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  - Uskoković, Vuk
AU  - Ignjatović, Nenad
AU  - Škapin, Srečo
AU  - Uskoković, Dragan
PY  - 2022
UR  - https://dais.sanu.ac.rs/123456789/13563
AB  - Hydroxyapatite (HAp) is the major component of all boney tissues in mammals. Because of this omnipresence in the living world, HAp possesses an exceptional biocompatibility. The downside of this omnipresence, however, comes in the form of its mild to moderate biological activities. One means of augmenting these activities involves the doping of HAp with foreign ions. Here, the first synthesis and characterization of HAp doped with germanium ions is being reported. Germanium was deliberately integrated into the crystal lattice of HAp in the form of germanate anions. Approximately two thirds of the germanate ions introduced into the hydrothermal solution got incorporated into the HAp lattice, yielding the approximate stoichiometry of Ca10-x(PO4)5.62+y(GeO3)0.38(OH)2-z. Germanates replaced the phosphates of stoichiometric HAp and induced the expansion of the HAp lattice both along the screw axis of the calcium ion hexagons and in the direction parallel to the basal plane. Simultaneously, the larger size and the triple valency of the germanate ion as compared to the smaller and trivalent phosphates prompted the bond distortion and charge compensation through defect formation, which reduced the crystallinity and increased the microstrain of the HAp lattice. Vibrational spectroscopic analyses corroborated these crystallographic effects by demonstrating the enhanced heterogeneity of the environments surrounding the active modes after germanate ions were incorporated into HAp. Conforming to La Châtelier's principle, this reduction of the crystallographic order increased the capacity of the material for integration of adventitious carbonates. However, the inclusion of germanate ions induced a partial shift of these carbonates to the hydroxyl channel sites, thus decreasing the ratio of the B-type carbonation to the A-type carbonation. Introduced into HAp, germanium acted as a superb regulator of the particle size and morphology, enhancing their fineness and uniformity. Inclusion of germanate ions also increased the electrophoretic mobility and hydrodynamic surface charge density of the particles by reducing their size and by inducing a more stochastic distribution of terminal ionic groups due to the bending of the crystal facets. Overall, the doping of HAp with germanate ions facilitated the production of narrowly dispersed nanorods with a moderately enhanced structural disorder and with a pronounced potential for the biomedical niche. © 2022 The Author(s)
T2  - Ceramics International
T1  - Germanium-doped hydroxyapatite: Synthesis and characterization of a new substituted apatite
SP  - 27693
EP  - 27702
VL  - 48
IS  - 19
DO  - 10.1016/j.ceramint.2022.06.068
UR  - https://hdl.handle.net/21.15107/rcub_dais_13563
ER  - 

@article{
author = "Uskoković, Vuk and Ignjatović, Nenad and Škapin, Srečo and Uskoković, Dragan",
year = "2022",
abstract = "Hydroxyapatite (HAp) is the major component of all boney tissues in mammals. Because of this omnipresence in the living world, HAp possesses an exceptional biocompatibility. The downside of this omnipresence, however, comes in the form of its mild to moderate biological activities. One means of augmenting these activities involves the doping of HAp with foreign ions. Here, the first synthesis and characterization of HAp doped with germanium ions is being reported. Germanium was deliberately integrated into the crystal lattice of HAp in the form of germanate anions. Approximately two thirds of the germanate ions introduced into the hydrothermal solution got incorporated into the HAp lattice, yielding the approximate stoichiometry of Ca10-x(PO4)5.62+y(GeO3)0.38(OH)2-z. Germanates replaced the phosphates of stoichiometric HAp and induced the expansion of the HAp lattice both along the screw axis of the calcium ion hexagons and in the direction parallel to the basal plane. Simultaneously, the larger size and the triple valency of the germanate ion as compared to the smaller and trivalent phosphates prompted the bond distortion and charge compensation through defect formation, which reduced the crystallinity and increased the microstrain of the HAp lattice. Vibrational spectroscopic analyses corroborated these crystallographic effects by demonstrating the enhanced heterogeneity of the environments surrounding the active modes after germanate ions were incorporated into HAp. Conforming to La Châtelier's principle, this reduction of the crystallographic order increased the capacity of the material for integration of adventitious carbonates. However, the inclusion of germanate ions induced a partial shift of these carbonates to the hydroxyl channel sites, thus decreasing the ratio of the B-type carbonation to the A-type carbonation. Introduced into HAp, germanium acted as a superb regulator of the particle size and morphology, enhancing their fineness and uniformity. Inclusion of germanate ions also increased the electrophoretic mobility and hydrodynamic surface charge density of the particles by reducing their size and by inducing a more stochastic distribution of terminal ionic groups due to the bending of the crystal facets. Overall, the doping of HAp with germanate ions facilitated the production of narrowly dispersed nanorods with a moderately enhanced structural disorder and with a pronounced potential for the biomedical niche. © 2022 The Author(s)",
journal = "Ceramics International",
title = "Germanium-doped hydroxyapatite: Synthesis and characterization of a new substituted apatite",
pages = "27693-27702",
volume = "48",
number = "19",
doi = "10.1016/j.ceramint.2022.06.068",
url = "https://hdl.handle.net/21.15107/rcub_dais_13563"
}

Uskoković, V., Ignjatović, N., Škapin, S.,& Uskoković, D.. (2022). Germanium-doped hydroxyapatite: Synthesis and characterization of a new substituted apatite. in Ceramics International, 48(19), 27693-27702.
https://doi.org/10.1016/j.ceramint.2022.06.068
https://hdl.handle.net/21.15107/rcub_dais_13563

Uskoković V, Ignjatović N, Škapin S, Uskoković D. Germanium-doped hydroxyapatite: Synthesis and characterization of a new substituted apatite. in Ceramics International. 2022;48(19):27693-27702.
doi:10.1016/j.ceramint.2022.06.068
https://hdl.handle.net/21.15107/rcub_dais_13563 .

Uskoković, Vuk, Ignjatović, Nenad, Škapin, Srečo, Uskoković, Dragan, "Germanium-doped hydroxyapatite: Synthesis and characterization of a new substituted apatite" in Ceramics International, 48, no. 19 (2022):27693-27702,
https://doi.org/10.1016/j.ceramint.2022.06.068 .,
https://hdl.handle.net/21.15107/rcub_dais_13563 .

TY  - JOUR
AU  - Degli Esposti, Lorenzo
AU  - Marković, Smilja
AU  - Ignjatović, Nenad
AU  - Panseri, Silvia
AU  - Montesi, Monica
AU  - Adamiano, Alessio
AU  - Fosca, Marco
AU  - Rau, Julietta V.
AU  - Uskoković, Vuk
AU  - Iafisco, Michele
PY  - 2021
UR  - https://dais.sanu.ac.rs/123456789/11639
AB  - Amorphous calcium phosphate (ACP) is a material of high interest for dentistry, orthopedics, and other biomedical sectors. Being intrinsically metastable, the process of transformation of ACP into a crystalline phase upon heating is of high relevance for the development of innovative bioceramics. Here we have first studied the thermal behavior of a citrate-stabilized ACP (Cit-ACP) also doped with fluoride ions (Cit-FACP) prepared at three different nominal Cit/Ca ratios (i.e. 4, 2, 1) by differential thermal analysis. Next, the physico-chemical features of the crystalline products as well as the in vitro cell response to the materials were investigated. A citrate and fluoride free ACP sample was also tested as the blank. We have found that the activation energy of crystallization of Cit-(F)ACP samples is lower in comparison to the blank ACP and this is influenced by the nominal Cit/Ca molar ratio. Interestingly, we have discovered that the thermal treatment of Cit-(F)ACP at 800 °C yields hydroxyapatite (HA) or fluorapatite (FHA) as the main products differently from blank ACP that, like most of the ACPs reported in the literature, yields β-tricalcium phosphate. This was attributed to the Ca/P ratio of Cit-(F)ACP, which is similar to HA. A study of the crystalline products has revealed that all the (F)HA samples were non-cytotoxic, and retained carbonate ions in the crystal structure despite the heat treatment that should have induced decarbonation. The morphology of the products is influenced by the nominal Cit/Ca ratio and the presence of fluoride, ranging from spherical nanoparticles to micrometric hexagonal rods. Overall, our results prove that the thermal crystallization of Cit-(F)ACP is markedly different from classic ACP based materials and the thermal treatment of Cit-(F)ACP represents an attractive route for producing pure bioactive HA ceramics.
PB  - Royal Society of Chemistry
T2  - Journal of Materials Chemistry B
T1  - Thermal crystallization of amorphous calcium phosphate combined with citrate and fluoride doping: a novel route to produce hydroxyapatite bioceramics
SP  - 4832
EP  - 4845
VL  - 9
IS  - 24
DO  - 10.1039/D1TB00601K
UR  - https://hdl.handle.net/21.15107/rcub_dais_11639
ER  - 

