Strontium-containing nanostructured hydroxyapatite microspheres for bone regeneration
Keywords:Biomaterials; Bone regeneration; Critical bone defect; Hydroxyapatite; Strontium.
The aim of this study was to analyze the biological behavior and osteogenic potential of nanostructured hydroxyapatite microspheres substituted with strontium (nHASr). Therefore, twenty adult male Wistar rats were randomly distributed into two groups: GnHASr – critical bone defect filled with nHASr microspheres; e CG (control group) – critical bone defect without implantation of biomaterial; evaluated at the biological points of 30 and 60 days. The collected specimens were processed and stained with hematoxylin-eosin (HE) and Masson-Goldner trichrome (TG) and examined by light microscopy. Posteriorly, they were analyzed histomorphometrically to measure the percentage of neoformed osteoid matrix (%OM). In both groups studied, at all biological points, deposition of reparative osteoid matrix (OM) was observed near the bone edges; discrete chronic inflammatory response; connective tissue formation and neovascularization in the residual area of the defect. In the GnHASr, in the two evaluated periods, the deposition of OM was also noticed, both around and inside the microspheres. At 60 days, an area of 7.54% of OM deposition in relation to the total defect area was evidenced in the GnHASr, while in the CG this value was 6.80%. It is concluded that the nHASr microspheres evaluated were biocompatible, biodegradable, bioresorbable, bioactive and osteoconductive. In both groups, the formation of neomineralized tissue occurred in a limited way, which indicates that the concentration of metal used in the replacement did not favor greater osteogenic potential for the biomaterial. The evaluated biomaterial it's adequate for use as a filling material.
Aina, V., Bergandi, L., Lusvardi, G., Malavasi, G., Imrie, F. E., Gibson, I. R., Cerrato, G. & Ghigod, D. (2013). Sr-containing hydroxyapatite: morphologies of HA crystals and bioactivity on osteoblast cells. Materials Science and Engineering: C, 33(3), 1132-1142.
Ammann, P., Shen, V., Robin, B., Mauras, Y., Bonjour, J. & Rizzoli, R. (2004). Strontium Ranelate Improves Bone Resistance by Increasing Bone Mass and Improving Architecture in Intact Female Rats. Journal of Bone and Mineral Research, 19(12), 2012-2020.
Anderson, J. M., Rodriguez, A. & Chang, D. T. (2008). Foreign body reaction to biomaterials. Seminars in Immunology, 20(2), 86-100.
Bonnelye, E., Chabadel, A., Saltel, F. & Jurdic, P. (2008). Dual effect of strontium ranelate: Stimulation of osteoblast differentiation and inhibition of osteoclast formation and resorption in vitro. Bone, 42(1),129-138.
Bootchanont, A., Sailuam, W., Sutikulsombat, S., Temprom, L., Chanlek, N., Kidkhunthod, P., Suwanna, P. & Yimnirun, R. (2017). Synchrotron X-ray Absorption Spectroscopy study of local structure in strontium-doped hydroxyapatite. Ceramics International, 43(14), 11023-11027.
Borciani, G., Ciapetti, G., Vitale-Brovarone, C. & Baldini, N (2022). Strontium Functionalization of Biomaterials for Bone Tissue Engineering Purposes: A Biological Point of View. Materials, 15, 1724.
Buchaim, D. V., Andreo, J. C., Pomini, K. T., Barraviera, B., Ferreira Júnior, R. S., Duarte, M. A. H., Alcalde, M. P., Reis, C. H. B., Teixeira, D. B., Bueno, C. R. S., Detregiachi, C. R. P., Araujo, A. C. & Buchaim, R. L. (2022). A biocomplex to repair experimental critical size defects associated with photobiomodulation therapy. Journal of Venomous Animals and Toxins including Tropical Diseases, 28, e20210056.
Cai, Y., Liu, Y., Yan, W., Hu, Q., Tao, J., Zhang, M., Shi, Z. & Tang, R. (2007). Role of hydroxyapatite nanoparticle size in bone cell proliferation. Journal of Materials Chemistry, 17, 3780-3787.
Calasans-Maia, M., Calasans-Maia, J., Santos, S., Mavropoulos, E., Farina, M., Lima, I., Lopes, R. T., Rossi, A. & Granjeiro, J. M. (2014). Short-term in vivo evaluation of zinc-containing calcium phosphate using a normalized procedure. Materials Science and Engineering: C, 41, 309-319.
