Biocompatible Germanium-Doped Hydroxyapatite Nanoparticles for Promoting Osteogenic Differentiation and Antimicrobial Activity
2024
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Аутори
Lazarević, Miloš M.Ignjatović, Nenad
Mahlet, Qene
Bumah, Violet V.
Radunović, Milena
Milašin, Jelena
Uskoković, Dragan
Uskoković, Vuk
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
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, whe...n 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.
Кључне речи:
antibacterial effect / antifungal effect / calcium phosphate / doping / flow cytometry / nanomedicine / tissue engineeringИзвор:
ACS Applied Nano Materials, 2024Издавач:
- American Chemical Society (ACS)
Финансирање / пројекти:
- ORCA-PCR - Oral cancer: New approaches in prevention, control and post-operative regeneration: An in vitro study (RS-ScienceFundRS-Ideje-7750038)
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200129 (Универзитет у Београду, Стоматолошки факултет) (RS-MESTD-inst-2020-200129)
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200175 (Институт техничких наука САНУ, Београд) (RS-MESTD-inst-2020-200175)
DOI: 10.1021/acsanm.3c05974
ISSN: 2574-0970; 2574-0970
Scopus: 2-s2.0-85189991215
Институција/група
Институт техничких наука САНУ / Institute of Technical Sciences of SASATY - 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 .