TY  - JOUR
AU  - Lazarević, Miloš M.
AU  - Ignjatović, Nenad
AU  - Mahlet, Qene
AU  - Bumah, Violet V.
AU  - Radunović, Milena
AU  - Milašin, Jelena
AU  - Uskoković, Dragan
AU  - Uskoković, Vuk
PY  - 2024
UR  - https://dais.sanu.ac.rs/123456789/16513
AB  - Hydroxyapatite (HAp) has been the main protagonist in the quest for an ideal biomaterial for regenerative medicine over the last half a century. To control its properties, this material has commonly been doped with chemical elements other than its natural stoichiometric constituents: Ca, O, P, and H. Here, we report on the first analysis of the biological response to germanium-doped hydroxyapatite (Ge-HAp). Cytotoxicity, osteogenic differentiation induction, and colony formation potential were measured on dental pulp stem cells, while the antimicrobial effect was assessed against Gram-negative Escherichia coli, Gram-positive methicillin-resistant Staphylococcus aureus (MRSA), and Candida albicans. All analyses were run in comparison to Ge-free HAp. Cell viability was inversely dependent on the nanoparticle concentration and incubation time. Adding Ge to HAp reduced cell viability relative to HAp after 24–72 h incubation periods, but the effect was reversed after longer incubations, when the viability of cells treated with low doses of Ge-HAp exceeded that of HAp-treated cells and became comparable with control culture. Both HAp and Ge-HAp induced mineral formation in the cell culture, but the effect was more pronounced for Ge-HAp. Likewise, relative to both control cells and cells exposed to HAp, Ge-HAp upregulated the expression of all three osteogenic markers analyzed, namely, alkaline phosphatase, RUNX2, and osteocalcin, exerting the key influence on osteogenesis in its early, differentiation stage. The colony formation capacity of stem cells, however, was impaired by HAp and even more so by Ge-HAp. The antimicrobial effect was dependent on the microorganisms tested. Thus, whereas the antimicrobial activity was absent against E. coli, it was evident against MRSA and C. albicans. While the antibacterial activity against MRSA was weakened by the addition of Ge to HAp, the antimycotic activity against C. albicans was intensified with the addition of Ge. These findings demonstrate a significant potential of Ge-doped HAp nanoparticles in regenerative medicine due to their pronounced biocompatibility, osteoinductivity, and antimicrobial activity.
PB  - American Chemical Society (ACS)
T2  - ACS Applied Nano Materials
T1  - Biocompatible Germanium-Doped Hydroxyapatite Nanoparticles for Promoting Osteogenic Differentiation and Antimicrobial Activity
DO  - 10.1021/acsanm.3c05974
UR  - https://hdl.handle.net/21.15107/rcub_dais_16513
ER  - 