Carmo, A. B. X., Sartoretto, S. C., Alves, A. T. N. N., Granjeiro, J. M., Miguel, F. B., Calasans-Maia, J. & Calasans-Maia, M. D. (2018). Alveolar bone repair with strontium-containing nanostructured carbonated hydroxyapatite. Journal of Applied Oral Science, 26, e20170084.
Combes, C., Cazalbou, S. & Rey, C. (2016). Apatite Biominerals. Minerals, 6(2), 1-25.
Conz, M. B., Granjeiro, J. M. & Soares, G. A. (2011). Hydroxyapatite crystallinity does not affect the repair of critical size bone defects. Journal of Applied Oral Science, 19(4), 337-42
Costa, N. M, Yassuda, D. H., Sader, M. S., Fernandes, G. V., Soares, G. D., & Granjeiro, J. M. (2016). Osteogenic effect of tricalcium phosphate substituted by magnesium associated with Genderm® membrane in rat calvarial defect model. Materials Science and Engineering C, 61(1), 63-71.
Cuozzo, R. C., Sartoretto, S. C., Resende, R. F. B., Alves, A. T. N. N., Mavropoulos, E., Prado da Silva, M. H. & Calasans-Maia, M. D. (2020). Biological evaluation of zinc-containing calcium alginate-hydroxyapatite composite microspheres for bone regeneration. Journal of Biomedical Materials Research Part B: Applied Biomaterials, 1–11.
Ehret, C., Aid-Launais, R., Sagardoy, T., Siadous, R., Bareille, R., Rey, S., Pechev, S., Etienne, L., Kalisky, J., Mones, E., Letourneur, D., & Amedee Vilamitjana, J. (2017). Strontium-doped hydroxyapatite polysaccharide materials effect on ectopic bone formation. PLOS ONE, 12(9), 1-21.
Harrison, C. J., Hatton, P. V., Gentile, P. & Miller, C. A. (2021). Nanoscale Strontium-Substituted Hydroxyapatite Pastes and Gels for Bone Tissue Regeneration. Nanomaterials, 11(6), 1611.
Jiang, S., Wang, X., Ma, Y., Zhou, Y., Liu, L., Yu, F., Fang, B., Lin, K., Xia, L. & Cai, M. (2022). Synergistic Effect of Micro-Nano-Hybrid Surfaces and Sr Doping on the Osteogenic and Angiogenic Capacity of Hydroxyapatite Bioceramics Scaffolds. International Journal Nanomedicine, 17, 783–797.
Kammer, G. M., Sartoretto, S. C., Resende, R., Uzeda, M., Nascimento, J. R., Alves, A. T., Calasans-Maia, J., Rossi, A. M., Granjeiro, J. M. & Calasans-Maia, M. D. (2016). In vivo evaluation of strontium-containing nanostructured carbonated hydroxyapatite. Key Engineering Materials, 696, 212-222.
Kołodziejska, B., Stepien, N. & Kolmas, J (2021). The Influence of Strontium on Bone Tissue Metabolism and Its Application in Osteoporosis Treatment. International Journal of Molecular Sciences, 22, 6564.
Lala, S., Brahmachari, S., Das, P. K., Das, D., Kar, T. & Pradhan, S. K. (2014). Biocompatible nanocrystalline natural bonelike carbonated hydroxyapatite synthesized by mechanical alloying in a record minimum time. Materials Science and Engineering C, 42, 647–656.
Li, B., Liao, X., Zheng, L., He, H., Wang, H., Fan, H. & Zhang, X. (2012). Preparation and cellular response of porous A-type carbonated hydroxyapatite nanoceramics. Materials Science and Engineering C, 32, 929-936.
Liu, S., Zhou, H., Liu, H., Ji, H., Fei, W. & Luo, E. (2019). Fluorine‐contained hydroxyapatite suppresses bone resorption through inhibiting osteoclasts differentiation and function in vitro and in vivo. Cell Proliferation, 52(3), e12613.
Liu, X., Huang, H., Zhang, J., Sun, T., Zhang, W. & Li, Z. (2023). Recent Advance of Strontium Functionalized in Biomaterials for Bone Regeneration. Bioengineering, 10, 414.
