Synthesis and Characterization of Hierarchical Mesoporous-Macroporous TiO<sub>2</sub>-ZrO<sub>2</sub> Nanocomposite Scaffolds for Cancellous Bone Tissue Engineering Applications

Mahtabian, Shima; Yahay, Zahra; Mirhadi, Seyed Mehdi; Tavangarian, Fariborz

doi:https://doi.org/10.1155/2020/8305871

Journal of Nanomaterials

On this page

Abstract Introduction Materials and Methods Results Conclusions Data Availability Additional Points Conflicts of Interest References Copyright Related Articles

Special Issue

Applications of Nanobiomaterials in Tissue Repair

View this Special Issue

Research Article | Open Access

Volume 2020 | Article ID 8305871 | https://doi.org/10.1155/2020/8305871

Synthesis and Characterization of Hierarchical Mesoporous-Macroporous TiO₂-ZrO₂ Nanocomposite Scaffolds for Cancellous Bone Tissue Engineering Applications

Shima Mahtabian,¹Zahra Yahay,¹Seyed Mehdi Mirhadi,¹and Fariborz Tavangarian²

Academic Editor: Nicholas Dunne

Received30 Jul 2020

Revised31 Aug 2020

Accepted17 Sept 2020

Published06 Oct 2020

Abstract

Bone tissue engineering has been introduced several decades ago as a substitute for traditional grafting techniques to treat bone defects using engineered materials. The main goal in bone tissue engineering is to introduce materials and structures which can mimic the function of bone to restore the damaged tissue and promote cell restoration and proliferation. Titania and zirconia are well-known bioceramics which have been widely used in tissue engineering applications due to their unsurpassed characteristics. In this study, hierarchical meso/macroporous titania-zirconia (TiO₂-ZrO₂) nanocomposite scaffolds have been synthesized and evaluated for bone tissue engineering applications. The scaffolds were produced using the evaporation-induced self-assembly (EISA) technique along with the foamy method. To characterize the samples, X-ray diffraction (XRD), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), simultaneous thermal analysis (STA), and Brunauer-Emmett-Teller (BET) analysis were performed. The results showed that TiO₂-ZrO₂ scaffolds can be produced after sintering the samples at 550°C for 2 h. Among samples with different weight percentages of zirconia and titania, the sample containing 13 wt.% zirconia was considered as the optimum sample due to its structural integrity. This scaffold had pore size, pore wall size, and mesopores in the range of μm, μm, and 7-13 nm, respectively. The specific surface area obtained from the BET theory, total volume, and mean diameter of pores of this sample was 13.627 m²g^1-, 0.03788 cm³g^-1, and 11 nm, respectively. The results showed that the produced scaffolds can be considered as the promising candidates for cancellous bone regeneration.

1. Introduction

In recent decades, a great deal of effort and attention has been focused on designing scaffolds which are biologically, chemically, physically, mechanically, and structurally carefully matched to that of natural bone [1–23]. Although each type of bone tissue has specific requirements which must be met, there are some features in common that should be considered in designing bone scaffolds to present the exact function of host tissue [24, 25]. Generally, bone has a complex meso/macroporous hierarchical structure [24–29] with multisized interconnected pores [30, 31]. One of the main issues is to synthesize scaffolds with a hierarchical porous structure with pore interconnectivity to mimic the ECM of the host tissue. Different pore sizes play a remarkable role in enhancing cell viability and osteogenesis and finally in therapeutic effects for bone tissue engineering applications [32–36]. The macropore size of larger than 150 μm is required for cell accommodation and proliferation and also for vascularization [32, 37–42]. Mesopores with the size of 2-50 nm are also required to insert the nutrients and release the biological agents, to remove waste materials, and also to enhance the surface activity and bioactivity [37, 40–42].

Different techniques have been used to synthesize hierarchical structures including templating methods [43, 44], freeze-drying technique [45–47], and sol-gel method [48, 49]. In this study, the sol-gel method was utilized to synthesize the samples.

According to the literature, the sol-gel method is a facile way to synthesize metal oxide nanoparticles with high quality and purity at low temperatures. In this technique, precursors are dispersed in an aquatic or alcoholic environment at temperatures lower than 100°C. Through the hydrolysis and condensation, aggregation in the obtained colloidal solution which is called “sol” causes to make “gel” with a 3D network of M-O-M or M-OH-M units. Unlike other techniques such as the solid-state method, the sol-gel procedure requires low temperatures and very fine powders in which a homogeneous composition can be obtained. However, there are some disadvantages as well which should be considered such as a relatively high cost of initial precursors and the formation of cracks during the heat treatment cycles to remove the organic materials [50].

On the other hand, the evaporation-induced self-assembly technique (EISA) is a successful, simple, fast, and efficient method for the preparation of mesoporous metal oxides [51, 52]. The existence of hydrophobic and hydrophilic components in the surfactants causes the formation of micelle-like structures that are removed from the system by burning the hydrocarbon chains which leaves pores behind. This technique was first used to synthesize the silica mesoporous structure [53–55] and gradually was incorporated with the sol-gel method by using surfactants for other metal oxides [56]. Among many kinds of surfactants, the nonionic Pluronic F127 formed a well-organized mesopore structure [57].

TiO₂-ZrO₂ nanocomposite has been used in different applications. For example, Fu et al. [58] and Yu et al. [59] worked on its photocatalytic properties, individually. They reported that this nanocomposite shows better photocatalytic behavior compared to titania or zirconia, separately. The bioactivity of titania-zirconia nanocomposite has been studied by Marchi et al. [60]. The results showed an increase in apatite formation ability which indicates its good bioactivity in the biological environment. Also, this composite has been used as a 3D scaffold and coating. Tiainen et al. [61] investigated the mechanical properties of titania-zirconia nanocomposite scaffolds with different weight percentages of zirconia. The results showed that increasing the amount of zirconia in the composite decreased the mechanical strength of the scaffolds. Titania coating on its alloys is widely used in dental implants and hip prosthesis due to their excellent biocompatibility. According to the literature, TiO₂ has excellent biocompatibility, low toxicity, good corrosion resistance, and low density [62–64]. On the other hand, zirconia has several upsides over other bioceramics. Zirconia is bioinert in vivo and in vitro [65–67]. In vitro tests have shown that zirconia has lower toxicity than titanium oxide [68]. Additionally, cytotoxicity and carcinogenicity have not been reported [68]. Besides, it has good mechanical properties such as corrosion and abrasion resistance. Furthermore, it increases the crack self-healing potential of scaffolds by its transformation toughening mechanism [69, 70]. The strength of interfacial bonding between substrate and coating will be improved by the help of adding ZrO₂. Also, zirconia enhances apatite formation due to increasing the hydrophilicity of the substrate [71].