@article{
author = "Lazarević, Miloš M. and Ignjatović, Nenad and Mahlet, Qene and Bumah, Violet V. and Radunović, Milena and Milašin, Jelena and Uskoković, Dragan and Uskoković, Vuk",
year = "2024",
abstract = "Hydroxyapatite (HAp) has been the main protagonist in the quest for an ideal biomaterial for regenerative medicine over the last half a century. To control its properties, this material has commonly been doped with chemical elements other than its natural stoichiometric constituents: Ca, O, P, and H. Here, we report on the first analysis of the biological response to germanium-doped hydroxyapatite (Ge-HAp). Cytotoxicity, osteogenic differentiation induction, and colony formation potential were measured on dental pulp stem cells, while the antimicrobial effect was assessed against Gram-negative Escherichia coli, Gram-positive methicillin-resistant Staphylococcus aureus (MRSA), and Candida albicans. All analyses were run in comparison to Ge-free HAp. Cell viability was inversely dependent on the nanoparticle concentration and incubation time. Adding Ge to HAp reduced cell viability relative to HAp after 24–72 h incubation periods, but the effect was reversed after longer incubations, when the viability of cells treated with low doses of Ge-HAp exceeded that of HAp-treated cells and became comparable with control culture. Both HAp and Ge-HAp induced mineral formation in the cell culture, but the effect was more pronounced for Ge-HAp. Likewise, relative to both control cells and cells exposed to HAp, Ge-HAp upregulated the expression of all three osteogenic markers analyzed, namely, alkaline phosphatase, RUNX2, and osteocalcin, exerting the key influence on osteogenesis in its early, differentiation stage. The colony formation capacity of stem cells, however, was impaired by HAp and even more so by Ge-HAp. The antimicrobial effect was dependent on the microorganisms tested. Thus, whereas the antimicrobial activity was absent against E. coli, it was evident against MRSA and C. albicans. While the antibacterial activity against MRSA was weakened by the addition of Ge to HAp, the antimycotic activity against C. albicans was intensified with the addition of Ge. These findings demonstrate a significant potential of Ge-doped HAp nanoparticles in regenerative medicine due to their pronounced biocompatibility, osteoinductivity, and antimicrobial activity.",
publisher = "American Chemical Society (ACS)",
journal = "ACS Applied Nano Materials",
title = "Biocompatible Germanium-Doped Hydroxyapatite Nanoparticles for Promoting Osteogenic Differentiation and Antimicrobial Activity",
doi = "10.1021/acsanm.3c05974",
url = "https://hdl.handle.net/21.15107/rcub_dais_16513"
}

Lazarević, M. M., Ignjatović, N., Mahlet, Q., Bumah, V. V., Radunović, M., Milašin, J., Uskoković, D.,& Uskoković, V.. (2024). Biocompatible Germanium-Doped Hydroxyapatite Nanoparticles for Promoting Osteogenic Differentiation and Antimicrobial Activity. in ACS Applied Nano Materials
American Chemical Society (ACS)..
https://doi.org/10.1021/acsanm.3c05974
https://hdl.handle.net/21.15107/rcub_dais_16513

Lazarević MM, Ignjatović N, Mahlet Q, Bumah VV, Radunović M, Milašin J, Uskoković D, Uskoković V. Biocompatible Germanium-Doped Hydroxyapatite Nanoparticles for Promoting Osteogenic Differentiation and Antimicrobial Activity. in ACS Applied Nano Materials. 2024;.
doi:10.1021/acsanm.3c05974
https://hdl.handle.net/21.15107/rcub_dais_16513 .

Lazarević, Miloš M., Ignjatović, Nenad, Mahlet, Qene, Bumah, Violet V., Radunović, Milena, Milašin, Jelena, Uskoković, Dragan, Uskoković, Vuk, "Biocompatible Germanium-Doped Hydroxyapatite Nanoparticles for Promoting Osteogenic Differentiation and Antimicrobial Activity" in ACS Applied Nano Materials (2024),
https://doi.org/10.1021/acsanm.3c05974 .,
https://hdl.handle.net/21.15107/rcub_dais_16513 .