@article{
author = "Degli Esposti, Lorenzo and Marković, Smilja and Ignjatović, Nenad and Panseri, Silvia and Montesi, Monica and Adamiano, Alessio and Fosca, Marco and Rau, Julietta V. and Uskoković, Vuk and Iafisco, Michele",
year = "2021",
abstract = "Amorphous calcium phosphate (ACP) is a material of high interest for dentistry, orthopedics, and other biomedical sectors. Being intrinsically metastable, the process of transformation of ACP into a crystalline phase upon heating is of high relevance for the development of innovative bioceramics. Here we have first studied the thermal behavior of a citrate-stabilized ACP (Cit-ACP) also doped with fluoride ions (Cit-FACP) prepared at three different nominal Cit/Ca ratios (i.e. 4, 2, 1) by differential thermal analysis. Next, the physico-chemical features of the crystalline products as well as the in vitro cell response to the materials were investigated. A citrate and fluoride free ACP sample was also tested as the blank. We have found that the activation energy of crystallization of Cit-(F)ACP samples is lower in comparison to the blank ACP and this is influenced by the nominal Cit/Ca molar ratio. Interestingly, we have discovered that the thermal treatment of Cit-(F)ACP at 800 °C yields hydroxyapatite (HA) or fluorapatite (FHA) as the main products differently from blank ACP that, like most of the ACPs reported in the literature, yields β-tricalcium phosphate. This was attributed to the Ca/P ratio of Cit-(F)ACP, which is similar to HA. A study of the crystalline products has revealed that all the (F)HA samples were non-cytotoxic, and retained carbonate ions in the crystal structure despite the heat treatment that should have induced decarbonation. The morphology of the products is influenced by the nominal Cit/Ca ratio and the presence of fluoride, ranging from spherical nanoparticles to micrometric hexagonal rods. Overall, our results prove that the thermal crystallization of Cit-(F)ACP is markedly different from classic ACP based materials and the thermal treatment of Cit-(F)ACP represents an attractive route for producing pure bioactive HA ceramics.",
publisher = "Royal Society of Chemistry",
journal = "Journal of Materials Chemistry B",
title = "Thermal crystallization of amorphous calcium phosphate combined with citrate and fluoride doping: a novel route to produce hydroxyapatite bioceramics",
pages = "4832-4845",
volume = "9",
number = "24",
doi = "10.1039/D1TB00601K",
url = "https://hdl.handle.net/21.15107/rcub_dais_11639"
}

Degli Esposti, L., Marković, S., Ignjatović, N., Panseri, S., Montesi, M., Adamiano, A., Fosca, M., Rau, J. V., Uskoković, V.,& Iafisco, M.. (2021). Thermal crystallization of amorphous calcium phosphate combined with citrate and fluoride doping: a novel route to produce hydroxyapatite bioceramics. in Journal of Materials Chemistry B
Royal Society of Chemistry., 9(24), 4832-4845.
https://doi.org/10.1039/D1TB00601K
https://hdl.handle.net/21.15107/rcub_dais_11639

Degli Esposti L, Marković S, Ignjatović N, Panseri S, Montesi M, Adamiano A, Fosca M, Rau JV, Uskoković V, Iafisco M. Thermal crystallization of amorphous calcium phosphate combined with citrate and fluoride doping: a novel route to produce hydroxyapatite bioceramics. in Journal of Materials Chemistry B. 2021;9(24):4832-4845.
doi:10.1039/D1TB00601K
https://hdl.handle.net/21.15107/rcub_dais_11639 .

Degli Esposti, Lorenzo, Marković, Smilja, Ignjatović, Nenad, Panseri, Silvia, Montesi, Monica, Adamiano, Alessio, Fosca, Marco, Rau, Julietta V., Uskoković, Vuk, Iafisco, Michele, "Thermal crystallization of amorphous calcium phosphate combined with citrate and fluoride doping: a novel route to produce hydroxyapatite bioceramics" in Journal of Materials Chemistry B, 9, no. 24 (2021):4832-4845,
https://doi.org/10.1039/D1TB00601K .,
https://hdl.handle.net/21.15107/rcub_dais_11639 .

TY  - JOUR
AU  - Degli Esposti, Lorenzo
AU  - Marković, Smilja
AU  - Ignjatović, Nenad
AU  - Panseri, Silvia
AU  - Montesi, Monica
AU  - Adamiano, Alessio
AU  - Fosca, Marco
AU  - Rau, Julietta V.
AU  - Uskoković, Vuk
AU  - Iafisco, Michele
PY  - 2021
UR  - https://dais.sanu.ac.rs/123456789/11640
AB  - Amorphous calcium phosphate (ACP) is a material of high interest for dentistry, orthopedics, and other biomedical sectors. Being intrinsically metastable, the process of transformation of ACP into a crystalline phase upon heating is of high relevance for the development of innovative bioceramics. Here we have first studied the thermal behavior of a citrate-stabilized ACP (Cit-ACP) also doped with fluoride ions (Cit-FACP) prepared at three different nominal Cit/Ca ratios (i.e. 4, 2, 1) by differential thermal analysis. Next, the physico-chemical features of the crystalline products as well as the in vitro cell response to the materials were investigated. A citrate and fluoride free ACP sample was also tested as the blank. We have found that the activation energy of crystallization of Cit-(F)ACP samples is lower in comparison to the blank ACP and this is influenced by the nominal Cit/Ca molar ratio. Interestingly, we have discovered that the thermal treatment of Cit-(F)ACP at 800 °C yields hydroxyapatite (HA) or fluorapatite (FHA) as the main products differently from blank ACP that, like most of the ACPs reported in the literature, yields β-tricalcium phosphate. This was attributed to the Ca/P ratio of Cit-(F)ACP, which is similar to HA. A study of the crystalline products has revealed that all the (F)HA samples were non-cytotoxic, and retained carbonate ions in the crystal structure despite the heat treatment that should have induced decarbonation. The morphology of the products is influenced by the nominal Cit/Ca ratio and the presence of fluoride, ranging from spherical nanoparticles to micrometric hexagonal rods. Overall, our results prove that the thermal crystallization of Cit-(F)ACP is markedly different from classic ACP based materials and the thermal treatment of Cit-(F)ACP represents an attractive route for producing pure bioactive HA ceramics.
PB  - Royal Society of Chemistry
T2  - Journal of Materials Chemistry B
T1  - Thermal crystallization of amorphous calcium phosphate combined with citrate and fluoride doping: a novel route to produce hydroxyapatite bioceramics
SP  - 4832
EP  - 4845
VL  - 9
IS  - 24
DO  - 10.1039/D1TB00601K
UR  - https://hdl.handle.net/21.15107/rcub_dais_11640
ER  - 

@article{
author = "Degli Esposti, Lorenzo and Marković, Smilja and Ignjatović, Nenad and Panseri, Silvia and Montesi, Monica and Adamiano, Alessio and Fosca, Marco and Rau, Julietta V. and Uskoković, Vuk and Iafisco, Michele",
year = "2021",
abstract = "Amorphous calcium phosphate (ACP) is a material of high interest for dentistry, orthopedics, and other biomedical sectors. Being intrinsically metastable, the process of transformation of ACP into a crystalline phase upon heating is of high relevance for the development of innovative bioceramics. Here we have first studied the thermal behavior of a citrate-stabilized ACP (Cit-ACP) also doped with fluoride ions (Cit-FACP) prepared at three different nominal Cit/Ca ratios (i.e. 4, 2, 1) by differential thermal analysis. Next, the physico-chemical features of the crystalline products as well as the in vitro cell response to the materials were investigated. A citrate and fluoride free ACP sample was also tested as the blank. We have found that the activation energy of crystallization of Cit-(F)ACP samples is lower in comparison to the blank ACP and this is influenced by the nominal Cit/Ca molar ratio. Interestingly, we have discovered that the thermal treatment of Cit-(F)ACP at 800 °C yields hydroxyapatite (HA) or fluorapatite (FHA) as the main products differently from blank ACP that, like most of the ACPs reported in the literature, yields β-tricalcium phosphate. This was attributed to the Ca/P ratio of Cit-(F)ACP, which is similar to HA. A study of the crystalline products has revealed that all the (F)HA samples were non-cytotoxic, and retained carbonate ions in the crystal structure despite the heat treatment that should have induced decarbonation. The morphology of the products is influenced by the nominal Cit/Ca ratio and the presence of fluoride, ranging from spherical nanoparticles to micrometric hexagonal rods. Overall, our results prove that the thermal crystallization of Cit-(F)ACP is markedly different from classic ACP based materials and the thermal treatment of Cit-(F)ACP represents an attractive route for producing pure bioactive HA ceramics.",
publisher = "Royal Society of Chemistry",
journal = "Journal of Materials Chemistry B",
title = "Thermal crystallization of amorphous calcium phosphate combined with citrate and fluoride doping: a novel route to produce hydroxyapatite bioceramics",
pages = "4832-4845",
volume = "9",
number = "24",
doi = "10.1039/D1TB00601K",
url = "https://hdl.handle.net/21.15107/rcub_dais_11640"
}

Degli Esposti, L., Marković, S., Ignjatović, N., Panseri, S., Montesi, M., Adamiano, A., Fosca, M., Rau, J. V., Uskoković, V.,& Iafisco, M.. (2021). Thermal crystallization of amorphous calcium phosphate combined with citrate and fluoride doping: a novel route to produce hydroxyapatite bioceramics. in Journal of Materials Chemistry B
Royal Society of Chemistry., 9(24), 4832-4845.
https://doi.org/10.1039/D1TB00601K
https://hdl.handle.net/21.15107/rcub_dais_11640

Degli Esposti L, Marković S, Ignjatović N, Panseri S, Montesi M, Adamiano A, Fosca M, Rau JV, Uskoković V, Iafisco M. Thermal crystallization of amorphous calcium phosphate combined with citrate and fluoride doping: a novel route to produce hydroxyapatite bioceramics. in Journal of Materials Chemistry B. 2021;9(24):4832-4845.
doi:10.1039/D1TB00601K
https://hdl.handle.net/21.15107/rcub_dais_11640 .