In the present study, for the first time, nanocomposite ZrO₂/TiO₂ scaffolds were produced using the EISA technique combined with the foamy method. Interconnected macropores were prepared by polyurethane (PU) (60 pores per inch (ppi)) sponge, and mesopores were made using Pluronic F127 surfactant by the help of a self-assembly technique in order to simulate the natural bone hierarchical porous structure. Structural features, chemical composition, and porosity features of the ZrO₂/TiO₂ nanocomposite scaffolds were evaluated. Furthermore, the formation mechanism of the produced scaffolds was evaluated as well.

2. Materials and Methods

2.1. Sample Preparation

In this study, the sol-gel technique was used to fabricate TiO₂-ZrO₂ nanocomposite scaffolds. A schematic representation of the sol-gel method is shown in Figure 1. To prepare the samples, titania and zirconia solutions were produced. Titania solution was prepared according to our previous study [72]. Briefly, 5 ml titanium (IV) butoxide (C₁₆H₃₆O₄Ti, 97%, Sigma-Aldrich) was added to 3.092 ml acetylacetone (C₅H₈O₂, 99.5%, Merck) and 125 ml absolute ethanol (C₂H₆O, 99.5%, Sigma-Aldrich). Next, a mixture of 2 gr Pluronic F127 (PF127, C₃H₃O [C₂H₄O][C₃H₆O][C₂H₄O]C₃H₃O₂, 99.5%, Sigma-Aldrich) that was dissolved in 125 ml absolute ethanol (C₂H₆O, 99.5%, Sigma-Aldrich) and 6.67 ml hydrochloric acid (HCL, 38 wt.%, to adjust the pH solution to 4 as the zeta potential of the solution in order to disperse the particles and avoid coagulation) was gently added to the previous solution, stirred for 24 h with the speed of 1000 rpm at room temperature, and then aged for 48 h at a location with 40% humidity.

Based on the previous study [73], to prepare zirconia solution, 3.65 ml zirconium (IV) butoxide (Zr(OC₄H₂)₄, 80 wt.%, Sigma-Aldrich) and 0.63 gr citric acid (C₆H₈O₇, Merck) were dissolved in 125 ml absolute ethanol and stirred by a magnetic stirrer until a clear solution was obtained. Then, a combination of 2 gr PF127, 125 ml absolute ethanol, and 6.67 ml hydrochloric acid was gently added to the zirconia solution, stirred for 24 h with the speed of 1000 rpm at ambient temperature, and then aged for 48 h at a location with 40% humidity. Samples with different weight ratios of titania and zirconia solutions were prepared to investigate their effect on the sample integrity and microstructure. Table 1 shows the designation and specification of different samples.

PU sponge (60 PPI) with a mean pore size of 300-700 μm was used to make blocks with a dimension of . The blocks were dipped in different solutions with various ZrO₂ to TiO₂ weight ratios for 1 h. The saturated PU blocks with the solution were squeezed by a hand roller. These blocks were then dried at room temperature for 72 h. The dried foams were sintered at 550°C for 2 h with the heating/cooling rate of 5°C min ^-1. Figure 2 illustrates the preparation steps of different samples.

2.2. Sample Characterization

In order to assess the thermal decomposition temperature of PU foam and volatile materials and to optimize the calcination temperature of materials used to make the solutions, a simultaneous thermal analysis (STA) test was performed up to 550°C with the heating rate of 5°C/min, using the NETZSCH STA 449F3 machine.

To investigate the morphology and to measure the pore size of the scaffolds, scanning electron microscopy (SEM) was applied using SEM/EDS, Zeiss, Germany machine (FEI Quanta 200 SEM) with the working distance in the range of 9.5-13.8 μm and the voltage in the range of 15 to 25 kV. To evaluate the elemental compositions of samples, energy-dispersive spectroscopy (EDS) was utilized. Map scan analyses were performed to determine the elements formed in randomly selected locations of the scaffolds using the same machine. Small-angle X-ray scattering (SAXS) was performed using the Asenware AW-DX300 diffractometer to approve the formation of a mesoporous structure. SAXS traces were recorded with 2θ in the range of 0.5-10 degrees with a Cu Kα radiation source with nm. Wide-angle X-ray diffraction (WAXRD) analysis with 2θ in the range of 10-90 degrees was used to study the crystalline phase of samples using the same machine. The nitrogen adsorption-desorption isotherms were used at 77 K using the BELSORP-mini II analyzer to determine the pore structure and to assess the specific surface area.

3. Results and Discussions

3.1. STA Evaluation

To assess the weight loss and to determine the temperature of reactions that occurred during the sintering procedure of TiO₂-ZrO₂ scaffolds, simultaneous thermal analysis (STA) was utilized. Different samples (Table 1, SS which contains only solution, SF which contains only PU foam, and SSF which contains a solution with PU foam together), 3 samples for each, were used to accurately determine the effect of each component on the STA traces. Figure 3 shows the results of the thermogravimetry-differential scanning calorimeter (TG-DSC) curves of different samples. The TG curve of the SF sample (contains only PU foam) showed that foam is burned out at a temperature of around °C (Figure 3(a)) [74]. The results proved that at the sintering temperature, no sponge was left in the structure.

(a)

(b)

(c)

Figure 3(b) shows the STA analysis of the SS sample which only contains solution A (see Table 1). The results showed that there is an exothermic peak at 301.6°C. The TGA result also showed that this exothermic process accounted for a substantial amount of the total weight loss on the whole decomposition process from about 50°C to around 300°C. The exothermic peak and the associated weight loss were due to the decomposition of organic materials and their removal from the system, as proved by the EDS analysis of the sintered scaffolds, at 550°C in which no organic material was detected (Figure 4).