TY  - CONF
AU  - Lazarević, Miloš M.
AU  - Ignjatović, Nenad
AU  - Uskoković, Dragan
AU  - Uskoković, Vuk
PY  - 2023
UR  - https://dais.sanu.ac.rs/123456789/15765
AB  - Most of the applications for various forms of ion-doped hydroxyapatite have been geared towards pharmacy, dentistry and medicine. This study presents the first biological, response to germanium-doped hydroxyapatite (Ge-HAp). Viability, osteogenic differentiation induction and colony formation potential of dental pulp stem cells (DPSCs) in the presence of Ge-HAp and pure, Ge-free HAp nanoparticles was assessed. DPSCs were isolated from semiimpacted wisdom teeth extracted from systemically sound patients. MTT was used to determine cell viability after 1, 3, and 7 days of incubation. The effect of Ge-HAp on the expression level of osteodifferentiation markers (RUNX2, ALP, and OCN) was determined using RT-qPCR, and mineralized nodule formation was confirmed using Alizarin Red S staining. The colony-forming unit assay was utilized to evaluate the colony-formation potential of the DPSC. Low dosages of Ge-HAp increased cell viability compared to HAp after a week. Ge-HAp increased cell culture mineralization more than HAp. Ge-HAp substantially upregulated all three osteogenic markers relative to control and Ge-free HApexposed cells. HAp and especially Ge-HAp hindered stem cell colony formation. As demonstrated above, Ge-doped HAp nanoparticles have great promise in regenerative medicine due to their biocompatibility and osteoinductivity.
PB  - Belgrade : Serbian Ceramic Society
C3  - Program and the Book of abstracts / Serbian Ceramic Society Conference Advanced Ceramics and Application XI New Frontiers in Multifunctional Material Science and Processing, Serbian Academy of Sciences and Art Serbia, Belgrade,18-20.September 2023
T1  - The osteogenic effect of Germanium-doped hydroxyapatite nanoparticles on dental pulp stem cells
SP  - 67
EP  - 67
UR  - https://hdl.handle.net/21.15107/rcub_dais_15765
ER  - 

@conference{
author = "Lazarević, Miloš M. and Ignjatović, Nenad and Uskoković, Dragan and Uskoković, Vuk",
year = "2023",
abstract = "Most of the applications for various forms of ion-doped hydroxyapatite have been geared towards pharmacy, dentistry and medicine. This study presents the first biological, response to germanium-doped hydroxyapatite (Ge-HAp). Viability, osteogenic differentiation induction and colony formation potential of dental pulp stem cells (DPSCs) in the presence of Ge-HAp and pure, Ge-free HAp nanoparticles was assessed. DPSCs were isolated from semiimpacted wisdom teeth extracted from systemically sound patients. MTT was used to determine cell viability after 1, 3, and 7 days of incubation. The effect of Ge-HAp on the expression level of osteodifferentiation markers (RUNX2, ALP, and OCN) was determined using RT-qPCR, and mineralized nodule formation was confirmed using Alizarin Red S staining. The colony-forming unit assay was utilized to evaluate the colony-formation potential of the DPSC. Low dosages of Ge-HAp increased cell viability compared to HAp after a week. Ge-HAp increased cell culture mineralization more than HAp. Ge-HAp substantially upregulated all three osteogenic markers relative to control and Ge-free HApexposed cells. HAp and especially Ge-HAp hindered stem cell colony formation. As demonstrated above, Ge-doped HAp nanoparticles have great promise in regenerative medicine due to their biocompatibility and osteoinductivity.",
publisher = "Belgrade : Serbian Ceramic Society",
journal = "Program and the Book of abstracts / Serbian Ceramic Society Conference Advanced Ceramics and Application XI New Frontiers in Multifunctional Material Science and Processing, Serbian Academy of Sciences and Art Serbia, Belgrade,18-20.September 2023",
title = "The osteogenic effect of Germanium-doped hydroxyapatite nanoparticles on dental pulp stem cells",
pages = "67-67",
url = "https://hdl.handle.net/21.15107/rcub_dais_15765"
}

Lazarević, M. M., Ignjatović, N., Uskoković, D.,& Uskoković, V.. (2023). The osteogenic effect of Germanium-doped hydroxyapatite nanoparticles on dental pulp stem cells. in Program and the Book of abstracts / Serbian Ceramic Society Conference Advanced Ceramics and Application XI New Frontiers in Multifunctional Material Science and Processing, Serbian Academy of Sciences and Art Serbia, Belgrade,18-20.September 2023
Belgrade : Serbian Ceramic Society., 67-67.
https://hdl.handle.net/21.15107/rcub_dais_15765

Lazarević MM, Ignjatović N, Uskoković D, Uskoković V. The osteogenic effect of Germanium-doped hydroxyapatite nanoparticles on dental pulp stem cells. in Program and the Book of abstracts / Serbian Ceramic Society Conference Advanced Ceramics and Application XI New Frontiers in Multifunctional Material Science and Processing, Serbian Academy of Sciences and Art Serbia, Belgrade,18-20.September 2023. 2023;:67-67.
https://hdl.handle.net/21.15107/rcub_dais_15765 .