Degli Esposti, Lorenzo, Marković, Smilja, Ignjatović, Nenad, Panseri, Silvia, Montesi, Monica, Adamiano, Alessio, Fosca, Marco, Rau, Julietta V., Uskoković, Vuk, Iafisco, Michele, "Thermal crystallization of amorphous calcium phosphate combined with citrate and fluoride doping: a novel route to produce hydroxyapatite bioceramics" in Journal of Materials Chemistry B, 9, no. 24 (2021):4832-4845,
https://doi.org/10.1039/D1TB00601K .,
https://hdl.handle.net/21.15107/rcub_dais_11640 .

TY  - DATA
AU  - Degli Esposti, Lorenzo
AU  - Marković, Smilja
AU  - Ignjatović, Nenad
AU  - Panseri, Silvia
AU  - Montesi, Monica
AU  - Adamiano, Alessio
AU  - Fosca, Marco
AU  - Rau, Julietta V.
AU  - Uskoković, Vuk
AU  - Iafisco, Michele
PY  - 2021
UR  - https://dais.sanu.ac.rs/123456789/11642
AB  - Figure S1. The shift in the crystallization peak for (A) Cit-ACP-1 and (B) Cit-FACP-1 to higher temperatures in direct proportion with the heating rate; Figure S2. TGA curves of calcined Cit-ACP-4, Cit-ACP-2, and Cit-ACP-1; Figure S3. Pictures of calcined (A) Cit-ACP-4 and (B) Cit-ACP-1
PB  - Royal Society of Chemistry
T2  - Journal of Materials Chemistry B
T1  - Electronic Supplementary Information associated with the article: Degli Esposti Lorenzo, Marković Smilja, Ignjatović Nenad, Panseri Silvia, Montesi Monica, Adamiano Alessio, Fosca Marco, Rau Julietta V., Uskoković Vuk, Iafisco Michele, "Thermal crystallization of amorphous calcium phosphate combined with citrate and fluoride doping: a novel route to produce hydroxyapatite bioceramics." Journal of Materials Chemistry B, 9, no. 24 (2021):4832-4845, https://doi.org/10.1039/D1TB00601K
VL  - 9
IS  - 24
UR  - https://hdl.handle.net/21.15107/rcub_dais_11642
ER  - 

@misc{
author = "Degli Esposti, Lorenzo and Marković, Smilja and Ignjatović, Nenad and Panseri, Silvia and Montesi, Monica and Adamiano, Alessio and Fosca, Marco and Rau, Julietta V. and Uskoković, Vuk and Iafisco, Michele",
year = "2021",
abstract = "Figure S1. The shift in the crystallization peak for (A) Cit-ACP-1 and (B) Cit-FACP-1 to higher temperatures in direct proportion with the heating rate; Figure S2. TGA curves of calcined Cit-ACP-4, Cit-ACP-2, and Cit-ACP-1; Figure S3. Pictures of calcined (A) Cit-ACP-4 and (B) Cit-ACP-1",
publisher = "Royal Society of Chemistry",
journal = "Journal of Materials Chemistry B",
title = "Electronic Supplementary Information associated with the article: Degli Esposti Lorenzo, Marković Smilja, Ignjatović Nenad, Panseri Silvia, Montesi Monica, Adamiano Alessio, Fosca Marco, Rau Julietta V., Uskoković Vuk, Iafisco Michele, "Thermal crystallization of amorphous calcium phosphate combined with citrate and fluoride doping: a novel route to produce hydroxyapatite bioceramics." Journal of Materials Chemistry B, 9, no. 24 (2021):4832-4845, https://doi.org/10.1039/D1TB00601K",
volume = "9",
number = "24",
url = "https://hdl.handle.net/21.15107/rcub_dais_11642"
}

Degli Esposti, L., Marković, S., Ignjatović, N., Panseri, S., Montesi, M., Adamiano, A., Fosca, M., Rau, J. V., Uskoković, V.,& Iafisco, M.. (2021). Electronic Supplementary Information associated with the article: Degli Esposti Lorenzo, Marković Smilja, Ignjatović Nenad, Panseri Silvia, Montesi Monica, Adamiano Alessio, Fosca Marco, Rau Julietta V., Uskoković Vuk, Iafisco Michele, "Thermal crystallization of amorphous calcium phosphate combined with citrate and fluoride doping: a novel route to produce hydroxyapatite bioceramics." Journal of Materials Chemistry B, 9, no. 24 (2021):4832-4845, https://doi.org/10.1039/D1TB00601K. in Journal of Materials Chemistry B
Royal Society of Chemistry., 9(24).
https://hdl.handle.net/21.15107/rcub_dais_11642

Degli Esposti L, Marković S, Ignjatović N, Panseri S, Montesi M, Adamiano A, Fosca M, Rau JV, Uskoković V, Iafisco M. Electronic Supplementary Information associated with the article: Degli Esposti Lorenzo, Marković Smilja, Ignjatović Nenad, Panseri Silvia, Montesi Monica, Adamiano Alessio, Fosca Marco, Rau Julietta V., Uskoković Vuk, Iafisco Michele, "Thermal crystallization of amorphous calcium phosphate combined with citrate and fluoride doping: a novel route to produce hydroxyapatite bioceramics." Journal of Materials Chemistry B, 9, no. 24 (2021):4832-4845, https://doi.org/10.1039/D1TB00601K. in Journal of Materials Chemistry B. 2021;9(24).
https://hdl.handle.net/21.15107/rcub_dais_11642 .

Degli Esposti, Lorenzo, Marković, Smilja, Ignjatović, Nenad, Panseri, Silvia, Montesi, Monica, Adamiano, Alessio, Fosca, Marco, Rau, Julietta V., Uskoković, Vuk, Iafisco, Michele, "Electronic Supplementary Information associated with the article: Degli Esposti Lorenzo, Marković Smilja, Ignjatović Nenad, Panseri Silvia, Montesi Monica, Adamiano Alessio, Fosca Marco, Rau Julietta V., Uskoković Vuk, Iafisco Michele, "Thermal crystallization of amorphous calcium phosphate combined with citrate and fluoride doping: a novel route to produce hydroxyapatite bioceramics." Journal of Materials Chemistry B, 9, no. 24 (2021):4832-4845, https://doi.org/10.1039/D1TB00601K" in Journal of Materials Chemistry B, 9, no. 24 (2021),
https://hdl.handle.net/21.15107/rcub_dais_11642 .

TY  - JOUR
AU  - Ignjatović, Nenad
AU  - Marković, Smilja
AU  - Jugović, Dragana
AU  - Uskoković, Vuk
AU  - Uskoković, Dragan
PY  - 2020
UR  - https://dais.sanu.ac.rs/123456789/10037
AB  - Functional nanomaterials have held a steady position at the frontier of materials science and engineering in the 21st century. “Molecular Designing of Nanoparticles with Controlled Morphological and Physicochemical Characteristics and Functional Materials Based on Them” was the title of the research project funded by the Ministry of Education, Science and Technological Development of the Republic of Serbia and performed between 2011 and 2019 in the interdisciplinary area of nanoscience and nanotechnologies. Research activities within this program were divided into five interrelated topics: 1) from molecules to nanoparticles; 2) advanced ceramics with improved functional properties; 3) electrode materials for lithium–ion batteries; 4) nano-calcium phosphate in preventive and regenerative medicine; 5) biodegradable microand nano-particles for the controlled delivery of medicaments. This report gives an insight into this bibliographically most impactful Serbian national project on nanotechnologies executed within the aforementioned nine-year cycle, 2011–2019, focusing here only on the results achieved in the past three years. The project provided an outstanding and internationally recognized contribution to synthesis, characterization and functional design of a number of materials systems, including pure and lanthanide–doped hydroxyapatite, zinc oxides, sodium cobaltates, lithium iron pyrophosphates, lithium iron silicates and a number of polymeric systems.
PB  - Belgrade : Serbian Chemical Society
T2  - Journal of the Serbian Chemical Society
T1  - From molecules to nanoparticles to functional materials
SP  - 1383
EP  - 1403
VL  - 85
IS  - 11
DO  - 10.2298/JSC200426035I
UR  - https://hdl.handle.net/21.15107/rcub_dais_10037
ER  - 

@article{
author = "Ignjatović, Nenad and Marković, Smilja and Jugović, Dragana and Uskoković, Vuk and Uskoković, Dragan",
year = "2020",
abstract = "Functional nanomaterials have held a steady position at the frontier of materials science and engineering in the 21st century. “Molecular Designing of Nanoparticles with Controlled Morphological and Physicochemical Characteristics and Functional Materials Based on Them” was the title of the research project funded by the Ministry of Education, Science and Technological Development of the Republic of Serbia and performed between 2011 and 2019 in the interdisciplinary area of nanoscience and nanotechnologies. Research activities within this program were divided into five interrelated topics: 1) from molecules to nanoparticles; 2) advanced ceramics with improved functional properties; 3) electrode materials for lithium–ion batteries; 4) nano-calcium phosphate in preventive and regenerative medicine; 5) biodegradable microand nano-particles for the controlled delivery of medicaments. This report gives an insight into this bibliographically most impactful Serbian national project on nanotechnologies executed within the aforementioned nine-year cycle, 2011–2019, focusing here only on the results achieved in the past three years. The project provided an outstanding and internationally recognized contribution to synthesis, characterization and functional design of a number of materials systems, including pure and lanthanide–doped hydroxyapatite, zinc oxides, sodium cobaltates, lithium iron pyrophosphates, lithium iron silicates and a number of polymeric systems.",
publisher = "Belgrade : Serbian Chemical Society",
journal = "Journal of the Serbian Chemical Society",
title = "From molecules to nanoparticles to functional materials",
pages = "1383-1403",
volume = "85",
number = "11",
doi = "10.2298/JSC200426035I",
url = "https://hdl.handle.net/21.15107/rcub_dais_10037"
}

Ignjatović, N., Marković, S., Jugović, D., Uskoković, V.,& Uskoković, D.. (2020). From molecules to nanoparticles to functional materials. in Journal of the Serbian Chemical Society
Belgrade : Serbian Chemical Society., 85(11), 1383-1403.
https://doi.org/10.2298/JSC200426035I
https://hdl.handle.net/21.15107/rcub_dais_10037

Ignjatović N, Marković S, Jugović D, Uskoković V, Uskoković D. From molecules to nanoparticles to functional materials. in Journal of the Serbian Chemical Society. 2020;85(11):1383-1403.
doi:10.2298/JSC200426035I
https://hdl.handle.net/21.15107/rcub_dais_10037 .