The exothermic peak and subsequent mass change at around 300°C were in good agreement with the reported results of previous studies. In other words, the range of around 171.40-301.37°C has been considered as the decomposition temperature of Pluronic F127. The decomposition temperature of zirconium butoxide, acetylacetone, titanium butoxide, and citric acid was reported to be around 176.85°C, 280°C, 122°C, and 19.85-399.85°C, respectively [72, 75–80].

Also, Figure 3(c) pertains to the SSF sample, the one with both foam and solution. It can be seen that foam was removed from the system at °C. The exothermic peak occurred at °C could be ascribed to the oxidation of titanium and zirconium. Based on the results of Figure 3, the calcination temperature was adjusted to 550°C to ensure that at the end of the heat treatment cycle, no foam and organic additives were left in the scaffolds and only titanium and zirconium oxides were present in the structure.

3.2. SEM/EDS Evaluation

The morphology and pore size of the scaffolds are extremely important to achieve desirable mechanical properties and to have effective cell adhesion, cell proliferation, and strong cell growth into the scaffolds. The optimized sample in this study was known as the one with structural integrity without any cracks. To investigate the morphology of pores that have been formed through the foamy method after heat treatment and their size, samples were studied with SEM. Figure 5 shows the structure, pore morphology, pore size, pore distribution, mesopores, and finally pore wall of a random macropore of S_13Zr sample which was annealed at 550°C for 2 h. Figures 5(a) and 5(b) show the macropore structure, and Figures 5(c) and 5(d) show the mesopore structures in the scaffolds.

(a)

(b)

(c)

(d)

Figure 5

Scanning electron microscopy (SEM) images of sample S_13Zr as the optimized sample (S_13Zr) sintered at 550°C for 2 h: (a) the general shape of the scaffold which shows the favorable structural integrity, (b) acceptable pore morphology and pore size (no crack can be observed), (c) desirable size of mesopores which are the best space to insert nutrients to be used by cells in order to proliferate and grow into the scaffold, and (d) strong pore wall which exhibits nice interconnectivity and strong structure for each macropore to mimic the natural bone tissue structure.

On the other hand, Figure 6 shows the structure of other samples with different amounts of zirconia that were annealed in the same condition. As can be seen in Figure 6, all samples have some structural defects such as cracks on the wall of pores (shown by arrows). The high amount of zirconia can be the reason for the existence of cracks in the scaffolds which makes them completely useless for bone tissue engineering applications [61]. However, as can be seen in Figure 5, S_13Zr sample (containing 13 wt.% zirconia and 87 wt.% titania) exhibits an integrated structure with no crack, appropriate pore size for cell accommodation, cell growth, and cell proliferation. Therefore, S_13Zr sample was considered as the optimized sample for further studies.

(a)

(b)

(c)

(d)

Figure 7 shows the histogram of the macropore size in the S_13Zr sample. As it is obvious, the formation of appropriate macroporosity with a desirable size (more frequency in pore sizes measured greater than 150 μm that is beneficial for cell accommodation, penetration, and differentiation) in the produced scaffold can provide a suitable environment for the vascularization which plays a vital role in the success of the scaffold. EDS was utilized to reveal the average local chemical composition in the produced scaffold. Figure 4 shows the EDS results of the S_13Zr sample. A homogeneous distribution of Ti and Zr elements was observed in the EDS results of the optimized scaffold.

Figure 8 shows the results of the EDS elemental mapping of the S_13Zr sample. The results showed a homogeneous distribution of Ti and Zr in this sample which demonstrate the effectiveness of the fabrication technique to form a uniform structure.

(a)

(b)

(c)

(d)

3.3. XRD Evaluation

The phase transformation of the S_13Zr sample was investigated by XRD. Figure 9(a) illustrates the wide-angle X-ray scattering (WAXRD) pattern. The presence of metal oxide formed at the low temperature was successfully proved by the XRD patterns. As can be seen in Figure 9(a), the sample has not been completely crystallized due to the low temperature used for heat treatment. The low annealing temperature was used to protect and retain the mesopores of the sample because the mesopores will collapse during a high temperature of sintering [81]. On the other hand, the mesoporous structure transforms the long-range order of crystals into the short-range order. So the XRD pattern of mesoporous structures is similar to semicrystalline structures [81]. An intensive peak can be seen in Figure 9(a) in 2θ equals to 25 degrees that shows the formation of the anatase phase (XRD JCPDS data file No. 01-071-1169) in the structure.

(a)

(b)

Titania and zirconia can form different crystal polymorphs at different temperatures [82, 83]. According to their phase diagram and the calcination temperature, the anatase phase for titania and monoclinic phase for zirconia should be stable at room temperature [84].

Based on the literature, the monoclinic phase of zirconia is thermodynamically its most stable phase; however, the less stable phases of zirconia (cubic or tetragonal) could form at higher temperatures. In other words, according to the zirconia phase diagram, the monoclinic phase of zirconia is stable from ambient temperature to 1170°C. The tetragonal phase is stable from 1170°C to 2370°C, and from 2370°C to the melting point cubic phase of zirconia will be stable [83].

On the other hand, the most stable phase of titania is rutile; however, according to previous studies, the formation of short-range order TiO₆ in anatase is easier than the formation of long-range order TiO₆ in rutile [82]. Also, thermodynamically, the level of surface free energy of anatase is lower than that of the rutile phase which causes that TiO₂-based nanocomposites and nanofilms contain anatase phase at room temperature [82].

Some elements such as Ca, scandium, strontium, yttrium, niobium, barium, lanthanum, aurum (gold), boron, aluminum, silicon, phosphorus, sulfur, chlorine, cerium, neodymium, samarium, europium, gadolinium, terbium, dysprosium, holmium, erbium, thulium, ytterbium, and specifically zirconia have an inhibitor role against phase transformation from anatase to rutile in titania [4, 82, 85]. In this study, Zr has been used as the second phase of the nanocomposite. In fact, the addition of zirconia to titania stabilizes the anatase phase of titania and inhibits its grain growth [86].

