In vitro and in vivo evaluations of nanocrystalline Zn-doped carbonated hydroxyapatite/alginate microspheres: zinc and calcium bioavailability and bone regeneration
Victor R Martinez-Zelaya,1 Laila Zarranz,2 Edher Z Herrera,1 Adriana T Alves,2 Marcelo José Uzeda,2 Elena Mavropoulos,1 André L Rossi,1 Alexandre Mello,1 José M Granjeiro,2,3 Monica D Calasans-Maia,2 Alexandre M Rossi11Department of Condensed Matter, Applied Physics...
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2019-05-01
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| Series: | International Journal of Nanomedicine |
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| Online Access: | https://www.dovepress.com/in-vitro-and-in-vivo-evaluations-of-nanocrystalline-zn-doped-carbonate-peer-reviewed-article-IJN |
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| author | Martinez-Zelaya VR Zarranz L Herrera EZ Alves AT Uzeda MJ Mavropoulos E Rossi AL Mello A Granjeiro JM Calasans-Maia MD Rossi AM |
| author_facet | Martinez-Zelaya VR Zarranz L Herrera EZ Alves AT Uzeda MJ Mavropoulos E Rossi AL Mello A Granjeiro JM Calasans-Maia MD Rossi AM |
| author_sort | Martinez-Zelaya VR |
| collection | DOAJ |
| description | Victor R Martinez-Zelaya,1 Laila Zarranz,2 Edher Z Herrera,1 Adriana T Alves,2 Marcelo José Uzeda,2 Elena Mavropoulos,1 André L Rossi,1 Alexandre Mello,1 José M Granjeiro,2,3 Monica D Calasans-Maia,2 Alexandre M Rossi11Department of Condensed Matter, Applied Physics and Nanoscience, Brazilian Center for Research in Physics, Rio de Janeiro, RJ, Brazil; 2Dental Clinical Research Center, Oral Diagnosis Department and Oral Surgery Department, Dentistry School, Fluminense Federal University, Niteroi, RJ, Brazil; 3National Institute of Metrology, Quality and Technology, Duque de Caxias, RJ, BrazilBackground: Zinc-doped hydroxyapatite has been proposed as a graft biomaterial for bone regeneration. However, the effect of zinc on osteoconductivity is still controversial, since the release and resorption of calcium, phosphorus, and zinc in graft-implanted defects have rarely been studied.Methods: Microspheres containing alginate and either non-doped carbonated hydroxyapatite (cHA) or nanocrystalline 3.2 wt% zinc-doped cHA (Zn-cHA) were implanted in critical-sized calvarial defects in Wistar rats for 1, 3, and 6 months. Histological and histomorphometric analyses were performed to evaluate the volume density of newly formed bone, residual biomaterial, and connective tissue formation. Biomaterial degradation was characterized by transmission electron microscopy (TEM) and synchrotron radiation-based X-ray microfluorescence (SR-μXRF), which enabled the elemental mapping of calcium, phosphorus, and zinc on the microsphere-implanted defects at 6 months post-implantation.Results: The bone repair was limited to regions close to the preexistent bone, whereas connective tissue occupied the major part of the defect. Moreover, no significant difference in the amount of new bone formed was found between the two microsphere groups. TEM analysis revealed the degradation of the outer microsphere surface with detachment of the nanoparticle aggregates. According to SR-μXRF, both types of microspheres released high amounts of calcium, phosphorus, and zinc, distributed throughout the defective region. The cHA microsphere surface strongly adsorbed the zinc from organic constituents of the biological fluid, and phosphorus was resorbed more quickly than calcium. In the Zn-cHA group, zinc and calcium had similar release profiles, indicating a stoichiometric dissolution of these elements and non-preferential zinc resorption.Conclusions: The nanometric size of cHA and Zn-cHA was a decisive factor in accelerating the in vivo availability of calcium and zinc. The high calcium and zinc accumulation in the defect, which was not cleared by the biological medium, played a critical role in inhibiting osteoconduction and thus impairing bone repair.Keywords: zinc-doped carbonated hydroxyapatite, nanocomposite, synchrotron radiation-based X-ray microfluorescence, zinc/calcium bioavailability, bone regeneration |
| first_indexed | 2024-12-14T12:49:07Z |
| format | Article |
| id | doaj.art-a192181b08db404f8117b24090edf8fd |
| institution | Directory Open Access Journal |
| issn | 1178-2013 |
| language | English |
| last_indexed | 2024-12-14T12:49:07Z |
| publishDate | 2019-05-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | International Journal of Nanomedicine |