Ignjatović, Nenad, Marković, Smilja, Jugović, Dragana, Uskoković, Vuk, Uskoković, Dragan, "From molecules to nanoparticles to functional materials" in Journal of the Serbian Chemical Society, 85, no. 11 (2020):1383-1403,
https://doi.org/10.2298/JSC200426035I .,
https://hdl.handle.net/21.15107/rcub_dais_10037 .

TY  - JOUR
AU  - Uskoković, Vuk
AU  - Tang, Sean
AU  - Nikolić, Marko G.
AU  - Marković, Smilja
AU  - Wu, Victoria M.
PY  - 2019
UR  - https://avs.scitation.org/doi/abs/10.1116/1.5090396
UR  - https://dais.sanu.ac.rs/123456789/6468
AB  - One of the main goals of materials science in the 21st century is the development of materials with rationally designed properties as substitutes for traditional pharmacotherapies. At the same time, there is a lack of understanding of the exact material properties that induce therapeutic effects in biological systems, which limits their rational optimization for the related medical applications. This study sets the foundation for a general approach for elucidating nanoparticle properties as determinants of antibacterial activity, with a particular focus on calcium phosphate nanoparticles. To that end, nine physicochemical effects were studied and a number of them were refuted, thus putting an end to frequently erred hypotheses in the literature. Rather than having one key particle property responsible for eliciting the antibacterial effect, a complex synergy of factors is shown to be at work, including (a) nanoscopic size; (b) elevated intracellular free calcium levels due to nanoparticle solubility; (c) diffusivity and favorable electrostatic properties of the nanoparticle surface, primarily low net charge and high charge density; and (d) the dynamics of perpetual exchange of ultrafine clusters across the particle/solution interface. On the positive side, this multifaceted mechanism is less prone to induce bacterial resistance to the therapy and can be a gateway to the sphere of personalized medicine. On a more problematic side, it implies a less intense effect compared to single-target molecular therapies and a difficulty of elucidating the exact mechanisms of action, while also making the rational design of theirs for this type of medical application a challenge.
PB  - AIP Publishing LLC
T2  - Biointerphases
T1  - Calcium phosphate nanoparticles as intrinsic inorganic antimicrobials: In search of the key particle property
SP  - 031001
VL  - 14
IS  - 3
DO  - 10.1116/1.5090396
UR  - https://hdl.handle.net/21.15107/rcub_dais_6468
ER  - 

@article{
author = "Uskoković, Vuk and Tang, Sean and Nikolić, Marko G. and Marković, Smilja and Wu, Victoria M.",
year = "2019",
abstract = "One of the main goals of materials science in the 21st century is the development of materials with rationally designed properties as substitutes for traditional pharmacotherapies. At the same time, there is a lack of understanding of the exact material properties that induce therapeutic effects in biological systems, which limits their rational optimization for the related medical applications. This study sets the foundation for a general approach for elucidating nanoparticle properties as determinants of antibacterial activity, with a particular focus on calcium phosphate nanoparticles. To that end, nine physicochemical effects were studied and a number of them were refuted, thus putting an end to frequently erred hypotheses in the literature. Rather than having one key particle property responsible for eliciting the antibacterial effect, a complex synergy of factors is shown to be at work, including (a) nanoscopic size; (b) elevated intracellular free calcium levels due to nanoparticle solubility; (c) diffusivity and favorable electrostatic properties of the nanoparticle surface, primarily low net charge and high charge density; and (d) the dynamics of perpetual exchange of ultrafine clusters across the particle/solution interface. On the positive side, this multifaceted mechanism is less prone to induce bacterial resistance to the therapy and can be a gateway to the sphere of personalized medicine. On a more problematic side, it implies a less intense effect compared to single-target molecular therapies and a difficulty of elucidating the exact mechanisms of action, while also making the rational design of theirs for this type of medical application a challenge.",
publisher = "AIP Publishing LLC",
journal = "Biointerphases",
title = "Calcium phosphate nanoparticles as intrinsic inorganic antimicrobials: In search of the key particle property",
pages = "031001",
volume = "14",
number = "3",
doi = "10.1116/1.5090396",
url = "https://hdl.handle.net/21.15107/rcub_dais_6468"
}

Uskoković, V., Tang, S., Nikolić, M. G., Marković, S.,& Wu, V. M.. (2019). Calcium phosphate nanoparticles as intrinsic inorganic antimicrobials: In search of the key particle property. in Biointerphases
AIP Publishing LLC., 14(3), 031001.
https://doi.org/10.1116/1.5090396
https://hdl.handle.net/21.15107/rcub_dais_6468

Uskoković V, Tang S, Nikolić MG, Marković S, Wu VM. Calcium phosphate nanoparticles as intrinsic inorganic antimicrobials: In search of the key particle property. in Biointerphases. 2019;14(3):031001.
doi:10.1116/1.5090396
https://hdl.handle.net/21.15107/rcub_dais_6468 .

Uskoković, Vuk, Tang, Sean, Nikolić, Marko G., Marković, Smilja, Wu, Victoria M., "Calcium phosphate nanoparticles as intrinsic inorganic antimicrobials: In search of the key particle property" in Biointerphases, 14, no. 3 (2019):031001,
https://doi.org/10.1116/1.5090396 .,
https://hdl.handle.net/21.15107/rcub_dais_6468 .

TY  - JOUR
AU  - Uskoković, Vuk
AU  - Tang, Sean
AU  - Nikolić, Marko G.
AU  - Marković, Smilja
AU  - Wu, Victoria M.
PY  - 2019
UR  - https://avs.scitation.org/doi/abs/10.1116/1.5090396
UR  - https://dais.sanu.ac.rs/123456789/6469
AB  - One of the main goals of materials science in the 21st century is the development of materials with rationally designed properties as substitutes for traditional pharmacotherapies. At the same time, there is a lack of understanding of the exact material properties that induce therapeutic effects in biological systems, which limits their rational optimization for the related medical applications. This study sets the foundation for a general approach for elucidating nanoparticle properties as determinants of antibacterial activity, with a particular focus on calcium phosphate nanoparticles. To that end, nine physicochemical effects were studied and a number of them were refuted, thus putting an end to frequently erred hypotheses in the literature. Rather than having one key particle property responsible for eliciting the antibacterial effect, a complex synergy of factors is shown to be at work, including (a) nanoscopic size; (b) elevated intracellular free calcium levels due to nanoparticle solubility; (c) diffusivity and favorable electrostatic properties of the nanoparticle surface, primarily low net charge and high charge density; and (d) the dynamics of perpetual exchange of ultrafine clusters across the particle/solution interface. On the positive side, this multifaceted mechanism is less prone to induce bacterial resistance to the therapy and can be a gateway to the sphere of personalized medicine. On a more problematic side, it implies a less intense effect compared to single-target molecular therapies and a difficulty of elucidating the exact mechanisms of action, while also making the rational design of theirs for this type of medical application a challenge.
PB  - AIP Publishing LLC
T2  - Biointerphases
T1  - Calcium phosphate nanoparticles as intrinsic inorganic antimicrobials: In search of the key particle property
SP  - 031001
VL  - 14
IS  - 3
DO  - 10.1116/1.5090396
UR  - https://hdl.handle.net/21.15107/rcub_dais_6469
ER  - 

@article{
author = "Uskoković, Vuk and Tang, Sean and Nikolić, Marko G. and Marković, Smilja and Wu, Victoria M.",
year = "2019",
abstract = "One of the main goals of materials science in the 21st century is the development of materials with rationally designed properties as substitutes for traditional pharmacotherapies. At the same time, there is a lack of understanding of the exact material properties that induce therapeutic effects in biological systems, which limits their rational optimization for the related medical applications. This study sets the foundation for a general approach for elucidating nanoparticle properties as determinants of antibacterial activity, with a particular focus on calcium phosphate nanoparticles. To that end, nine physicochemical effects were studied and a number of them were refuted, thus putting an end to frequently erred hypotheses in the literature. Rather than having one key particle property responsible for eliciting the antibacterial effect, a complex synergy of factors is shown to be at work, including (a) nanoscopic size; (b) elevated intracellular free calcium levels due to nanoparticle solubility; (c) diffusivity and favorable electrostatic properties of the nanoparticle surface, primarily low net charge and high charge density; and (d) the dynamics of perpetual exchange of ultrafine clusters across the particle/solution interface. On the positive side, this multifaceted mechanism is less prone to induce bacterial resistance to the therapy and can be a gateway to the sphere of personalized medicine. On a more problematic side, it implies a less intense effect compared to single-target molecular therapies and a difficulty of elucidating the exact mechanisms of action, while also making the rational design of theirs for this type of medical application a challenge.",
publisher = "AIP Publishing LLC",
journal = "Biointerphases",
title = "Calcium phosphate nanoparticles as intrinsic inorganic antimicrobials: In search of the key particle property",
pages = "031001",
volume = "14",
number = "3",
doi = "10.1116/1.5090396",
url = "https://hdl.handle.net/21.15107/rcub_dais_6469"
}

Uskoković, V., Tang, S., Nikolić, M. G., Marković, S.,& Wu, V. M.. (2019). Calcium phosphate nanoparticles as intrinsic inorganic antimicrobials: In search of the key particle property. in Biointerphases
AIP Publishing LLC., 14(3), 031001.
https://doi.org/10.1116/1.5090396
https://hdl.handle.net/21.15107/rcub_dais_6469

Uskoković V, Tang S, Nikolić MG, Marković S, Wu VM. Calcium phosphate nanoparticles as intrinsic inorganic antimicrobials: In search of the key particle property. in Biointerphases. 2019;14(3):031001.
doi:10.1116/1.5090396
https://hdl.handle.net/21.15107/rcub_dais_6469 .

