Ceramic materials based on lanthanum zirconate for the bone augmentation purposes: materials science approach Chimica Techno Acta LETTER published by Ural Federal University 2022, vol. 9(2), No. 20229209 eISSN 2411-1414; chimicatechnoacta.ru DOI: 10.15826/chimtech.2022.9.2.09 1 of 4 Ceramic materials based on lanthanum zirconate for the bone augmentation purposes: materials science approach Natalia Tarasova * , Anzhelika Galisheva , Ksenia Belova , Anastasia Mushnikova, Elena Volokitina Institute of High Temperature Electrochemistry, Ural Brunch of Russian Academy of Sciences, Ekaterinburg 620137, Russia * Corresponding author: Natalia.Tarasova@urfu.ru This paper belongs to a Regular Issue. © 2022, the Authors. This article is published open access under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). Abstract The creation of new non-toxic materials that combines high osteoin- tegration and strength characteristics is an urgent contemporary challenge. The use of complex oxides, such as lanthanum zirconate (La2Zr2O7), as non-reservable alloplastic implant materials is a novel and promising way of fulfilling this challenge. In this work, the ce- ramic materials based on undoped and alkali-earth (Ca, Sr) doped La2Zr2O7 were obtained. The main physical and chemical characteris- tics of the ceramic materials were determined. The effects of synthe- sis method and dopant nature on the target characteristics of poten- tial allografts were established. Keywords La2Zr2O7 bioceramics augmentation implant osteoreplacement material Received: 12.05.22 Revised: 23.05.22 Accepted: 23.05.22 Available online: 30.05.22 Key findings ● The sol-gel method is more preferable, requiring less time to obtain a single-phase composition. ● The density of the prepared ceramic samples was 3.56–4.16 g/cm3. ● The porosity of the prepared ceramic samples was 30–42%. 1. Introduction A wide range of tasks related to the field of biomedical materials science includes the unresolved problem of ef- fective implant osseointegration [1–8]. Currently known materials which can potentially be used as bone allografts have a number of disadvantages, such as reduced biocom- patibility, allergic and toxic reactions [9–20]. This sug- gests that the creation of new non-toxic materials that combines high osteointegration and strength characteris- tics is an urgent task. The solution of it will provide condi- tions for adequate compensation of bone defects with sub- sequent remodeling of the adjacent bone tissue. As it was shown in the literature, the use of calcium- doped lanthanum zirconate as a non-reservable alloplastic implant is possible and demonstrates positive results in the process of bone remodeling [21]. The choice of this material was due to the fact that the crystal structure of lanthanum zirconate (Figure 1) is tolerant to various sub- stitutions, including calcium and strontium ions. Moreo- ver, it was shown that strontium incorporation into calci- um phosphate ceramics results in improved biocompatibil- ity, osteoconductivity and strength [22]. However, despite promising preliminary results, this approach requires comprehensive development both in terms of traumatolo- gy, physiology, and chemical materials science. To date, the influence of metal nature on the processes of osseoin- tegration remains unclear. In particular, the possibility of ion exchange of augment and bone tissue has not been studied. There are no data on bone remodeling markers in the experiment. The degree of biomechanical correspond- ence of the augment based on lanthanum zirconate and bone tissue has not been established. In the present study, the ceramic materials based on undoped and alkali-earth (Ca, Sr) doped lanthanum zir- conate were successfully obtained. The main physical and chemical characteristics of the prepared ceramic materials were determined, and the effects of the synthesis method and dopant modification on the target characteristics of potential allografts were established. 