Figure 9(b) shows the small-angle X-ray spectroscopy (SAXS) pattern of sample S_13Zr which was sintered at 550° for 2 h. In the SAXS analysis, the intensity and sharpness of the peak is a sign of the formation of a well-ordered mesoporous structure [87, 88]. SAXS was performed in the 2θ range of 0.5-10 degrees. As can be seen in Figure 9(b), a sharp peak in 2θ equals to 0.7 degrees can be observed which indicates the formation of well-ordered mesoporous structures in this sample. The results obtained from the SAXS analysis were in good agreement with those obtained from the SEM observation (Figure 5(c)).

In general, TiO₂ formation occurs in three different steps. As mentioned, the sol-gel method through the alkoxide route was used to prepare TiO₂ and ZrO₂ solutions. At the first step, the aqueous environment induces alkoxide hydrolysis and produces titanium hydroxide and zirconium hydroxide and alcohol (alkoxide group hydroxide). The second step can occur through the interaction between either two hydroxide metals or a hydroxide metal and an alkoxide metal that finally produce A-O-A, in which A refers to the metal (Zr or Ti) and O refers to the oxygen, and water or alcohol in an aqueous and alcoholic environment [89–91]. TiO₂ and ZrO₂ particles act as the nuclei to expand metal oxides formed during the synthesis procedure. The steps of the formation of TiO₂ can be expressed as follows [90]: (1)Hydrolysis of titanium alkoxide: (2)Condensation of hydrolyzed species:

Equation (2) can also be expressed as follows: (3)Growth of TiO₂ sol particles

On the other hand, almost the same procedures happen during the formation of ZrO₂ [91]: (1)Hydrolysis of zirconium alkoxide: (2)Condensation of hydrolyzed species: In more details: (3)Growth of ZrO₂ sol particles

Figure 10 shows the schematic representation of the aforementioned steps clearly in detail.

The nuclei growth phenomenon stems from the incredible high surface area of particles and consequently their high amount of energy which makes them thermodynamically unstable. For this purpose, metal oxide particles (as the nuclei) start to grow through Ostwald ripening or oriented attachment mechanism or even both, to decrease their energy level. According to Ostwald ripening phenomenon, small particles dissolve in the solution because of their high energy level and bigger particles get bigger and bigger in regular spherical shapes by attracting small particles. Based on the oriented attachment mechanism, small particles get together and aggregate at the first step; then, they will be considered as a specific place for other small particles to attach and consequently form crystals [92]. Linear F127 polymer that was used as the template for mesopores has hydrophilic and hydrophobic parts. After dissolving in ethanol, F127 forms special structures that usually transforms into regular spherical micelles in solution. Finally, drying and calcination cause the formation of mesostructure [93]. Figure 11 shows the mechanism of mesopore formation.

3.4. BET Evaluation

Figure 12 demonstrates the nitrogen adsorption-desorption isotherms of the S_13Zr sample after sintering at 550°C for 2 h. The specific surface area of the S_13Zr sample measured by the Brunauer-Emmett-Teller (BET) theory was 13.627 m²g^-1; the total porosity volume obtained from the adsorption curve of the isotherm diagram and mean pore diameter were 0.03788 cm³g^-1 and 11.119 nm, respectively.

4. Conclusions

In this study, hierarchical meso/macroporous hierarchical titania-zirconia nanocomposite was fabricated for tissue engineering applications. Different samples with different weight percentages of titania and zirconia were prepared by the help of the EISA technique coupled with the foamy method. The foamy method was applied to provide the macropore template, and the EISA method was utilized to provide a mesopore structure. The results showed that scaffolds with a lower amount of zirconia had less structural defects. This scaffold had pore size, pore wall size, and mesopores in the range of μm, μm, and 7-13 nm, respectively. The specific surface area obtained from the BET theory, total volume, and mean diameter of pores of this sample was 13.627 m²g^-1, 0.03788 cm³g^-1, and 11 nm, respectively.

Data Availability

The raw/processed data required to reproduce these findings cannot be shared at this time as the data also forms part of an ongoing study. If you need to have access to some of the raw data, please contact the corresponding author.

Additional Points

Highlights. (1) ZrO₂/TiO₂ nanocomposite scaffolds were synthesized using the EISA and foamy method. (2) The formation mechanism of the scaffolds was scrutinized. (3) The influence of the ZrO₂ on the integrity of the scaffolds was evaluated. (4) Nanocomposite scaffolds consisting of 13 wt.% ZrO₂ showed an integrated structure

Conflicts of Interest

The authors declare that there is no conflict of interest regarding the publication of this article.