Luo, Y., Chen, S., Shi, Y. & Ma, J. (2018). 3D printing of strontium-doped hydroxyapatite based composite scaffolds for repairing critical-sized rabbit calvarial defects. Biomedical Materials, 13(6), 065004.
Ma, P., Chen, T., Wu, X., Hu, Y., Huang, K., Wang, Y. & Dai, H. (2021). Effects of bioactive strontium-substituted hydroxyapatite on osseointegration of polyethylene terephthalate artificial ligaments. Journal of Materials Chemistry B, 9, 6600-6613.
Machado, C. P. G., Pintor, A. V. B., Gress, M. A. K. A., Rossi, A. M., Granjeiro, J. M & Calasans Maia, M. D. (2010). Avaliação da hidroxiapatita contendo estrôncio como substituto ósseo em tíbias de ovelhas. Innovations Implant Journal: Biomaterials and Esthetics, 5(1), 9-14.
Machado, C. P. G., Sartoretto, S. C., Alves, A. T. N. N., Lima, I. B. C., Rossi, A. M., Granjeiro, J. M. & Calasans-Maia, M. D. (2016). Histomorphometric evaluation of strontium-containing nanostructured hydroxyapatite as bone substitute in sheep. Brazilian Oral Research, 30(1), e45 1-11.
Marx, D., Rahimnejad Yazdi, A., Papini, M. & Towler, M. (2020). A review of the latest insights into the mechanism of action of strontium in bone. Bone Reports, 12, 100273.
Miguel, F. B., Barbosa Júnior, A. A., de Paula, F. L., Barreto, I. C., Goissis, G. & Rosa, F. P. (2013). Regeneration of critical bone defects with anionic collagen matrix as scaffolds. Journal of Materials Science: Materials in Medicine, 24(11), 2567-2575.
Miguel, F.B., Cardoso, A. K. M. V., Barbosa Júnior, A. A., Marcantonio Júnior, E., Goissis, G. & Rosa, F. P. (2006). Morphological assessment of the behavior of three-dimensional anionic collagen matrices in bone regeneration in rats. Journal of Biomedical Materials Research Part B: Applied Biomaterials, 78B(2), 334-339.
Mir, M., Leite, F. L., Herrmann Junior, P. S. P., Pissetti, F. L., Rossi, A. M., Moreira, E. L. & Mascarenhas, Y. P. (2012). XRD, AFM, IR and TGA Study of Nanostructured Hydroxyapatite. Materials Research, 15(4), 622-627.
Petrovic, M., Colovic, B., Jokanovic, V. & Markovic, D. (2012). Self assembly of biomimetic hydroxyapatite on the surface of different polymer thin films. Journal of Ceramic Processing Research, 13(4), 398-404.
Porto, G. G., Vasconcelos, B. C. E., Andrade, E. S. S., Carneiro, S. C. A. S. & Frota, M. S. M. (2012). Is a 5 mm rat calvarium defect really critical? Acta Cirurgica Brasileira, 27(11), 757-760.
Querido, W., Rossi, A. L. & Farina, M. (2016). The effects of strontium on bone mineral: A review on current knowledge and microanalytical approaches. Micron, 80, 122-134.
Ratnayake, J. T. B., Mucalo, M. & Dias, G. J. (2016). Substituted hydroxyapatites for bone regeneration: a review of current trends. Journal of Biomedical Materials Research Part B: Applied Biomaterials, 105, 1285-99.
Ribeiro, I. I. A., Almeida, R. S., Rocha, D. N., Prado da Silva, M., Miguel, F. B. & Rosa, F. P. (2015) Biocerâmicas e polímero para a regeneração de defeitos ósseos críticos. Revista de Ciências Médicas e Biológicas, 13(3), 298-302.
Santos, G. G., Miguel, I. R. J. B., Barbosa Junior, A. A., Barbosa, W. T., Almeida, K. V., García-Carrodeguas, R., Fook, M. L., Rodríguez, M. A., Miguel, F. B., Araújo, R. P. C. & Rosa, F. P. (2021a). Bone regeneration using Wollastonite/β-TCP scaffolds implants in critical bone defect in rat calvaria. Biomedical Physics & Engineering Express, 7, 055015, 1-17.