2. Experimental The complex oxides La2Zr2O7, La0.9Ca0.1Zr2O6.95 and La0.9Sr0.1Zr2O6.95 were obtained by three different ways. The sol-gel synthesis method (Figure 1d) was taken from http://chimicatechnoacta.ru/ https://doi.org/10.15826/chimtech.2022.9.2.09 mailto:Natalia.Tarasova@urfu.ru http://creativecommons.org/licenses/by/4.0/ http://orcid.org/0000-0001-7800-0172 https://orcid.org/0000-0003-4346-5644 https://orcid.org/0000-0003-0768-7039 https://crossmark.crossref.org/dialog/?doi=https://doi.org/10.15826/chimtech.2022.9.2.09&domain=pdf&date_stamp=2022-5-30 Chimica Techno Acta 2022, vol. 9(2), No. 20229209 LETTER 2 of 4 [23]. The solid-state method was performed by mill and using agate mortar (Figure 1c). The powders of initial ma- terials, La2О3, ZrО2, CaCО3, SrCО3, were previously dried, weighed and mixed in stoichiometric quantities. The calci- nation was performed in the temperature range from 800 to 1300 °С with a step of 100 °С and 24 h dwells. The mill- ing of powders was made after each calcination step. The X-ray diffraction (XRD) studies were performed by a Bruker Advance D8 Cu Kα diffractometer with a scan- ning step of 0.01° and at a scanning rate of 0.5°/min. The morphology and chemical composition of the samples were studied using a scanning electron microscope Phe- nom ProX Desktop (SEM) equipped with an energy- dispersive X-ray diffraction (EDS) detector. 3. Results and discussions In the experiment, nine powder samples were obtained. Each La2Zr2O7, La0.9Ca0.1Zr2O6.95 and La0.9Sr0.1Zr2O6.95 com- position was produced by three different methods: sol-gel (SG) method, solid state (SS) method using a mortar for grinding and solid state method using a ball mill. First, the XRD-check for the phase formation process was performed after 1100 °C heat treatment. For the compositions ob- tained by the SG method, all peaks were indexed in the Fd3m space group. However, they were broad, so the in- crease in the sintering temperature was required. After the same synthesis step (1100 °C), the compositions ob- tained by both variations of solid state method were not single phase. The peaks belonging to the metal oxides were detected together with the peaks of the target com- plex oxide phase. The second XRD-check was performed after the next stage of treatment (1200 °C, 24 h). The peak broadening for the SG-compositions were observed. However, they were less pronounced in comparison with the previous stage. The intensity of metal oxide peaks in the XRD-data for the SS-compositions was lower than it was after the previous stage, but all compositions were not single phase yet. The third XRD-check was made after 1300 °C treat- ment for 24 h. The SG-compositions were single-phase, the peaks were not broadened. The SS-compositions ob- tained using the mill were single phase as well. As an ex- ample, Figure 1e presents the photo of the powder sample of La2Zr2O7, and the corresponding XRD-data is shown in Figure 1a. The SS-compositions obtained using the mortar contained both complex oxide and initial reagents. The single-phase compositions were obtained only after 1600 °C treatment for 24 h. It should be noted that doping leads to a slight decrease in the unit cell parameters (10.810 Å for La2Zr2O7, 10.797 Å for La0.9Ca0.1Zr2O6.95, 10.805 Å for La0.9Sr0.1Zr2O6.95). Thus, we can conclude that the presence of alkali-earth dopants in the structure of lanthanum zirconate does not affect the final annealing temperature that is necessary for obtaining a single-phase composition. The use of SG and SS-mill synthesis methods allow single phase compo- sitions at the lower temperatures to be obtained. At the same time, the SG-method is more preferable due to less time it takes to obtain single-phase compositions. Figure 1 The XRD-pattern (a), crystal structure (b), photo of powder sample, image of surface of ceramic sample (f) of composition La2Zr2O7; schemes of solid state (c) and sol-gel (d) synthesis methods; image of ceramic pellets (g) and of bone with augmentation. Chimica Techno Acta 2022, vol. 9(2), No. 20229209 LETTER 3 of 4 Table 1 The density (g/cm3) and porosity (%) of the fabricated ceramic samples. Composition Density Porosity La2Zr2O7 (SG) 4.02 33 La0.9Ca0.1Zr2O6.95 (SG) 3.94 36 La0.9Sr0.1Zr2O6.95 (SG) 4.16 30 La2Zr2O7 (SS-mill) 3.89 35 La0.9Ca0.1Zr2O6.95 (SS-mill) 3.41 42 La0.9Sr0.1Zr2O6.95 (SS-mill) 3.56 40 The morphology of the powder samples was studied using the scanning electron microscopy (SEM). The doping did not significantly affect the dispersity of the samples. The SG-compositions consisted of irregular round-shaped grains with a size of 30−50 μm, forming agglomerates of up to 100 μm. The SS-compositions were represented by the grains with ~3−5 μm, forming agglomerates of ~10–15 μm. The grain boundaries for all samples were clean. The chemical composition and the elements distri- bution were determined by energy-dispersive spectrosco- py (EDS) analysis performed on polished cleavage of the ceramic samples. The