| spelling | doaj.art-a192181b08db404f8117b24090edf8fd2022-12-21T23:00:43ZengDove Medical PressInternational Journal of Nanomedicine1178-20132019-05-01Volume 143471349045739In vitro and in vivo evaluations of nanocrystalline Zn-doped carbonated hydroxyapatite/alginate microspheres: zinc and calcium bioavailability and bone regenerationMartinez-Zelaya VRZarranz LHerrera EZAlves ATUzeda MJMavropoulos ERossi ALMello AGranjeiro JMCalasans-Maia MDRossi AMVictor R Martinez-Zelaya,1 Laila Zarranz,2 Edher Z Herrera,1 Adriana T Alves,2 Marcelo José Uzeda,2 Elena Mavropoulos,1 André L Rossi,1 Alexandre Mello,1 José M Granjeiro,2,3 Monica D Calasans-Maia,2 Alexandre M Rossi11Department of Condensed Matter, Applied Physics and Nanoscience, Brazilian Center for Research in Physics, Rio de Janeiro, RJ, Brazil; 2Dental Clinical Research Center, Oral Diagnosis Department and Oral Surgery Department, Dentistry School, Fluminense Federal University, Niteroi, RJ, Brazil; 3National Institute of Metrology, Quality and Technology, Duque de Caxias, RJ, BrazilBackground: Zinc-doped hydroxyapatite has been proposed as a graft biomaterial for bone regeneration. However, the effect of zinc on osteoconductivity is still controversial, since the release and resorption of calcium, phosphorus, and zinc in graft-implanted defects have rarely been studied.Methods: Microspheres containing alginate and either non-doped carbonated hydroxyapatite (cHA) or nanocrystalline 3.2 wt% zinc-doped cHA (Zn-cHA) were implanted in critical-sized calvarial defects in Wistar rats for 1, 3, and 6 months. Histological and histomorphometric analyses were performed to evaluate the volume density of newly formed bone, residual biomaterial, and connective tissue formation. Biomaterial degradation was characterized by transmission electron microscopy (TEM) and synchrotron radiation-based X-ray microfluorescence (SR-μXRF), which enabled the elemental mapping of calcium, phosphorus, and zinc on the microsphere-implanted defects at 6 months post-implantation.Results: The bone repair was limited to regions close to the preexistent bone, whereas connective tissue occupied the major part of the defect. Moreover, no significant difference in the amount of new bone formed was found between the two microsphere groups. TEM analysis revealed the degradation of the outer microsphere surface with detachment of the nanoparticle aggregates. According to SR-μXRF, both types of microspheres released high amounts of calcium, phosphorus, and zinc, distributed throughout the defective region. The cHA microsphere surface strongly adsorbed the zinc from organic constituents of the biological fluid, and phosphorus was resorbed more quickly than calcium. In the Zn-cHA group, zinc and calcium had similar release profiles, indicating a stoichiometric dissolution of these elements and non-preferential zinc resorption.Conclusions: The nanometric size of cHA and Zn-cHA was a decisive factor in accelerating the in vivo availability of calcium and zinc. The high calcium and zinc accumulation in the defect, which was not cleared by the biological medium, played a critical role in inhibiting osteoconduction and thus impairing bone repair.Keywords: zinc-doped carbonated hydroxyapatite, nanocomposite, synchrotron radiation-based X-ray microfluorescence, zinc/calcium bioavailability, bone regenerationhttps://www.dovepress.com/in-vitro-and-in-vivo-evaluations-of-nanocrystalline-zn-doped-carbonate-peer-reviewed-article-IJNZinc-doped carbonated hydroxyapatitenanocompositeSynchrotron radiation-based X-ray microfluorescenceZinc/Calcium bioavailabilityBone regeneration |
| spellingShingle | Martinez-Zelaya VR Zarranz L Herrera EZ Alves AT Uzeda MJ Mavropoulos E Rossi AL Mello A Granjeiro JM Calasans-Maia MD Rossi AM In vitro and in vivo evaluations of nanocrystalline Zn-doped carbonated hydroxyapatite/alginate microspheres: zinc and calcium bioavailability and bone regeneration International Journal of Nanomedicine Zinc-doped carbonated hydroxyapatite nanocomposite Synchrotron radiation-based X-ray microfluorescence Zinc/Calcium bioavailability Bone regeneration |
| title | In vitro and in vivo evaluations of nanocrystalline Zn-doped carbonated hydroxyapatite/alginate microspheres: zinc and calcium bioavailability and bone regeneration |
| title_full | In vitro and in vivo evaluations of nanocrystalline Zn-doped carbonated hydroxyapatite/alginate microspheres: zinc and calcium bioavailability and bone regeneration |
| title_fullStr | In vitro and in vivo evaluations of nanocrystalline Zn-doped carbonated hydroxyapatite/alginate microspheres: zinc and calcium bioavailability and bone regeneration |
| title_full_unstemmed | In vitro and in vivo evaluations of nanocrystalline Zn-doped carbonated hydroxyapatite/alginate microspheres: zinc and calcium bioavailability and bone regeneration |
| title_short | In vitro and in vivo evaluations of nanocrystalline Zn-doped carbonated hydroxyapatite/alginate microspheres: zinc and calcium bioavailability and bone regeneration |
| title_sort | in vitro and in vivo evaluations of nanocrystalline zn doped carbonated hydroxyapatite alginate microspheres zinc and calcium bioavailability and bone regeneration |
| topic | Zinc-doped carbonated hydroxyapatite nanocomposite Synchrotron radiation-based X-ray microfluorescence Zinc/Calcium bioavailability Bone regeneration |
| url | https://www.dovepress.com/in-vitro-and-in-vivo-evaluations-of-nanocrystalline-zn-doped-carbonate-peer-reviewed-article-IJN |
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