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  - JOUR
AU  - Lazarević, Miloš
AU  - Petrović, Sanja
AU  - Pierfelice, Tania Vanessa
AU  - Ignjatović, Nenad
AU  - Piattelli, Adriano
AU  - Vlajić Tovilović, Tamara
AU  - Radunović, Milena
PY  - 2023
UR  - https://dais.sanu.ac.rs/123456789/14287
AB  - Collagen membranes are routinely used in oral surgery for bone regeneration. Despite their numerous advantages, such as stimulating bone growth, bacterial contamination still remains one of the disadvantages of membrane use. Thus, we assessed the biocompatibility and osteogenic and antibacterial properties of a collagen membrane (OsteoBiol) modified with chitosan (CHI) and hydroxyapatite nanoparticles (HApNPs). Attenuated total reflectance-Fourier transform infrared spectroscopy (ATR FT-IR), X-ray powder diffraction (XRD), and field emission scanning electron microscopy (FE-SEM) were performed for membrane characterization. Biocompatibility was assessed on dental pulp stem cells (DPSCs) by an MTT assay, while the osteogenic effect was assessed by an ALP activity assay and qPCR analysis of osteogenic markers (BMP4, ALP, RUNX2, and OCN). Antimicrobial properties were investigated by counting colony-forming units (CFUs) of Streptococcus mitis, Porphyromonas gingivalis, and Fusobaterium nucleatum on membranes and in the surrounding medium. Membranes showed no cytotoxicity. ALP activity was higher and ALP, BMP4, and OCN genes were up-regulated in DPSCs on modified membranes compared to unmodified membranes. The CFUs were reduced on modified membranes and in the medium. Modified membranes showed great biocompatibility and a high osteoinductive effect. Additionally, they showed antimicrobial and antibiofilm effects against periopathogens. It can be concluded that the incorporation of CHI and hydroxyapatite nanoparticles in collagen membranes may be advantageous to promote osteogenesis and reduce bacterial adhesion.
PB  - Basel : MDPI AG
T2  - Biomolecules
T1  - Antimicrobial and Osteogenic Effects of Collagen Membrane Decorated with Chitosan–Nano-Hydroxyapatite
SP  - 579
VL  - 13
IS  - 4
DO  - 10.3390/biom13040579
UR  - https://hdl.handle.net/21.15107/rcub_dais_14287
ER  - 

@article{
author = "Lazarević, Miloš and Petrović, Sanja and Pierfelice, Tania Vanessa and Ignjatović, Nenad and Piattelli, Adriano and Vlajić Tovilović, Tamara and Radunović, Milena",
year = "2023",
abstract = "Collagen membranes are routinely used in oral surgery for bone regeneration. Despite their numerous advantages, such as stimulating bone growth, bacterial contamination still remains one of the disadvantages of membrane use. Thus, we assessed the biocompatibility and osteogenic and antibacterial properties of a collagen membrane (OsteoBiol) modified with chitosan (CHI) and hydroxyapatite nanoparticles (HApNPs). Attenuated total reflectance-Fourier transform infrared spectroscopy (ATR FT-IR), X-ray powder diffraction (XRD), and field emission scanning electron microscopy (FE-SEM) were performed for membrane characterization. Biocompatibility was assessed on dental pulp stem cells (DPSCs) by an MTT assay, while the osteogenic effect was assessed by an ALP activity assay and qPCR analysis of osteogenic markers (BMP4, ALP, RUNX2, and OCN). Antimicrobial properties were investigated by counting colony-forming units (CFUs) of Streptococcus mitis, Porphyromonas gingivalis, and Fusobaterium nucleatum on membranes and in the surrounding medium. Membranes showed no cytotoxicity. ALP activity was higher and ALP, BMP4, and OCN genes were up-regulated in DPSCs on modified membranes compared to unmodified membranes. The CFUs were reduced on modified membranes and in the medium. Modified membranes showed great biocompatibility and a high osteoinductive effect. Additionally, they showed antimicrobial and antibiofilm effects against periopathogens. It can be concluded that the incorporation of CHI and hydroxyapatite nanoparticles in collagen membranes may be advantageous to promote osteogenesis and reduce bacterial adhesion.",
publisher = "Basel : MDPI AG",
journal = "Biomolecules",
title = "Antimicrobial and Osteogenic Effects of Collagen Membrane Decorated with Chitosan–Nano-Hydroxyapatite",
pages = "579",
volume = "13",
number = "4",
doi = "10.3390/biom13040579",
url = "https://hdl.handle.net/21.15107/rcub_dais_14287"
}

Lazarević, M., Petrović, S., Pierfelice, T. V., Ignjatović, N., Piattelli, A., Vlajić Tovilović, T.,& Radunović, M.. (2023). Antimicrobial and Osteogenic Effects of Collagen Membrane Decorated with Chitosan–Nano-Hydroxyapatite. in Biomolecules
Basel : MDPI AG., 13(4), 579.
https://doi.org/10.3390/biom13040579
https://hdl.handle.net/21.15107/rcub_dais_14287

Lazarević M, Petrović S, Pierfelice TV, Ignjatović N, Piattelli A, Vlajić Tovilović T, Radunović M. Antimicrobial and Osteogenic Effects of Collagen Membrane Decorated with Chitosan–Nano-Hydroxyapatite. in Biomolecules. 2023;13(4):579.
doi:10.3390/biom13040579
https://hdl.handle.net/21.15107/rcub_dais_14287 .

Lazarević, Miloš, Petrović, Sanja, Pierfelice, Tania Vanessa, Ignjatović, Nenad, Piattelli, Adriano, Vlajić Tovilović, Tamara, Radunović, Milena, "Antimicrobial and Osteogenic Effects of Collagen Membrane Decorated with Chitosan–Nano-Hydroxyapatite" in Biomolecules, 13, no. 4 (2023):579,
https://doi.org/10.3390/biom13040579 .,
https://hdl.handle.net/21.15107/rcub_dais_14287 .