Lazarević, Miloš M., Ignjatović, Nenad, Uskoković, Dragan, Uskoković, Vuk, "The osteogenic effect of Germanium-doped hydroxyapatite nanoparticles on dental pulp stem cells" in Program and the Book of abstracts / Serbian Ceramic Society Conference Advanced Ceramics and Application XI New Frontiers in Multifunctional Material Science and Processing, Serbian Academy of Sciences and Art Serbia, Belgrade,18-20.September 2023 (2023):67-67,
https://hdl.handle.net/21.15107/rcub_dais_15765 .

TY  - JOUR
AU  - Ignjatović, Nenad
AU  - Mančić, Lidija
AU  - Vuković, Marina
AU  - Stojanović, Zoran S.
AU  - Nikolić, Marko G.
AU  - Škapin, Srečo Davor
AU  - Jovanović, Sonja
AU  - Veselinović, Ljiljana
AU  - Uskoković, Vuk
AU  - Lazić, Snežana
AU  - Marković, Smilja
AU  - Lazarević, Miloš M.
AU  - Uskoković, Dragan
PY  - 2019
UR  - https://www.nature.com/articles/s41598-019-52885-0
UR  - https://dais.sanu.ac.rs/123456789/6950
AB  - Taking advantage of the flexibility of the apatite structure, nano- and micro-particles of hydroxyapatite (HAp) were doped with different combinations of rare earth ions (RE3+ = Gd, Eu, Yb, Tm) to achieve a synergy among their magnetic and optical properties and to enable their application in preventive medicine, particularly diagnostics based on multimodal imaging. All powders were synthesized through hydrothermal processing at T ≤ 200 °C. An X-ray powder diffraction analysis showed that all powders crystallized in P63/m space group of the hexagonal crystal structure. The refined unit-cell parameters reflected a decrease in the unit cell volume as a result of the partial substitution of Ca2+ with smaller RE3+ ions at both cation positions. The FTIR analysis additionally suggested that a synergy may exist solely in the triply doped system, where the lattice symmetry and vibration modes become more coherent than in the singly or doubly doped systems. HAp:RE3+ optical characterization revealed a change in the energy band gap and the appearance of a weak blue luminescence (λex = 370 nm) due to an increased concentration of defects. The “up”- and the “down”-conversion spectra of HAp:Gd/Yb/Tm and HAp:Gd/Eu powders showed characteristic transitions of Tm3+ and Eu3+, respectively. Furthermore, in contrast to diamagnetic HAp, all HAp:RE3+ powders exhibited paramagnetic behavior. Cell viability tests of HAp:Gd/Yb/Tm and HAp:Gd/Eu powders in human dental pulp stem cell cultures indicated their good biocompatibility.
PB  - Springer Nature
T2  - Scientific Reports
T1  - Rare-earth (Gd 3+ ,Yb 3+ /Tm 3+ , Eu 3+ ) co-doped hydroxyapatite as magnetic, up-conversion and down-conversion materials for multimodal imaging
SP  - 1
EP  - 15
VL  - 9
IS  - 1
DO  - 10.1038/s41598-019-52885-0
UR  - https://hdl.handle.net/21.15107/rcub_dais_6950
ER  - 