References

A. R. Amini, C. T. Laurencin, and S. P. Nukavarapu, “Bone tissue engineering: recent advances and challenges,” Critical Reviews in Biomedical Engineering, vol. 40, no. 5, pp. 363–408, 2012.
View at: Publisher Site | Google Scholar
S. Bose, M. Roy, and A. Bandyopadhyay, “Recent advances in bone tissue engineering scaffolds,” Trends in Biotechnology, vol. 30, no. 10, pp. 546–554, 2012.
View at: Publisher Site | Google Scholar
K. J. L. Burg, S. Porter, and J. F. Kellam, “Biomaterial developments for bone tissue engineering,” Biomaterials, vol. 21, no. 23, pp. 2347–2359, 2000.
View at: Publisher Site | Google Scholar
C. Chen, E. Kelder, and J. Schoonman, “Electrostatic sol-spray deposition (ESSD) and characterisation of nanostructured TiO₂ thin films,” Thin Solid Films, vol. 342, no. 1-2, pp. 35–41, 1999.
View at: Publisher Site | Google Scholar
C. J. Damien and J. R. Parsons, “Bone graft and bone graft substitutes: a review of current technology and applications,” Journal of Applied Biomaterials, vol. 2, no. 3, pp. 187–208, 1991.
View at: Publisher Site | Google Scholar
P. V. Giannoudis, H. Dinopoulos, and E. Tsiridis, “Bone substitutes: an update,” Injury, vol. 36, no. 3, pp. S20–S27, 2005.
View at: Publisher Site | Google Scholar
L. G. Griffith and G. Naughton, “Tissue engineering--current challenges and expanding opportunities,” Science, vol. 295, no. 5557, pp. 1009–1014, 2002.
View at: Publisher Site | Google Scholar
L. L. Hench, “Bioceramics: from concept to clinic,” Journal of the American Ceramic Society, vol. 74, no. 7, pp. 1487–1510, 1991.
View at: Publisher Site | Google Scholar
J. Henkel, M. A. Woodruff, D. R. Epari et al., “Bone regeneration based on tissue engineering conceptions — a 21st century perspective,” Bone Research, vol. 1, no. 3, pp. 216–248, 2013.
View at: Publisher Site | Google Scholar
J. R. Jones and L. L. Hench, “Regeneration of trabecular bone using porous ceramics,” Current Opinion in Solid State and Materials Science, vol. 7, no. 4-5, pp. 301–307, 2003.
View at: Publisher Site | Google Scholar
D. C. Lobb, B. R. DeGeorge Jr., and A. B. Chhabra, “Bone Graft Substitutes: current concepts and future expectations,” The Journal of Hand Surgery, vol. 44, no. 6, pp. 497–505.e2, 2019.
View at: Publisher Site | Google Scholar
P. X. Ma, “Scaffolds for tissue fabrication,” Materials Today, vol. 7, no. 5, pp. 30–40, 2004.
View at: Publisher Site | Google Scholar
A. G. Mikos, S. W. Herring, P. Ochareon et al., “Engineering complex tissues,” Tissue Engineering, vol. 12, no. 12, pp. 3307–3339, 2006.
View at: Publisher Site | Google Scholar
R. G. Ribas, V. M. Schatkoski, T. L. d. A. Montanheiro et al., “Current advances in bone tissue engineering concerning ceramic and bioglass scaffolds: A review,” Ceramics International, vol. 45, no. 17, pp. 21051–21061, 2019.
View at: Publisher Site | Google Scholar
F. R. A. J. Rose and R. O. C. Oreffo, “Bone tissue engineering: hope vs hype,” Biochemical and Biophysical Research Communications, vol. 292, no. 1, pp. 1–7, 2002.
View at: Publisher Site | Google Scholar
A. J. Salinas, P. Esbrit, and M. Vallet-Regí, “A tissue engineering approach based on the use of bioceramics for bone repair,” Biomaterials Science, vol. 1, no. 1, pp. 40–51, 2013.
View at: Publisher Site | Google Scholar
B. D. Smith and D. A. Grande, “The current state of scaffolds for musculoskeletal regenerative applications,” Nature Reviews Rheumatology, vol. 11, no. 4, pp. 213–222, 2015.
View at: Publisher Site | Google Scholar
M. M. Stevens, “Biomaterials for bone tissue engineering,” Materials Today, vol. 11, no. 5, pp. 18–25, 2008.
View at: Publisher Site | Google Scholar
J. Vacanti, “Tissue engineering and regenerative medicine: from first principles to state of the art,” Journal of Pediatric Surgery, vol. 45, no. 2, pp. 291–294, 2010.
View at: Publisher Site | Google Scholar
W. Wang and K. W. K. Yeung, “Bone grafts and biomaterials substitutes for bone defect repair: a review,” Bioactive Materials, vol. 2, no. 4, pp. 224–247, 2017.
View at: Publisher Site | Google Scholar
S. Yang, K.-F. Leong, Z. Du, and C.-K. Chua, “The design of scaffolds for use in tissue engineering. Part I. Traditional factors,” Tissue Engineering, vol. 7, no. 6, pp. 679–689, 2001.
View at: Publisher Site | Google Scholar
X. Yu, X. Tang, S. V. Gohil, and C. T. Laurencin, “Biomaterials for bone regenerative engineering,” Advanced Healthcare Materials, vol. 4, no. 9, pp. 1268–1285, 2015.
View at: Publisher Site | Google Scholar
K. Zhang, S. Wang, C. Zhou et al., “Advanced smart biomaterials and constructs for hard tissue engineering and regeneration,” Bone Research, vol. 6, no. 1, pp. 1–15, 2018.
View at: Publisher Site | Google Scholar
M. J. Olszta, X. Cheng, S. S. Jee et al., “Bone structure and formation: A new perspective,” Materials Science and Engineering: R: Reports, vol. 58, no. 3-5, pp. 77–116, 2007.
View at: Publisher Site | Google Scholar
S. H. Ralston, “Bone structure and metabolism,” Medicine, vol. 41, no. 10, pp. 581–585, 2013.
View at: Publisher Site | Google Scholar
J. Buckwalter and R. Cooper, “Bone structure and function,” Instructional Course Lectures, vol. 36, pp. 27–48, 1987.
View at: Google Scholar
J. R. Jones, P. D. Lee, and L. L. Hench, “Hierarchical porous materials for tissue engineering,” Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences, vol. 364, no. 1838, pp. 263–281, 2006.
View at: Publisher Site | Google Scholar
J.-Y. Rho, L. Kuhn-Spearing, and P. Zioupos, “Mechanical properties and the hierarchical structure of bone,” Medical Engineering & Physics, vol. 20, no. 2, pp. 92–102, 1998.