Uskoković, Vuk, Tang, Sean, Nikolić, Marko G., Marković, Smilja, Wu, Victoria M., "Calcium phosphate nanoparticles as intrinsic inorganic antimicrobials: In search of the key particle property" in Biointerphases, 14, no. 3 (2019):031001,
https://doi.org/10.1116/1.5090396 .,
https://hdl.handle.net/21.15107/rcub_dais_6469 .

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 .

TY  - JOUR
AU  - Ignjatović, Nenad
AU  - Janković, Radmila
AU  - Uskoković, Vuk
AU  - Uskoković, Dragan
PY  - 2019
UR  - https://pubs.rsc.org/en/content/articlelanding/2019/tx/c9tx00007k
UR  - https://dais.sanu.ac.rs/123456789/4961
AB  - Reconstruction of bone defects with the use of biomaterials based on hydroxyapatite (HAp) has been a popular approach in medicine and dentistry. Most often the process of new bone formation is analyzed with the focus only on the region of the reconstructed defect. The effects of the therapy on distant organs have been rarely reported in literature, especially not in synergy with the exposure to other bioactive chemicals. In this study, reconstruction of the mandibular bone in vivo using poly-lactide-co-glycolide-coated HAp (HAp/PLGA) nanoparticles was monitored with a simultaneous histopathological analysis of distant organs, specifically kidney and liver parenchyma. Heavy metals are among the most prominent environmental pollutants and have a high affinity for the crystal lattice of HAp, where they get incorporated by replacing calcium ions. Lead (Pb) and cadmium (Cd) are two such metals that can be found in food, water and air, but are most commonly present in cigarette smoke, the frequent contaminant of hospital settings in the developing world. A study performed on 24 female Wistar rats demonstrated that the reconstruction of mandibular bone defects using HAp/PLGA particles induced an increase in the content of Ca in the newly created bone without causing any pathological changes to the liver and the kidneys. The presence of Pb and Cd in the defects reconstructed with HAp/PLGA nanoparticles impeded the regenerative process and led to a severe and irreversible damage to the liver and kidney parenchyma.
T2  - Toxicology Research
T1  - Effects of Hydroxyapatite@Poly-Lactide-Co-Glycolide Nanoparticles Combined with Pb and Cd on Liver and Kidney Parenchyma after the Reconstruction of Mandibular Bone Defects
SP  - 287
EP  - 296
VL  - 8
DO  - 10.1039/C9TX00007K
UR  - https://hdl.handle.net/21.15107/rcub_dais_4961
ER  - 

@article{
author = "Ignjatović, Nenad and Janković, Radmila and Uskoković, Vuk and Uskoković, Dragan",
year = "2019",
abstract = "Reconstruction of bone defects with the use of biomaterials based on hydroxyapatite (HAp) has been a popular approach in medicine and dentistry. Most often the process of new bone formation is analyzed with the focus only on the region of the reconstructed defect. The effects of the therapy on distant organs have been rarely reported in literature, especially not in synergy with the exposure to other bioactive chemicals. In this study, reconstruction of the mandibular bone in vivo using poly-lactide-co-glycolide-coated HAp (HAp/PLGA) nanoparticles was monitored with a simultaneous histopathological analysis of distant organs, specifically kidney and liver parenchyma. Heavy metals are among the most prominent environmental pollutants and have a high affinity for the crystal lattice of HAp, where they get incorporated by replacing calcium ions. Lead (Pb) and cadmium (Cd) are two such metals that can be found in food, water and air, but are most commonly present in cigarette smoke, the frequent contaminant of hospital settings in the developing world. A study performed on 24 female Wistar rats demonstrated that the reconstruction of mandibular bone defects using HAp/PLGA particles induced an increase in the content of Ca in the newly created bone without causing any pathological changes to the liver and the kidneys. The presence of Pb and Cd in the defects reconstructed with HAp/PLGA nanoparticles impeded the regenerative process and led to a severe and irreversible damage to the liver and kidney parenchyma.",
journal = "Toxicology Research",
title = "Effects of Hydroxyapatite@Poly-Lactide-Co-Glycolide Nanoparticles Combined with Pb and Cd on Liver and Kidney Parenchyma after the Reconstruction of Mandibular Bone Defects",
pages = "287-296",
volume = "8",
doi = "10.1039/C9TX00007K",
url = "https://hdl.handle.net/21.15107/rcub_dais_4961"
}

Ignjatović, N., Janković, R., Uskoković, V.,& Uskoković, D.. (2019). Effects of Hydroxyapatite@Poly-Lactide-Co-Glycolide Nanoparticles Combined with Pb and Cd on Liver and Kidney Parenchyma after the Reconstruction of Mandibular Bone Defects. in Toxicology Research, 8, 287-296.
https://doi.org/10.1039/C9TX00007K
https://hdl.handle.net/21.15107/rcub_dais_4961

Ignjatović N, Janković R, Uskoković V, Uskoković D. Effects of Hydroxyapatite@Poly-Lactide-Co-Glycolide Nanoparticles Combined with Pb and Cd on Liver and Kidney Parenchyma after the Reconstruction of Mandibular Bone Defects. in Toxicology Research. 2019;8:287-296.
doi:10.1039/C9TX00007K
https://hdl.handle.net/21.15107/rcub_dais_4961 .

Ignjatović, Nenad, Janković, Radmila, Uskoković, Vuk, Uskoković, Dragan, "Effects of Hydroxyapatite@Poly-Lactide-Co-Glycolide Nanoparticles Combined with Pb and Cd on Liver and Kidney Parenchyma after the Reconstruction of Mandibular Bone Defects" in Toxicology Research, 8 (2019):287-296,
https://doi.org/10.1039/C9TX00007K .,
https://hdl.handle.net/21.15107/rcub_dais_4961 .

TY  - JOUR
AU  - Ignjatović, Nenad
AU  - Janković, Radmila
AU  - Uskoković, Vuk
AU  - Uskoković, Dragan
PY  - 2019
UR  - https://pubs.rsc.org/en/content/articlelanding/2019/tx/c9tx00007k
UR  - https://dais.sanu.ac.rs/123456789/4847
AB  - Reconstruction of bone defects with the use of biomaterials based on hydroxyapatite (HAp) has been a popular approach in medicine and dentistry. Most often the process of new bone formation is analyzed with the focus only on the region of the reconstructed defect. The effects of the therapy on distant organs have been rarely reported in literature, especially not in synergy with the exposure to other bioactive chemicals. In this study, reconstruction of the mandibular bone in vivo using poly-lactide-co-glycolide-coated HAp (HAp/PLGA) nanoparticles was monitored with a simultaneous histopathological analysis of distant organs, specifically kidney and liver parenchyma. Heavy metals are among the most prominent environmental pollutants and have a high affinity for the crystal lattice of HAp, where they get incorporated by replacing calcium ions. Lead (Pb) and cadmium (Cd) are two such metals that can be found in food, water and air, but are most commonly present in cigarette smoke, the frequent contaminant of hospital settings in the developing world. A study performed on 24 female Wistar rats demonstrated that the reconstruction of mandibular bone defects using HAp/PLGA particles induced an increase in the content of Ca in the newly created bone without causing any pathological changes to the liver and the kidneys. The presence of Pb and Cd in the defects reconstructed with HAp/PLGA nanoparticles impeded the regenerative process and led to a severe and irreversible damage to the liver and kidney parenchyma.
T2  - Toxicology Research
T1  - Effects of Hydroxyapatite@Poly-Lactide-Co-Glycolide Nanoparticles Combined with Pb and Cd on Liver and Kidney Parenchyma after the Reconstruction of Mandibular Bone Defects
SP  - 287
EP  - 296
VL  - 8
DO  - 10.1039/C9TX00007K
UR  - https://hdl.handle.net/21.15107/rcub_dais_4847
ER  - 