ceramic samples were prepared by pressing of cylindrical pellets (pressure ~7 MPa) (Fig- ure 1g) and sintering them at 1400 °C for 24 h. The image of the surface of ceramic La2Zr2O7 sample is shown in Fig- ure 1f. Homogeneous distribution of the elements was ob- served; the concentration of dopant at the grain bounda- ries and in the bulk of the grain was comparable. The relative density and porosity of ceramic samples are presented in Table 1. As we can see, the density of SG- compositions is higher as compared with the density of SS-compositions. The porosity of the SG-compositions is lower; however, it is high enough. It is obvious that to increase the ceramic density, it is necessary either to use sintering additives or to modify the method of synthesis. However, the requirements for bone augmentation ceram- ics (Figure 1h) are different and they depend on many fac- tors including the type and condition of the bone and the size of the implant. 4. Conclusions In this paper, the materials science approach to the prob- lem of obtaining novel ceramic materials for the bone augmentation purposes was implemented. The ceramics based on undoped and alkali-earth (Ca, Sr) doped lantha- num zirconate were obtained by three different methods: sol-gel method, solid state method in the mortar and solid state method in the mill. It was shown that the presence of an alkali-earth dopant in the structure of lanthanum zir- conate does not affect the final annealing temperature required for obtaining single-phase compositions in less time. However, the sol-gel method is more preferable it allows synthesizing a single-phase composition. The densi- ty of ceramic samples obtained using the solid state meth- od (3.56–3.89 g/cm3) was lower in comparison with the samples obtained by the sol-gel method (3.94–4.16 g/cm3). The porosity was lower for the latter. We can conclude that effects of the synthesis method and the presence of a dopant in the structure on the basic properties of ceramic samples were established. However, this work is only a first step to obtaining novel highly effective ceramic mate- rials for the bone augmentation. Supplementary materials No supplementary materials are available. Funding This work was supported by the Russian Science Founda- tion (grant no. 22-25-20037), https://www.rscf.ru/en. Acknowledgments None. Author contributions Conceptualization: N.T. Data curation: A.G., K.B., A.M. Funding acquisition: E.V. Investigation: A.G., K.B. Methodology: N.T. Validation: A.G., K.B., N.T. Visualization: N.T. Writing – original draft: N.T. Writing – review & editing: N.T. Conflict of interest The authors declare no conflict of interest. Additional information Author IDs: Natalia Tarasova, Scopus ID 37047923700; Anzhelika Galisheva, Scopus ID 57195274932; Ksenia Belova, Scopus ID 56509536000. Website: Institute of High Temperature Electrochemistry UB RAS, http://www.ihte.uran.ru/. References 1. Winkler T, Sass FA, Duda GN, Schmidt-Bleek K. A review of biomaterials in bone defect healing, remaining shortcomings https://www.rscf.ru/en https://www.scopus.com/authid/detail.uri?authorId=37047923700 https://www.scopus.com/authid/detail.uri?authorId=57195274932 https://www.scopus.com/authid/detail.uri?authorId=56509536000 http://www.ihte.uran.ru/ Chimica Techno Acta 2022, vol. 9(2), No. 20229209 LETTER 4 of 4 and future opportunities for bone tissue engineering: The un- solved challenge. Bone Joint Res. 2018;7(3):232–243. doi:10.1302/2046-3758.73.BJR-2017-0270.R1 2. Natarajan D, Ye Z, Wang L, Ge L, Pathak JL. Rare earth smart nanomaterials for bone tissue engineering and implantology: Advances, challenges, and prospects. Bioeng Transl Med. 2021;(1):e10262. doi:10.1002/btm2.10262 3. Zhao R, Yang R, Cooper PR, Khurshid Z, Shavandi A, Ratnayake J. Bone grafts and substitutes in dentistry: a re- view of current trends and developments. Mol. 2021;26(10):3007. doi:10.3390/molecules26103007 4. Zhang LY, Bi Q, Zhao C, Chen JY, Cai MH, Chen XY. Recent advances in biomaterials for the treatment of bone defects. Organog. 2020;16(4):113–125. doi:10.1080/15476278.2020.1808428 5. Wang W, Yeung KWK. Bone grafts and biomaterials substi- tutes for bone defect repair: a review. Bioact Mater. 