View at: Publisher Site | Google Scholar
S. Weiner and W. Traub, “Bone structure: from ångstroms to microns,” The FASEB Journal, vol. 6, no. 3, pp. 879–885, 1992.
View at: Publisher Site | Google Scholar
J. X. Lu, B. Flautre, K. Anselme et al., “Role of interconnections in porous bioceramics on bone recolonization in vitro and in vivo,” Journal of Materials Science Materials in Medicine, vol. 10, no. 2, pp. 111–120, 1999.
View at: Publisher Site | Google Scholar
M. Mastrogiacomo, S. Scaglione, R. Martinetti et al., “Role of scaffold internal structure on in vivo bone formation in macroporous calcium phosphate bioceramics,” Biomaterials, vol. 27, no. 17, pp. 3230–3237, 2006.
View at: Publisher Site | Google Scholar
B. Feng, Z. Jinkang, W. Zhen et al., “The effect of pore size on tissue ingrowth and neovascularization in porous bioceramics of controlled architecturein vivo,” Biomedical Materials, vol. 6, no. 1, article 015007, 2011.
View at: Publisher Site | Google Scholar
V. Karageorgiou and D. Kaplan, “Porosity of 3D biomaterial scaffolds and osteogenesis,” Biomaterials, vol. 26, no. 27, pp. 5474–5491, 2005.
View at: Publisher Site | Google Scholar
C. M. Murphy, M. G. Haugh, and F. J. O'brien, “The effect of mean pore size on cell attachment, proliferation and migration in collagen–glycosaminoglycan scaffolds for bone tissue engineering,” Biomaterials, vol. 31, no. 3, pp. 461–466, 2010.
View at: Publisher Site | Google Scholar
J. Zeltinger, J. K. Sherwood, D. A. Graham, R. Müeller, and L. G. Griffith, “Effect of pore size and void fraction on cellular adhesion, proliferation, and matrix deposition,” Tissue Engineering, vol. 7, no. 5, pp. 557–572, 2001.
View at: Publisher Site | Google Scholar
W. Zhen, C. Jiang, B. Feng, S. Xiaojiang, L. Jianxi, and L. Li, “Role of the porous structure of the bioceramic scaffolds in bone tissue engineering,” Nature Precedings, 2010.
View at: Google Scholar
D. Lozano, M. Manzano, J. C. Doadrio et al., “Osteostatin-loaded bioceramics stimulate osteoblastic growth and differentiation,” Acta Biomaterialia, vol. 6, no. 3, pp. 797–803, 2010.
View at: Publisher Site | Google Scholar
J. Rouwkema and A. Khademhosseini, “Vascularization and angiogenesis in tissue engineering: beyond creating static networks,” Trends in Biotechnology, vol. 34, no. 9, pp. 733–745, 2016.
View at: Publisher Site | Google Scholar
J. Rouwkema, N. Rivron, and C. A. van Blitterswijk, “Vascularization in tissue engineering,” Trends in Biotechnology, vol. 26, no. 8, pp. 434–441, 2008.
View at: Publisher Site | Google Scholar
W. Tang, D. Lin, Y. Yu et al., “Bioinspired trimodal macro/micro/nano-porous scaffolds loading rhBMP-2 for complete regeneration of critical size bone defect,” Acta Biomaterialia, vol. 32, pp. 309–323, 2016.
View at: Publisher Site | Google Scholar
C. Wu and J. Chang, “Mesoporous bioactive glasses: structure characteristics, drug/growth factor delivery and bone regeneration application,” Review Interface Focus, vol. 2, no. 3, pp. 292–306, 2012.
View at: Publisher Site | Google Scholar
S. Yang, K. Leong, Z. du, and C. K. Chua, “The design of scaffolds for use in tissue engineering. Part II. Rapid prototyping techniques,” Tissue Engineering, vol. 8, no. 1, pp. 1–11, 2002.
View at: Publisher Site | Google Scholar
O. Sel, D. Kuang, M. Thommes, and B. Smarsly, “Principles of hierarchical meso- and macropore architectures by liquid crystalline and polymer colloid templating,” Langmuir, vol. 22, no. 5, pp. 2311–2322, 2006.
View at: Publisher Site | Google Scholar
B. Smarsly and M. Antonietti, “Block copolymer assemblies as templates for the generation of mesoporous inorganic materials and crystalline films,” European Journal of Inorganic Chemistry, vol. 2006, no. 6, pp. 1111–1119, 2006.
View at: Publisher Site | Google Scholar
S. Deville, “Freeze-casting of porous ceramics: a review of current achievements and issues,” Advanced Engineering Materials, vol. 10, no. 3, pp. 155–169, 2008.
View at: Publisher Site | Google Scholar
M. C. Gutiérrez, M. L. Ferrer, and F. del Monte, “Ice-templated materials: sophisticated structures exhibiting enhanced functionalities obtained after unidirectional freezing and ice-segregation-induced self-assembly†,” Chemistry of Materials, vol. 20, no. 3, pp. 634–648, 2008.
View at: Publisher Site | Google Scholar
L. Qian and H. Zhang, “Controlled freezing and freeze drying: a versatile route for porous and micro-/nano-structured materials,” Journal of Chemical Technology and Biotechnology, vol. 86, no. 2, pp. 172–184, 2011.
View at: Publisher Site | Google Scholar
A. Feinle, M. S. Elsaesser, and N. Hüsing, “Sol–gel synthesis of monolithic materials with hierarchical porosity,” Chemical Society Reviews, vol. 45, no. 12, pp. 3377–3399, 2016.
View at: Publisher Site | Google Scholar
A. Monnier, F. Schüth, Q. Huo et al., “Cooperative formation of inorganic-organic interfaces in the synthesis of silicate mesostructures,” Science, vol. 261, no. 5126, pp. 1299–1303, 1993.
View at: Publisher Site | Google Scholar
L. W. Hench and J. K. West, “The sol-gel process,” Chemical Reviews, vol. 90, no. 1, pp. 33–72, 1990.
View at: Publisher Site | Google Scholar
Y. Lu, H. Fan, A. Stump, T. L. Ward, T. Rieker, and C. J. Brinker, “Aerosol-assisted self-assembly of mesostructured spherical nanoparticles,” Nature, vol. 398, no. 6724, pp. 223–226, 1999.
View at: Publisher Site | Google Scholar