@article{
author = "Ignjatović, Nenad and Janković, Radmila and Uskoković, Vuk and Uskoković, Dragan",
year = "2019",
abstract = "Reconstruction of bone defects with the use of biomaterials based on hydroxyapatite (HAp) has been a popular approach in medicine and dentistry. Most often the process of new bone formation is analyzed with the focus only on the region of the reconstructed defect. The effects of the therapy on distant organs have been rarely reported in literature, especially not in synergy with the exposure to other bioactive chemicals. In this study, reconstruction of the mandibular bone in vivo using poly-lactide-co-glycolide-coated HAp (HAp/PLGA) nanoparticles was monitored with a simultaneous histopathological analysis of distant organs, specifically kidney and liver parenchyma. Heavy metals are among the most prominent environmental pollutants and have a high affinity for the crystal lattice of HAp, where they get incorporated by replacing calcium ions. Lead (Pb) and cadmium (Cd) are two such metals that can be found in food, water and air, but are most commonly present in cigarette smoke, the frequent contaminant of hospital settings in the developing world. A study performed on 24 female Wistar rats demonstrated that the reconstruction of mandibular bone defects using HAp/PLGA particles induced an increase in the content of Ca in the newly created bone without causing any pathological changes to the liver and the kidneys. The presence of Pb and Cd in the defects reconstructed with HAp/PLGA nanoparticles impeded the regenerative process and led to a severe and irreversible damage to the liver and kidney parenchyma.",
journal = "Toxicology Research",
title = "Effects of Hydroxyapatite@Poly-Lactide-Co-Glycolide Nanoparticles Combined with Pb and Cd on Liver and Kidney Parenchyma after the Reconstruction of Mandibular Bone Defects",
pages = "287-296",
volume = "8",
doi = "10.1039/C9TX00007K",
url = "https://hdl.handle.net/21.15107/rcub_dais_4847"
}

Ignjatović, N., Janković, R., Uskoković, V.,& Uskoković, D.. (2019). Effects of Hydroxyapatite@Poly-Lactide-Co-Glycolide Nanoparticles Combined with Pb and Cd on Liver and Kidney Parenchyma after the Reconstruction of Mandibular Bone Defects. in Toxicology Research, 8, 287-296.
https://doi.org/10.1039/C9TX00007K
https://hdl.handle.net/21.15107/rcub_dais_4847

Ignjatović N, Janković R, Uskoković V, Uskoković D. Effects of Hydroxyapatite@Poly-Lactide-Co-Glycolide Nanoparticles Combined with Pb and Cd on Liver and Kidney Parenchyma after the Reconstruction of Mandibular Bone Defects. in Toxicology Research. 2019;8:287-296.
doi:10.1039/C9TX00007K
https://hdl.handle.net/21.15107/rcub_dais_4847 .

Ignjatović, Nenad, Janković, Radmila, Uskoković, Vuk, Uskoković, Dragan, "Effects of Hydroxyapatite@Poly-Lactide-Co-Glycolide Nanoparticles Combined with Pb and Cd on Liver and Kidney Parenchyma after the Reconstruction of Mandibular Bone Defects" in Toxicology Research, 8 (2019):287-296,
https://doi.org/10.1039/C9TX00007K .,
https://hdl.handle.net/21.15107/rcub_dais_4847 .

TY  - JOUR
AU  - Ignjatović, Nenad
AU  - Sakač, Marija
AU  - Kuzminac, Ivana
AU  - Kojić, Vesna
AU  - Marković, Smilja
AU  - Vasiljević Radović, Dana
AU  - Wu, Victoria M.
AU  - Uskoković, Vuk
AU  - Uskoković, Dragan
PY  - 2018
UR  - https://pubs.rsc.org/en/content/articlelanding/2018/tb/c8tb01995a
UR  - https://dais.sanu.ac.rs/123456789/4509
AB  - Low targeting efficiency and fast metabolism of antineoplastic drugs are hindrances to effective chemotherapies and there is an ongoing search for better drugs, but also better carriers. Steroid derivatives, 3β-hydroxy-16-hydroxymino-androst-5-en-17-one (A) and 3β,17β-dihydroxy-16-hydroxymino-androst-5-ene (B) as cancer growth inhibitors were chemically synthesized and captured in a carrier composed of hydroxyapatite (HAp) nanoparticles coated with chitosan oligosaccharide lactate (ChOLS). The only difference between the two derivatives is that A has a carbonyl group at the C17 position of the five-membered ring and B has a hydroxyl. This small difference in the structure resulted not only in different physicochemical properties of the A- and B-loaded HAp/ChOSL, but also in different biological activities. The morphology of drug-loaded HAp/ChOSL particles was spherical, but the size depended on the drug identity: d50 = 138 nm for A-loaded HAp/ChOSL and d50 = 223 nm for B-loaded HAp/ChOSL. Cell-selective toxicity was tested against human breast carcinoma (MCF7 and MDA-MB-231), human lung carcinoma (A549) and human lung fibroblasts (MRC-5). The small selectivity of pure derivatives A and B toward breast cancer cells became drastically increased when they were delivered using HAp/ChOSL particles. Whereas the ratio of the cytotoxicity imposed onto breast cancer cells and the cytotoxicity imposed onto healthy MRC-5 fibroblasts ranged from 1.5 to 1.7 for pure A and from 1.5 to 2.3 for pure derivative B depending on the concentration, it increased to 5.4 for A-loaded HAp/ChOSL and 5.1 for B-loaded HAp/ChOSL. FACS analysis demonstrated poor uptake of HAp/ChOSL particles by MCF7 cells, suggesting that the drug release occurs extracellularly. The augmented activity of the drugs was most likely due to sustained release, although the favorable positive charge of the carrier, allowing it to adhere to the negatively charged plasma membrane and release the drugs steadily and directly to the hydrophobic cell membrane milieu, was delineated as a possible complementary mechanism.
PB  - Royal Society of Chemistry
T2  - Journal of Materials Chemistry B
T1  - Chitosan oligosaccharide lactate coated hydroxyapatite nanoparticles as a vehicle for the delivery of steroid drugs and the targeting of breast cancer cells
SP  - 6957
EP  - 696
VL  - 6
DO  - 10.1039/C8TB01995A
UR  - https://hdl.handle.net/21.15107/rcub_dais_4509
ER  - 

@article{
author = "Ignjatović, Nenad and Sakač, Marija and Kuzminac, Ivana and Kojić, Vesna and Marković, Smilja and Vasiljević Radović, Dana and Wu, Victoria M. and Uskoković, Vuk and Uskoković, Dragan",
year = "2018",
abstract = "Low targeting efficiency and fast metabolism of antineoplastic drugs are hindrances to effective chemotherapies and there is an ongoing search for better drugs, but also better carriers. Steroid derivatives, 3β-hydroxy-16-hydroxymino-androst-5-en-17-one (A) and 3β,17β-dihydroxy-16-hydroxymino-androst-5-ene (B) as cancer growth inhibitors were chemically synthesized and captured in a carrier composed of hydroxyapatite (HAp) nanoparticles coated with chitosan oligosaccharide lactate (ChOLS). The only difference between the two derivatives is that A has a carbonyl group at the C17 position of the five-membered ring and B has a hydroxyl. This small difference in the structure resulted not only in different physicochemical properties of the A- and B-loaded HAp/ChOSL, but also in different biological activities. The morphology of drug-loaded HAp/ChOSL particles was spherical, but the size depended on the drug identity: d50 = 138 nm for A-loaded HAp/ChOSL and d50 = 223 nm for B-loaded HAp/ChOSL. Cell-selective toxicity was tested against human breast carcinoma (MCF7 and MDA-MB-231), human lung carcinoma (A549) and human lung fibroblasts (MRC-5). The small selectivity of pure derivatives A and B toward breast cancer cells became drastically increased when they were delivered using HAp/ChOSL particles. Whereas the ratio of the cytotoxicity imposed onto breast cancer cells and the cytotoxicity imposed onto healthy MRC-5 fibroblasts ranged from 1.5 to 1.7 for pure A and from 1.5 to 2.3 for pure derivative B depending on the concentration, it increased to 5.4 for A-loaded HAp/ChOSL and 5.1 for B-loaded HAp/ChOSL. FACS analysis demonstrated poor uptake of HAp/ChOSL particles by MCF7 cells, suggesting that the drug release occurs extracellularly. The augmented activity of the drugs was most likely due to sustained release, although the favorable positive charge of the carrier, allowing it to adhere to the negatively charged plasma membrane and release the drugs steadily and directly to the hydrophobic cell membrane milieu, was delineated as a possible complementary mechanism.",
publisher = "Royal Society of Chemistry",
journal = "Journal of Materials Chemistry B",
title = "Chitosan oligosaccharide lactate coated hydroxyapatite nanoparticles as a vehicle for the delivery of steroid drugs and the targeting of breast cancer cells",
pages = "6957-696",
volume = "6",
doi = "10.1039/C8TB01995A",
url = "https://hdl.handle.net/21.15107/rcub_dais_4509"
}

Ignjatović, N., Sakač, M., Kuzminac, I., Kojić, V., Marković, S., Vasiljević Radović, D., Wu, V. M., Uskoković, V.,& Uskoković, D.. (2018). Chitosan oligosaccharide lactate coated hydroxyapatite nanoparticles as a vehicle for the delivery of steroid drugs and the targeting of breast cancer cells. in Journal of Materials Chemistry B
Royal Society of Chemistry., 6, 6957-696.
https://doi.org/10.1039/C8TB01995A
https://hdl.handle.net/21.15107/rcub_dais_4509

Ignjatović N, Sakač M, Kuzminac I, Kojić V, Marković S, Vasiljević Radović D, Wu VM, Uskoković V, Uskoković D. Chitosan oligosaccharide lactate coated hydroxyapatite nanoparticles as a vehicle for the delivery of steroid drugs and the targeting of breast cancer cells. in Journal of Materials Chemistry B. 2018;6:6957-696.
doi:10.1039/C8TB01995A
https://hdl.handle.net/21.15107/rcub_dais_4509 .