2017;2(4):224–247. doi:10.1016/j.bioactmat.2017.05.007 6. Haugen HJ, Lyngstadaas SP, Rossi P, Perale G, Periodontol JC. Bone grafts: which is the ideal biomaterial? J Clin Periodon- tol. 2019;46(Suppl 21):92–102. doi:10.1111/jcpe.13058 7. Panseri S, Montesi M, Hautcoeur D, Dozio SM, Chamary S, De Barra E, Tampieri A, Leriche A. Bone-like ceramic scaffolds designed with bioinspired porosity induce a different stem cell response. J Mater Sci Mater Med. 2021;32(1):3. doi:10.1007/s10856-020-06486-3 8. Wei H, Cui J, Lin K, Xie J, Wang X. Recent advances in smart stimuli-responsive biomaterials for bone therapeutics and regeneration. Bone Res. 2022;10:17. doi:10.1038/s41413-021-00180-y 9. Wang P, Zhao L, Liu J, Weir MD, Zhou X, Xu HHK. Bone tissue engineering via nanostructured calcium phosphate bio- materials and stem cells. Bone Res. 22015:14017. doi:10.1038/boneres.2014.17 10. Zhang K ,Wang S, Zhou C, Cheng L, Gao X, Xie X, Sun J, Wang H, Weir MD, Reynolds MA, Zhang N, Bai Y. Advanced smart biomaterials and constructs for hard tissue engineering and regeneration. Bone Res. 2018;6(11):31. doi:10.1038/s41413-018-0032-9 11. Khan F, Tanaka M. Designing smart biomaterials for tissue engineering. Int J Molecular Sci. 2018;19:17. doi:10.3390/ijms19010017 12. Oliveira ÉR, Nie L, Podstawczyk D, Allahbakhsh A, Ratnayake J, Brasil DL. Shavandi SA. Advances in growth factor delivery for bone tissue engineering. Int J Molecular Sci. 2021;22:903. doi:10.3390/ijms22020903 13. Sarian MN, Iqbal N, Sotoudehbagha P, Razavi M, Ahmed QU, Sukotjo C, Hermawan H. Potential bioactive coating system for high-performance absorbable magnesium bone implants. Bioact Mater. 2022;22:42–63. doi:10.1016/j.bioactmat.2021.10.034 14. Ressler A, Ivanišević I, Žužić A, Somers N. The ionic substi- tuted octacalcium phosphate for biomedical applications: a new pathway to follow? Ceram Int. 2022;48(7):8838–88511. doi:10.1016/j.ceramint.2021.12.126 15. Zhu G, Zhang T, Chen M, Yao K, Huang X, Zhang B, Li Y, Liu J, Wang Y, Zhao Z. Bone physiological microenvironment and healing mechanism: basis for future bone-tissue engineering scaffolds. Bioact Mater. 2021;6(11):4110–4140. doi:10.1016/j.bioactmat.2021.03.043 16. Matsunaga K, Murata H. Strontium substitution in bioactive calcium phosphates: A first-principles study. J Phys Chem B. 2009;113(11):3584–3589. doi:10.1021/jp808713m 17. Chen Z, Tong J, Li X, Yan Y. Advantages and disadvantages of interbody implant materials in lumbar fusion. Chin J Tissue Eng Res. 2022;26(10):1671–1678. doi:10.12307/2022.209 18. Zhang JA, Lam PH, Beretov J, Murrell GAC. A review of bone grafting techniques for glenoid reconstruction. Shoulder El- bow. 2022;14(2):123–134. doi:10.1177/17585732211008474 19. Rodríguez-Merchán EC. Bone healing materials in the treat- ment of recalcitrant nonunions and bone defects. Int J Molec- ular Sci. 2022;23:3352. doi:10.3390/ijms23063352 20. Dixon DT, Gomillion CT. Conductive scaffolds for bone tissue engineering: current state and future outlook. J Functional Biomater. 2022;13(1):1. doi:10.3390/jfb13010001 21. Izmodenova MYu, Gilev MV, Ananyev MV, Zaytsev DV, An- tropova IP, Farlenkov AS, Tropin ES, Volokitina EA, Kutepov SM, Yushkov BG. Bone tissue properties after lanthanum zir- conate ceramics implantation: experimental study. Trau- matol Orthop Russ. 2020;26(3):130–140. doi:10.21823/2311-2905-2020-26-3-130-140 22. Silva ADR, Pallone EMJA, Lobo AO. Modification of surfaces of alumina-zirconia porous ceramics with Sr2+ after SBF. J Aust Ceram Soc. 2020;56:517–524. doi:10.1007/s41779-019-00360-4 23. Lyagaeva YuG, Medvedev DA, Demin AK, Yaroslavtseva TV, Plaksin SV, Porotnikova NM. Specific features of preparation of dense ceramic based on barium zirconate. Semicond. 2014;48(10);1353–1358. doi:10.1134/S1063782614100182 https://doi.org/10.1302/2046-3758.73.BJR-2017-0270.R1 https://doi.org/10.1002/btm2.10262 https://doi.org/10.3390/molecules26103007 https://doi.org/10.1080/15476278.2020.1808428 https://doi.org/10.1016/j.bioactmat.2017.05.007 https://doi.org/10.1111/jcpe.13058 https://doi.org/10.1007/s10856-020-06486-3 https://doi.org/10.1038/s41413-021-00180-y https://doi.org/10.1038/boneres.2014.17 https://doi.org/10.1038/s41413-018-0032-9 https://doi.org/10.3390/ijms19010017 https://doi.org/10.3390/ijms22020903 https://doi.org/10.1016/j.bioactmat.2021.10.034 https://doi.org/10.1016/j.ceramint.2021.12.126 https://doi.org/10.1016/j.bioactmat.2021.03.043 https://doi.org/%2010.1021/jp808713m https://doi.org/10.12307/2022.209 https://doi.org/10.1177/17585732211008474 https://doi.org/10.3390/ijms23063352 https://doi.org/10.3390/jfb13010001 https://doi.org/10.21823/2311-2905-2020-26-3-130-140 https://doi.org/10.1007/s41779-019-00360-4 https://doi.org/10.1134/S1063782614100182