@article{
author = "Ignjatović, Nenad and Mančić, Lidija and Vuković, Marina and Stojanović, Zoran S. and Nikolić, Marko G. and Škapin, Srečo Davor and Jovanović, Sonja and Veselinović, Ljiljana and Uskoković, Vuk and Lazić, Snežana and Marković, Smilja and Lazarević, Miloš M. and Uskoković, Dragan",
year = "2019",
abstract = "Taking advantage of the flexibility of the apatite structure, nano- and micro-particles of hydroxyapatite (HAp) were doped with different combinations of rare earth ions (RE3+ = Gd, Eu, Yb, Tm) to achieve a synergy among their magnetic and optical properties and to enable their application in preventive medicine, particularly diagnostics based on multimodal imaging. All powders were synthesized through hydrothermal processing at T ≤ 200 °C. An X-ray powder diffraction analysis showed that all powders crystallized in P63/m space group of the hexagonal crystal structure. The refined unit-cell parameters reflected a decrease in the unit cell volume as a result of the partial substitution of Ca2+ with smaller RE3+ ions at both cation positions. The FTIR analysis additionally suggested that a synergy may exist solely in the triply doped system, where the lattice symmetry and vibration modes become more coherent than in the singly or doubly doped systems. HAp:RE3+ optical characterization revealed a change in the energy band gap and the appearance of a weak blue luminescence (λex = 370 nm) due to an increased concentration of defects. The “up”- and the “down”-conversion spectra of HAp:Gd/Yb/Tm and HAp:Gd/Eu powders showed characteristic transitions of Tm3+ and Eu3+, respectively. Furthermore, in contrast to diamagnetic HAp, all HAp:RE3+ powders exhibited paramagnetic behavior. Cell viability tests of HAp:Gd/Yb/Tm and HAp:Gd/Eu powders in human dental pulp stem cell cultures indicated their good biocompatibility.",
publisher = "Springer Nature",
journal = "Scientific Reports",
title = "Rare-earth (Gd 3+ ,Yb 3+ /Tm 3+ , Eu 3+ ) co-doped hydroxyapatite as magnetic, up-conversion and down-conversion materials for multimodal imaging",
pages = "1-15",
volume = "9",
number = "1",
doi = "10.1038/s41598-019-52885-0",
url = "https://hdl.handle.net/21.15107/rcub_dais_6950"
}

Ignjatović, N., Mančić, L., Vuković, M., Stojanović, Z. S., Nikolić, M. G., Škapin, S. D., Jovanović, S., Veselinović, L., Uskoković, V., Lazić, S., Marković, S., Lazarević, M. M.,& Uskoković, D.. (2019). Rare-earth (Gd 3+ ,Yb 3+ /Tm 3+ , Eu 3+ ) co-doped hydroxyapatite as magnetic, up-conversion and down-conversion materials for multimodal imaging. in Scientific Reports
Springer Nature., 9(1), 1-15.
https://doi.org/10.1038/s41598-019-52885-0
https://hdl.handle.net/21.15107/rcub_dais_6950

Ignjatović N, Mančić L, Vuković M, Stojanović ZS, Nikolić MG, Škapin SD, Jovanović S, Veselinović L, Uskoković V, Lazić S, Marković S, Lazarević MM, Uskoković D. Rare-earth (Gd 3+ ,Yb 3+ /Tm 3+ , Eu 3+ ) co-doped hydroxyapatite as magnetic, up-conversion and down-conversion materials for multimodal imaging. in Scientific Reports. 2019;9(1):1-15.
doi:10.1038/s41598-019-52885-0
https://hdl.handle.net/21.15107/rcub_dais_6950 .

Ignjatović, Nenad, Mančić, Lidija, Vuković, Marina, Stojanović, Zoran S., Nikolić, Marko G., Škapin, Srečo Davor, Jovanović, Sonja, Veselinović, Ljiljana, Uskoković, Vuk, Lazić, Snežana, Marković, Smilja, Lazarević, Miloš M., Uskoković, Dragan, "Rare-earth (Gd 3+ ,Yb 3+ /Tm 3+ , Eu 3+ ) co-doped hydroxyapatite as magnetic, up-conversion and down-conversion materials for multimodal imaging" in Scientific Reports, 9, no. 1 (2019):1-15,
https://doi.org/10.1038/s41598-019-52885-0 .,
https://hdl.handle.net/21.15107/rcub_dais_6950 .