Ignjatović, Nenad, Sakač, Marija, Kuzminac, Ivana, Kojić, Vesna, Marković, Smilja, Vasiljević Radović, Dana, Wu, Victoria M., Uskoković, Vuk, Uskoković, Dragan, "Chitosan oligosaccharide lactate coated hydroxyapatite nanoparticles as a vehicle for the delivery of steroid drugs and the targeting of breast cancer cells" in Journal of Materials Chemistry B, 6 (2018):6957-696,
https://doi.org/10.1039/C8TB01995A .,
https://hdl.handle.net/21.15107/rcub_dais_4509 .

TY  - JOUR
AU  - Ignjatović, Nenad
AU  - Sakač, Marija
AU  - Kuzminac, Ivana
AU  - Kojić, Vesna
AU  - Marković, Smilja
AU  - Vasiljević Radović, Dana
AU  - Wu, Victoria
AU  - Uskoković, Vuk
AU  - Uskoković, Dragan
PY  - 2018
UR  - https://dais.sanu.ac.rs/123456789/4066
AB  - Low targeting efficiency and fast metabolism of antineoplastic drugs are hindrances to effective chemotherapies and there is an ongoing search for better drugs, but also better carriers. Steroid derivatives, 3β-hydroxy-16-hydroxymino-androst-5-en-17-one (A) and 3β,17β-dihydroxy-16-hydroxymino-androst-5-ene (B) as cancer growth inhibitors were chemically synthesized and captured in a carrier composed of hydroxyapatite (HAp) nanoparticles coated with chitosan oligosaccharide lactate (ChOLS). The only difference between the two derivatives is that A has a carbonyl group at the C17 position of the five-membered ring and B has a hydroxyl. This small difference in the structure resulted not only in different physicochemical properties of the A- and B-loaded HAp/ChOSL, but also in different biological activities. The morphology of drug-loaded HAp/ChOSL particles was spherical, but the size depended on the drug identity: d50 = 138 nm for A-loaded HAp/ChOSL and d50 = 223 nm for B-loaded HAp/ChOSL. Cell-selective toxicity was tested against human breast carcinoma (MCF7 and MDA-MB-231), human lung carcinoma (A549) and human lung fibroblasts (MRC-5). The small selectivity of pure derivatives A and B toward breast cancer cells became drastically increased when they were delivered using HAp/ChOSL particles. Whereas the ratio of the cytotoxicity imposed onto breast cancer cells and the cytotoxicity imposed onto healthy MRC-5 fibroblasts ranged from 1.5 to 1.7 for pure A and from 1.5 to 2.3 for pure derivative B depending on the concentration, it increased to 5.4 for A-loaded HAp/ChOSL and 5.1 for B-loaded HAp/ChOSL. FACS analysis demonstrated poor uptake of HAp/ChOSL particles by MCF7 cells, suggesting that the drug release occurs extracellularly. The augmented activity of the drugs was most likely due to sustained release, although the favorable positive charge of the carrier, allowing it to adhere to the negatively charged plasma membrane and release the drugs steadily and directly to the hydrophobic cell membrane milieu, was delineated as a possible complementary mechanism.
PB  - Royal Society of Chemistry
T2  - Journal of Materials Chemistry B
T1  - Chitosan oligosaccharide lactate coated hydroxyapatite nanoparticles as a vehicle for the delivery of steroid drugs and the targeting of breast cancer cells
SP  - 6957
EP  - 6968
VL  - 6
DO  - 10.1039/C8TB01995A
UR  - https://hdl.handle.net/21.15107/rcub_dais_4066
ER  - 

@article{
author = "Ignjatović, Nenad and Sakač, Marija and Kuzminac, Ivana and Kojić, Vesna and Marković, Smilja and Vasiljević Radović, Dana and Wu, Victoria and Uskoković, Vuk and Uskoković, Dragan",
year = "2018",
abstract = "Low targeting efficiency and fast metabolism of antineoplastic drugs are hindrances to effective chemotherapies and there is an ongoing search for better drugs, but also better carriers. Steroid derivatives, 3β-hydroxy-16-hydroxymino-androst-5-en-17-one (A) and 3β,17β-dihydroxy-16-hydroxymino-androst-5-ene (B) as cancer growth inhibitors were chemically synthesized and captured in a carrier composed of hydroxyapatite (HAp) nanoparticles coated with chitosan oligosaccharide lactate (ChOLS). The only difference between the two derivatives is that A has a carbonyl group at the C17 position of the five-membered ring and B has a hydroxyl. This small difference in the structure resulted not only in different physicochemical properties of the A- and B-loaded HAp/ChOSL, but also in different biological activities. The morphology of drug-loaded HAp/ChOSL particles was spherical, but the size depended on the drug identity: d50 = 138 nm for A-loaded HAp/ChOSL and d50 = 223 nm for B-loaded HAp/ChOSL. Cell-selective toxicity was tested against human breast carcinoma (MCF7 and MDA-MB-231), human lung carcinoma (A549) and human lung fibroblasts (MRC-5). The small selectivity of pure derivatives A and B toward breast cancer cells became drastically increased when they were delivered using HAp/ChOSL particles. Whereas the ratio of the cytotoxicity imposed onto breast cancer cells and the cytotoxicity imposed onto healthy MRC-5 fibroblasts ranged from 1.5 to 1.7 for pure A and from 1.5 to 2.3 for pure derivative B depending on the concentration, it increased to 5.4 for A-loaded HAp/ChOSL and 5.1 for B-loaded HAp/ChOSL. FACS analysis demonstrated poor uptake of HAp/ChOSL particles by MCF7 cells, suggesting that the drug release occurs extracellularly. The augmented activity of the drugs was most likely due to sustained release, although the favorable positive charge of the carrier, allowing it to adhere to the negatively charged plasma membrane and release the drugs steadily and directly to the hydrophobic cell membrane milieu, was delineated as a possible complementary mechanism.",
publisher = "Royal Society of Chemistry",
journal = "Journal of Materials Chemistry B",
title = "Chitosan oligosaccharide lactate coated hydroxyapatite nanoparticles as a vehicle for the delivery of steroid drugs and the targeting of breast cancer cells",
pages = "6957-6968",
volume = "6",
doi = "10.1039/C8TB01995A",
url = "https://hdl.handle.net/21.15107/rcub_dais_4066"
}

Ignjatović, N., Sakač, M., Kuzminac, I., Kojić, V., Marković, S., Vasiljević Radović, D., Wu, V., Uskoković, V.,& Uskoković, D.. (2018). Chitosan oligosaccharide lactate coated hydroxyapatite nanoparticles as a vehicle for the delivery of steroid drugs and the targeting of breast cancer cells. in Journal of Materials Chemistry B
Royal Society of Chemistry., 6, 6957-6968.
https://doi.org/10.1039/C8TB01995A
https://hdl.handle.net/21.15107/rcub_dais_4066

Ignjatović N, Sakač M, Kuzminac I, Kojić V, Marković S, Vasiljević Radović D, Wu V, Uskoković V, Uskoković D. Chitosan oligosaccharide lactate coated hydroxyapatite nanoparticles as a vehicle for the delivery of steroid drugs and the targeting of breast cancer cells. in Journal of Materials Chemistry B. 2018;6:6957-6968.
doi:10.1039/C8TB01995A
https://hdl.handle.net/21.15107/rcub_dais_4066 .

Ignjatović, Nenad, Sakač, Marija, Kuzminac, Ivana, Kojić, Vesna, Marković, Smilja, Vasiljević Radović, Dana, Wu, Victoria, Uskoković, Vuk, Uskoković, Dragan, "Chitosan oligosaccharide lactate coated hydroxyapatite nanoparticles as a vehicle for the delivery of steroid drugs and the targeting of breast cancer cells" in Journal of Materials Chemistry B, 6 (2018):6957-6968,
https://doi.org/10.1039/C8TB01995A .,
https://hdl.handle.net/21.15107/rcub_dais_4066 .