H. Yang, N. Coombs, I. Sokolov, and G. A. Ozin, “Free-standing and oriented mesoporous silica films grown at the air–water interface,” Nature, vol. 381, no. 6583, pp. 589–592, 1996.
View at: Publisher Site | Google Scholar
C. J. Brinker, “Evaporation-induced self-assembly: functional nanostructures made easy,” MRS Bulletin, vol. 29, no. 9, pp. 631–640, 2004.
View at: Publisher Site | Google Scholar
G. J. Soler-Illia, P. C. Angelomé, M. C. Fuertes, D. Grosso, and C. Boissiere, “Critical aspects in the production of periodically ordered mesoporous titania thin films,” Nanoscale, vol. 4, no. 8, pp. 2549–2566, 2012.
View at: Publisher Site | Google Scholar
G. Soler-Illia, C. Sanchez, B. Lebeau, and J. Patarin, “Chemical strategies to design textured materials: from microporous and mesoporous oxides to nanonetworks and hierarchical structures,” Chemical Reviews, vol. 102, no. 11, pp. 4093–4138, 2002.
View at: Publisher Site | Google Scholar
P. Yang, D. Zhao, D. I. Margolese, B. F. Chmelka, and G. D. Stucky, “Generalized syntheses of large-pore mesoporous metal oxides with semicrystalline frameworks,” Nature, vol. 396, no. 6707, pp. 152–155, 1998.
View at: Publisher Site | Google Scholar
H. Luo, C. Wang, and Y. Yan, “Synthesis of mesostructured titania with controlled crystalline framework,” Chemistry of Materials, vol. 15, no. 20, pp. 3841–3846, 2003.
View at: Publisher Site | Google Scholar
X. Fu, L. A. Clark, Q. Yang, and M. A. Anderson, “Enhanced photocatalytic performance of titania-based binary metal oxides: TiO2/SiO2and TiO2/ZrO2,” Science and Technology, vol. 30, no. 2, pp. 647–653, 1996.
View at: Publisher Site | Google Scholar
J. C. Yu, J. Lin, and R. W. M. Kwok, “Ti1-xZrxO2solid solutions for the photocatalytic degradation of acetone in air,” The Journal of Physical Chemistry. B, vol. 102, no. 26, pp. 5094–5098, 1998.
View at: Publisher Site | Google Scholar
J. Marchi, E. M. Amorim, D. R. R. Lazar, V. Ussui, A. H. A. Bressiani, and P. F. Cesar, “Physico-chemical characterization of zirconia–titania composites coated with an apatite layer for dental implants,” Dental Materials, vol. 29, no. 9, pp. 954–962, 2013.
View at: Publisher Site | Google Scholar
H. Tiainen, G. Eder, O. Nilsen, and H. J. Haugen, “Effect of ZrO₂ addition on the mechanical properties of porous TiO₂ bone scaffolds,” Materials Science and Engineering: C, vol. 32, no. 6, pp. 1386–1393, 2012.
View at: Publisher Site | Google Scholar
V. Damodaran, D. Bhatnagar, V. Leszczak, and K. C. Popat, “Titania nanostructures: a biomedical perspective,” RSC Advances, vol. 5, no. 47, pp. 37149–37171, 2015.
View at: Publisher Site | Google Scholar
M. Hamzeh and G. I. Sunahara, “In vitro cytotoxicity and genotoxicity studies of titanium dioxide (TiO₂) nanoparticles in Chinese hamster lung fibroblast cells,” Toxicology in Vitro, vol. 27, no. 2, pp. 864–873, 2013.
View at: Publisher Site | Google Scholar
T. Kokubo, T. Matsushita, and H. Takadama, “Titania-based bioactive materials,” Journal of the European Ceramic Society, vol. 27, no. 2-3, pp. 1553–1558, 2007.
View at: Publisher Site | Google Scholar
R. L. Hentrich, G. A. Graves, H. G. Stein, and P. K. Bajpai, “An evaluation of inert and resorbale ceramics for future clinical orthopedic applications,” Journal of Biomedical Materials Research, vol. 5, no. 1, pp. 25–51, 1971.
View at: Publisher Site | Google Scholar
P. F. Manicone, P. Rossi Iommetti, and L. Raffaelli, “An overview of zirconia ceramics: basic properties and clinical applications,” Journal of Dentistry, vol. 35, no. 11, pp. 819–826, 2007.
View at: Publisher Site | Google Scholar
C. Piconi and G. Maccauro, “Zirconia as a ceramic biomaterial,” Biomaterials, vol. 20, no. 1, pp. 1–25, 1999.
View at: Publisher Site | Google Scholar
T. Thamaraiselvi and S. Rajeswari, “Trends Biomater,” Artificial Organs, vol. 18, 2003.
View at: Google Scholar
K. Houjou, K. Ando, and K. Takahashi, “Crack -Healing Behaviour of Zirconia/SiC Composite Ceramics,” Journal of the Society of Materials Science, Japan, vol. 58, no. 6, pp. 510–515, 2009.
View at: Publisher Site | Google Scholar
K. Houjou, S. Sudo, and K. Takahashi, “Crack-Healing Behaviour of Zirconia /SiC Composite Ceramics and Strength Properties of Crack-Healing Specimens,” Journal of the Society of Materials Science, Japan, vol. 60, no. 8, pp. 742–747, 2011.
View at: Publisher Site | Google Scholar
F. Samanipour, M. R. Bayati, F. Golestani-Fard, H. R. Zargar, T. Troczynski, and A. R. Mirhabibi, “An innovative technique to simply fabricate ZrO₂–HA–TiO₂ nanostructured layers,” Colloids and Surfaces B: Biointerfaces, vol. 86, no. 1, pp. 14–20, 2011.
View at: Publisher Site | Google Scholar
S. M. Mirhadi, N. Hassanzadeh Nemati, F. Tavangarian, and M. Daliri Joupari, “Fabrication of hierarchical meso/macroporous TiO2 scaffolds by evaporation-induced self-assembly technique for bone tissue engineering applications,” Materials Characterization, vol. 144, pp. 35–41, 2018.
View at: Publisher Site | Google Scholar
S. K. Das, M. K. Bhunia, A. K. Sinha, and A. Bhaumik, “Self-assembled mesoporous zirconia and sulfated zirconia nanoparticles synthesized by triblock copolymer as template,” Journal of Physical Chemistry C, vol. 113, no. 20, pp. 8918–8923, 2009.
View at: Publisher Site | Google Scholar
J. Chambers and C. B. Reese, “The thermal decomposition of some polyurethane foams,” British Polymer Journal, vol. 8, no. 2, pp. 48–53, 1976.
View at: Publisher Site | Google Scholar
J. Li, A. Kazakov, and F. L. Dryer, “Experimental and numerical studies of ethanol decomposition reactions,” The Journal of Physical Chemistry A, vol. 108, no. 38, pp. 7671–7680, 2004.
