with 20 eV pass energy for the survey scan and with 10 eV pass energy for the La 3d and Ti 2p regions. High resolution XPS conditions have been fixed: "fixed analyser transmission" analysis mode, a 7 × 20 mm entrance slit and 150 W electron beam power. A takeoff angle of 90 • from the surface was employed. The spectra were fitted using the Casa XPS v.2.3.13 Software (Casa software Ltd., UK) and by applying a Gaussian/Lorentzian ratio, G/L equal to 70/30. Before measurement, Ar ion etching was performed 8 minutes with an etching rate of 0.025 nm/s in order to eliminate atmosphere contaminants. A double-beam UVvisible spectrometer was used to investigate the optical absorption of the samples. The absorption spectra (in the wavelength range of 200-700 nm) were obtained by using a bare quartz substrate to eliminate the substrate contribution.

Results and Discussion
3.1. Structure Properties. The SEM photographs of TiO 2 nanocomposite films are shown in Figure 1. The surface morphology of the films becomes smooth with increasing of the La 2 O 3 content in TiO 2 films, and the grains are uniform. Figure 2 shows the grains size of TiO 2 films decreases from 133 nm to 56 nm. These micrographs, in combination with results derived by XRD, showed in our previous paper [6], suggest that La dopant not only greatly promotes the phase transfer from anatase to rutile and enhances the crystal phase of TiO 2 with preferential growth in the direction of (110), but also can refine grain size of TiO 2 .

XPS Characterization.
The La 3d spectrum of TiO 2 nanocomposite films, showed in our previous paper [6], indicated that the La exists as  with undoped sample, the high-resolution XPS analysis of the Ti 2p region obtained on the surface of S1 and S3 was shown in Figure 3. Two pronounced features are observed at binding energies near 458.4 eV and 464.3 eV, corresponding to the Ti 2p 3/2 and Ti 2p 1/2 states, respectively. The two peaks of S1 are symmetrical, which indicates that Ti exists as Ti 4+ in TiO 2 films. It is obvious that doping La 2 O 3 not only leads to the positions of two peaks of S3 shift towards lower binding energies, but also impels a broad shoulder of the two peaks. The ratio of the area of the two peaks A(Ti 2p 1/2 )/A(Ti 2p 3/2 ) is equal to 0.7, and the splitting of the   measurements in the wavelength range of 200-700 nm. Tauc relationship αE = B(E − E g ) 2 [8] was used to evaluate the optical gap values (E g ). Figure 4 shows the plot of (αhγ) 1/2 as a function of photo energy (hγ) for the films. It is clearly seen that the optical gap varies significantly with the La 2 O 3 concentration in TiO 2 films, and E g of the samples increases from 2.85 to 3.3 eV with increasing of the La 2 O 3 content in TiO 2 films from 0 to 3.64%. It is known that the quantum confinement will affect the electronic properties if the radius of the semiconductor particle is commensurable or smaller than the Bohr radius. As for TiO 2 , the effect of quantumsized confinement is expected if the particles become smaller than 10 nm (usually 2-3 nm) [9,10]. According to the measuring results of SEM (showed in Figure 2), the increase The interaction between blood and contacting biomaterials is very complicated and the detailed mechanism of hemocompatibility of TiO 2 films is still not clear. It is demonstrated that the formation of thrombus on biomaterial is correlated with electrons transferring from the inactive state of fibrinogen to the surface of the biomaterial. During the process, fibrinogen decomposes to fibrinomonomer and fibrinopeptides. After decomposition, fibrinomonomers give rise to polymers and cross-linking and finally form an irreversible thrombus [11]. So fibrinogen plays an important role in hemostasis [12]. Not only does it participate in the coagulation cascade, but also it promotes adhesion of platelets and activates them when adsorbed onto certain solid surfaces [13]. Therefore, after the adsorption of fibrinogen, it is very important to postpone the decomposition of the protein for a biomaterial with good blood compatibility. It is related to the semiconductor property of TiO 2 films.
It is found that the optical band gap La 2 O 3 -doped TiO 2 film is about 3.3 eV, and the Ti 2+ and Ti 3+ states exist in the TiO 2 film. This makes the film exhibit n-type semiconductor properties. It is proved that fibrinogen has an electronic structure similar to an intrinsic semiconductor with a band gap of 1.8 eV. When fibrinogen adsorbs on the surface of TiO 2 films, the transfer of electrons is determined by the Fermi level of the film and fibrinogen. In order to inhibit the transfer of the electrons from fibrinogen to La 2 O 3 -doped TiO 2 film, the Fermi level of La 2 O 3 -doped TiO 2 film must be close to the bottom of the conduction band, that is to say, reducing the work function of the film. The existence of Ti 2+ and Ti 3+ exhibits this effect. Thus, the perfectly electronic characteristics such as wider band gap and lower work function due to La dopant make La 2 O 3 -doped TiO 2 films exhibit better blood compatibility.

Conclusion
This study represents the relationship between the electronic structure and hemocompatibility. With the increasing of the La 2 O 3 concentrations, the TiO 2 films become smooth, and the grain size becomes smaller. The band gap of the samples increases from 2.85 to 3.3 eV with increasing of the La 2 O 3 content in TiO 2 films from 0 to 3.64%. Based on the contact angles and platelet adsorption experiments, La 2 O 3 -doped TiO 2 films not only possess excellent surface properties of absorbing human serum albumin (HAS) preferentially, but also exhibit n-type semiconductor properties, which farther inhibit the transfer of the electrons from fibrinogen to TiO 2 films.