Santos, G. G., Nunes, V. L. C., Marinho, S. M. O. C., Santos, S. R. A., Rossi, A. M. & Miguel, F. B. (2021b). Biological behavior of magnesium-substituted hydroxyapatite during bone repair. Brazilian Journal of Biology, 81(1), 53-61.
Santos, G. G., Vasconcelos, L. Q., Poy, S. C. S., Almeida, R. S., Barbosa Júnior, A. A., Santos, S. R. A., Rossi, A. M., Miguel, F. B. & Rosa, F. P. (2019). Influence of the geometry of nanostructured hydroxyapatite and alginate composites in the initial phase of bone repair. Acta Cirúrgica Brasileira, 34(2), e201900203
Schmitz, J. P. & Hollinger, J. O. (1986). The critical size defect as an experimental model for craniomandibulofacial nonunions. Clinical Orthopaedics and Related Research, (205), 299-308.
Scudeller, L. A., Mavropoulos, E., Tanaka, M. N., Costa, A. M., Braga, C. A. C., López, E. O., Mello, A. & Rossi, A. M. (2017). Effects on insulin adsorption due to zinc and strontium substitution in hydroxyapatite. Materials Science and Engineering C, 79, 802-811.
Shepherd, J. H., Shepherd, D. V. & Best, S. M. (2012). Substituted hydroxyapatites for bone repair. Journal of Materials Science: Materials in Medicine, 23(10), 2335-2347.
Spicer, P., Kretlow, J., Young, S., Jansen, J. A., Kasper, F. K. & Mikos, A. G. (2012). Evaluation of bone regeneration using the rat critical size calvarial defect. Nature Protocols, 7(10), 1918-1929.
Su, X., Sun, K., Cui, F. Z. & Landis, W. J. (2003). Organization of apatite crystals in human woven bone. Bone, 32, 150-162.
Tite, T., Popa, A. C., Balescu, L. M., Bogdan, I. M., Pasuk, I., Ferreira, J. M. F. & Stan, G. E. (2018). Cationic Substitutions in Hydroxyapatite: Current Status of the Derived Biofunctional Effects and Their In Vitro Interrogation Methods. Materials, 11(11), 2081.
Valenzuela, F., Covarrubias, C., Martínez, C., Smith, P., Díaz-Dosque, M. & Yazdani-Pedram, M. (2012). Preparation and bioactive properties of novel bone-repair bionanocomposites based on hydroxyapatite and bioactive glass nanoparticles. Journal of Biomedical Materials Research Part B: Applied Biomaterials, 100B(6), 1672-1682.
Valiense, H., Barreto, M., Resende, R. F., Alves, A. T., Rossi, A. M., Mavropoulos, E., Granjeiro, J. M. & Calasans-Maia, M. D. (2015). In vitro and in vivo evaluation of strontium-containing nanostructured carbonated hydroxyapatite/sodium alginate for sinus lift in rabbits. Journal of biomedical materials research. Part B, Applied biomaterials, 104(2), 274-282.
Wang, P., Zhao, L., Liu, J., Weir, M. D., Zhou, X. & Xu, H. H. K. (2014). Bone tissue engineering via nanostructured calcium phosphate biomaterials and stem cells. Bone Research, 2, 14017.
Winkler, T., Sass, F. A., Duda, G. N. & Schmidt-Bleek, K. (2018). A review of biomaterials in bone defect healing, remaining short comings and future opportunities for bone tissue engineering. Bone and joint research, 7(3), 232-243.
Yatongchai, C., Placek, L. M., Towler, M. R. & Wren, A. W. (2015). Effects of Strontium Substitution on Bioactivity of Hydroxyapatite. 41st Annual Northeast Biomedical Engineering Conference (NEBEC), 1-2.
You, J., Zhang, Y. & Zhou, Y. (2022). Strontium Functionalized in Biomaterials for Bone Tissue Engineering: A Prominent Role in Osteoimmunomodulation. Frontiers in Bioengineering and Biotechnology, 10, 1-22.
How to Cite
Copyright (c) 2023 Iorrana Índira dos Anjos Ribeiro; Aryon de Almeida Barbosa Junior; Alexandre Malta Rossi; Renata dos Santos Almeida; Fúlvio Borges Miguel; Fabiana Paim Rosa
This work is licensed under a Creative Commons Attribution 4.0 International License.
Authors who publish with this journal agree to the following terms:
1) Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
2) Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
3) Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work.