View at: Publisher Site | Google Scholar
P. Moravec, J. Smolík, H. Keskinen, J. Mäkelä, and V. Levdansky, “Vapor Phase Synthesis of Zirconia Fine Particles from Zirconium Tetra-Tert-Butoxide,” Aerosol and Air Quality Research, vol. 7, pp. 563–577, 2007.
View at: Publisher Site | Google Scholar
A. Radtke, P. Piszczek, T. Muziol, A. Wojtczak, and A. Grodzicki, “Synthesis, structural characterization, and thermal properties of zirconium(IV) β-ketodiester complexes,” Structural Chemistry, vol. 21, pp. 367–375, 2009.
View at: Publisher Site | Google Scholar
L. Weng, X. Bao, and K. Sagoe-Crentsil, “Effect of acetylacetone on the preparation of PZT materials in sol–gel processing,” Materials Science and Engineering: B, vol. 96, no. 3, pp. 307–312, 2002.
View at: Publisher Site | Google Scholar
D. Wyrzykowski, E. Hebanowska, G. Nowak-Wiczk, M. Makowski, and L. Chmurzyński, “Thermal behaviour of citric acid and isomeric aconitic acids,” Journal of Thermal Analysis and Calorimetry, vol. 104, no. 2, pp. 731–735, 2011.
View at: Publisher Site | Google Scholar
H. Zhang, C. Tang, Y. Lv et al., “Synthesis, characterization, and catalytic performance of copper-containing SBA-15 in the phenol hydroxylation,” Journal of Colloid and Interface Science, vol. 380, no. 1, pp. 16–24, 2012.
View at: Publisher Site | Google Scholar
J. A. Cecilia, R. Moreno Tost, and M. Retuerto Millán, “Mesoporous materials: from synthesis to applications,” International Journal of Molecular Sciences, vol. 20, no. 13, p. 3213, 2019.
View at: Publisher Site | Google Scholar
D. Hanaor and C. Sorrell, “Review of the anatase to rutile phase transformation,” Journal of Materials Science, vol. 46, no. 4, pp. 855–874, 2011.
View at: Publisher Site | Google Scholar
O. Kurapova and V. G. Konakov, “A Corriger Dans le Texte Aussi Oy Kurapova, and VG Konakov,” Reviews on Advanced Materials Science, vol. 36, pp. 177–190, 2014.
View at: Google Scholar
F. H. Brown Jr. and P. Duwez, “The zirconia-titania system,” Journal of the American Ceramic Society, vol. 37, no. 3, pp. 129–132, 1954.
View at: Publisher Site | Google Scholar
J. Yang and J. M. F. Ferreira, “Inhibitory effect of the Al2O3–SiO2 mixed additives on the anatase–rutile phase transformation,” Materials Letters, vol. 36, no. 5-6, pp. 320–324, 1998.
View at: Publisher Site | Google Scholar
A. Kubiak, K. Siwińska-Ciesielczyk, and T. Jesionowski, “Titania-based hybrid materials with ZnO, ZrO2 and MoS2: a review,” Materials, vol. 11, no. 11, p. 2295, 2018.
View at: Publisher Site | Google Scholar
S. Mascotto, D. Wallacher, A. Brandt et al., “Analysis of microporosity in ordered mesoporous hierarchically structured silica by combining physisorption with in situ small-angle scattering (SAXS and SANS),” Langmuir, vol. 25, no. 21, pp. 12670–12681, 2009.
View at: Publisher Site | Google Scholar
M. Impéror-Clerc, P. Davidson, and A. Davidson, “Existence of a Microporous Corona around the Mesopores of Silica-Based SBA-15 Materials Templated by Triblock Copolymers,” Journal of the American Chemical Society, vol. 122, pp. 11925–11933, 2000.
View at: Google Scholar
S. Fessi, A.-S. Mamede, A. Ghorbel, and A. Rives, “Sol–gel synthesis combined with solid–solid exchange method, a new alternative process to prepare improved Pd/SiO2–Al2O3 catalysts for methane combustion,” Catalysis Communications, vol. 27, pp. 109–113, 2012.
View at: Publisher Site | Google Scholar
T. Hirai, H. Sato, and I. Komasawa, “Mechanism of formation of titanium dioxide ultrafine particles in reverse micelles by hydrolysis of titanium tetrabutoxide,” Industrial and Engineering Chemistry Research, vol. 32, no. 12, pp. 3014–3019, 1993.
View at: Publisher Site | Google Scholar
H. Kumazawa, Y. Hori, and E. Sada, “Synthesis of spherical zirconia fine particles by controlled hydrolysis of zirconium tetrabutoxide in 1-propanol,” The Chemical Engineering Journal, vol. 51, no. 3, pp. 129–133, 1993.
View at: Publisher Site | Google Scholar
S. G. Kumar and K. S. R. K. Rao, “Polymorphic phase transition among the titania crystal structures using a solution-based approach: from precursor chemistry to nucleation process,” Nanoscale, vol. 6, no. 20, pp. 11574–11632, 2014.
View at: Publisher Site | Google Scholar
D. R. Dunphy, P. H. Sheth, F. L. Garcia, and C. J. Brinker, “Enlarged Pore Size in Mesoporous Silica Films Templated by Pluronic F127: Use of Poloxamer Mixtures and Increased Template/SiO₂ Ratios in Materials Synthesized by Evaporation-Induced Self-Assembly,” Chemistry of Materials, vol. 27, pp. 75–84, 2014.
View at: Publisher Site | Google Scholar

Copyright

Copyright © 2020 Shima Mahtabian et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

PDF Download Citation

Download other formats

Order printed copies

Views

1065

Downloads

879

Citations

Journal of Nanomaterials

Applications of Nanobiomaterials in Tissue Repair

Synthesis and Characterization of Hierarchical Mesoporous-Macroporous TiO2-ZrO2 Nanocomposite Scaffolds for Cancellous Bone Tissue Engineering Applications

Abstract

1. Introduction

2. Materials and Methods

2.1. Sample Preparation

2.2. Sample Characterization

3. Results and Discussions

3.1. STA Evaluation

3.2. SEM/EDS Evaluation

3.3. XRD Evaluation

3.4. BET Evaluation

4. Conclusions

Data Availability

Additional Points

Conflicts of Interest

References

Copyright

Synthesis and Characterization of Hierarchical Mesoporous-Macroporous TiO₂-ZrO₂ Nanocomposite Scaffolds for Cancellous Bone Tissue Engineering Applications