TY  - CONF
AU  - Ignjatović, Nenad
AU  - Sakač, Marija
AU  - Kuzminac, Ivana
AU  - Kojić, Vesna V.
AU  - Marković, Smilja
AU  - Wu, Victoria
AU  - Uskoković, Vuk
AU  - Uskoković, Dragan
PY  - 2018
UR  - https://dais.sanu.ac.rs/123456789/3662
AB  - The applicative potential of synthetic calcium phosphates, especially hydroxyapatite (HAp), has become intensely broadened in the past 10 years, from bone tissue engineering to multiple other fields of biomedicine. Hybrid systems based on nano hydroxyapatites (HAp) are the subject of numerous studies in preventive and regenerative medicine. HAp nanoparticles coated with bioresorbable polymers have been successfully used as fillers, carriers of antibiotics, vitamins and stem cells in bone tissue engineering, etc. In this study we utilize an emulsification process and freeze drying to load the hybrid system made of nano HAp particles coated with chitosan oligosaccharide lactate (ChOSL) with two different but similar steroid derivatives: 3β-hydroxy- 16-hydroxymino-androst-5-ene-17-one (A), C19H27NO3 and 3β, 17β-dihydroxy-16-hydroxyminoandrost- 5-ene (B), C19H29NO3. The cell-selective toxicity of HAp particles coated with of A- or B-loaded ChOSL was examined simultaneously on the following cell lines: human breast carcinoma (MCF-7, MDA-MB-231), human lung carcinoma (A549) and human lung fibroblasts (MRC-5), using dye exclusion (DET) and MTT assays. 1H NMR, 13C NMR and high-resolution time-of-flight mass spectrometry (MS) techniques confirmed the intact structure of the derivatives A or B. FT-IR, XRD, DTA, TGA and DSC techniques confirmed the drug loading process of steroide (A or B) in core–shell particles based on nano hydroxyapatite. Atomic force microscopy and particle size analyses were used to confirm that the particles were spherical with sizes between 80 and 240 nm. The measured values of electrokinetic parameters (zeta potential, electrophoretic mobility and conductivity) were significantly different for the steroid free carrier (HAp/ChOLS) and A- or B-loaded ChOSL. The value of the topological molecular polar surface area (TPSA, the sum of the surfaces of polar atoms and groups in the molecule), were also different for drug free carrier and A- or BHAp/ ChOLS. Highly selective anticancer activity was noted towards breast cancer cells (MDAMB- 231) by B-loaded HAp/ChOLS. DET testing after 48 hours (after incubation and recovery) of the treatment with A-HAp/ChOSL and B-HAp/ChOSL particles showed a high viability of healthy cells (over 80%). The lowest viability was found in MDA-MB-231 cancer cells treated with B-HAp/ChOSL (28%). The obtained results of the DET and MTT tests showed that the particles of A-HAp/ChOLS exhibited nearly four-fold greater cytotoxicity towards breast cancer cells (MDA-MB-231) than towards healthy cells (MRC-5). B-HAp/ChOSL particles exhibited nearly six times greater cytotoxicity to all breast cancer cells than to healthy ones.
PB  - Belgrade : Materials Research Society of Serbia
C3  - Programme and The Book of Abstracts / Twentieth Annual Conference YUCOMAT 2018, Herceg Novi, September 3-7, 2018
T1  - Cell-selective toxicity of hydroxyapatite-chitosan oligosaccharide lactate particles loaded with a steroid cancer inhibitor
SP  - 74
EP  - 75
UR  - https://hdl.handle.net/21.15107/rcub_dais_3662
ER  - 

@conference{
author = "Ignjatović, Nenad and Sakač, Marija and Kuzminac, Ivana and Kojić, Vesna V. and Marković, Smilja and Wu, Victoria and Uskoković, Vuk and Uskoković, Dragan",
year = "2018",
abstract = "The applicative potential of synthetic calcium phosphates, especially hydroxyapatite (HAp), has become intensely broadened in the past 10 years, from bone tissue engineering to multiple other fields of biomedicine. Hybrid systems based on nano hydroxyapatites (HAp) are the subject of numerous studies in preventive and regenerative medicine. HAp nanoparticles coated with bioresorbable polymers have been successfully used as fillers, carriers of antibiotics, vitamins and stem cells in bone tissue engineering, etc. In this study we utilize an emulsification process and freeze drying to load the hybrid system made of nano HAp particles coated with chitosan oligosaccharide lactate (ChOSL) with two different but similar steroid derivatives: 3β-hydroxy- 16-hydroxymino-androst-5-ene-17-one (A), C19H27NO3 and 3β, 17β-dihydroxy-16-hydroxyminoandrost- 5-ene (B), C19H29NO3. The cell-selective toxicity of HAp particles coated with of A- or B-loaded ChOSL was examined simultaneously on the following cell lines: human breast carcinoma (MCF-7, MDA-MB-231), human lung carcinoma (A549) and human lung fibroblasts (MRC-5), using dye exclusion (DET) and MTT assays. 1H NMR, 13C NMR and high-resolution time-of-flight mass spectrometry (MS) techniques confirmed the intact structure of the derivatives A or B. FT-IR, XRD, DTA, TGA and DSC techniques confirmed the drug loading process of steroide (A or B) in core–shell particles based on nano hydroxyapatite. Atomic force microscopy and particle size analyses were used to confirm that the particles were spherical with sizes between 80 and 240 nm. The measured values of electrokinetic parameters (zeta potential, electrophoretic mobility and conductivity) were significantly different for the steroid free carrier (HAp/ChOLS) and A- or B-loaded ChOSL. The value of the topological molecular polar surface area (TPSA, the sum of the surfaces of polar atoms and groups in the molecule), were also different for drug free carrier and A- or BHAp/ ChOLS. Highly selective anticancer activity was noted towards breast cancer cells (MDAMB- 231) by B-loaded HAp/ChOLS. DET testing after 48 hours (after incubation and recovery) of the treatment with A-HAp/ChOSL and B-HAp/ChOSL particles showed a high viability of healthy cells (over 80%). The lowest viability was found in MDA-MB-231 cancer cells treated with B-HAp/ChOSL (28%). The obtained results of the DET and MTT tests showed that the particles of A-HAp/ChOLS exhibited nearly four-fold greater cytotoxicity towards breast cancer cells (MDA-MB-231) than towards healthy cells (MRC-5). B-HAp/ChOSL particles exhibited nearly six times greater cytotoxicity to all breast cancer cells than to healthy ones.",
publisher = "Belgrade : Materials Research Society of Serbia",
journal = "Programme and The Book of Abstracts / Twentieth Annual Conference YUCOMAT 2018, Herceg Novi, September 3-7, 2018",
title = "Cell-selective toxicity of hydroxyapatite-chitosan oligosaccharide lactate particles loaded with a steroid cancer inhibitor",
pages = "74-75",
url = "https://hdl.handle.net/21.15107/rcub_dais_3662"
}

Ignjatović, N., Sakač, M., Kuzminac, I., Kojić, V. V., Marković, S., Wu, V., Uskoković, V.,& Uskoković, D.. (2018). Cell-selective toxicity of hydroxyapatite-chitosan oligosaccharide lactate particles loaded with a steroid cancer inhibitor. in Programme and The Book of Abstracts / Twentieth Annual Conference YUCOMAT 2018, Herceg Novi, September 3-7, 2018
Belgrade : Materials Research Society of Serbia., 74-75.
https://hdl.handle.net/21.15107/rcub_dais_3662

Ignjatović N, Sakač M, Kuzminac I, Kojić VV, Marković S, Wu V, Uskoković V, Uskoković D. Cell-selective toxicity of hydroxyapatite-chitosan oligosaccharide lactate particles loaded with a steroid cancer inhibitor. in Programme and The Book of Abstracts / Twentieth Annual Conference YUCOMAT 2018, Herceg Novi, September 3-7, 2018. 2018;:74-75.
https://hdl.handle.net/21.15107/rcub_dais_3662 .

Ignjatović, Nenad, Sakač, Marija, Kuzminac, Ivana, Kojić, Vesna V., Marković, Smilja, Wu, Victoria, Uskoković, Vuk, Uskoković, Dragan, "Cell-selective toxicity of hydroxyapatite-chitosan oligosaccharide lactate particles loaded with a steroid cancer inhibitor" in Programme and The Book of Abstracts / Twentieth Annual Conference YUCOMAT 2018, Herceg Novi, September 3-7, 2018 (2018):74-75,
https://hdl.handle.net/21.15107/rcub_dais_3662 .

TY  - JOUR
AU  - Uskoković, Vuk
AU  - Marković, Smilja
AU  - Veselinović, Ljiljana
AU  - Škapin, Srečo Davor
AU  - Ignjatović, Nenad
AU  - Uskoković, Dragan
PY  - 2018
UR  - https://dais.sanu.ac.rs/123456789/4514
AB  - Transformations between amorphous and crystalline apatite mechanistically govern some of the most essential processes in bone metabolism, including biomineralization and bone remodeling. Fundamental understanding of this phase transition can help us gain control over the formation and dissolution of boney tissues in vivo and utilize that knowledge for various therapeutic ends. Crystallization of hydroxyapatite (HAp) and two tricalcium phosphate (TCP) polymorphs from the metastable precursor, amorphous calcium phosphate (ACP) was here studied kinetically and mechanistically using thermal analyses, X-ray diffraction and Fourier-transform infrared spectroscopy. Crystallization was detected in the differential thermal analysis as the exothermic peak at 639.5 °C at the slowest heating regimen of 5 °C min−1, while a combination of different kinetics models, including Augis–Bennett, Borchardt–Daniels, Johnson–Mehl–Avrami, Kissinger, Ozawa and Piloyan, yielded activation energies in the 435–450 kJ mol−1 range. Dehydrated ACP required a significant energy input to transform to HAp, thus indirectly proving the key role that structural water plays in this process in a biological setting. The phase transformation at high temperatures involved preformed nuclei and was solely due to their 3D growth, contrasting the edge-controlled nucleation derived earlier as the mechanism of growth in the solution. Crystallization was in both cases accompanied by the formation of needle-shape crystals of HAp through aggregation of ultrafine spherical units of ACP. Relationship between crystallinity and the heating rate was detected only for the initially amorphous structure, indicating a more intense and coherent lattice ordering process in annealed ACP than in HAp. Despite that, crystallization disobeyed the rule of inverse proportionality between the thermal energy required for the relaxation of defects and the level of strain, as the recovery rate of the initially poorly crystalline HAp was higher than that of ACP.
PB  - Royal Society of Chemistry (RSC)
T2  - Physical Chemistry Chemical Physics
T1  - Insights into the kinetics of thermally induced crystallization of amorphous calcium phosphate
SP  - 29221
EP  - 29235
VL  - 20
DO  - 10.1039/C8CP06460A
UR  - https://hdl.handle.net/21.15107/rcub_dais_4514
ER  - 

@article{
author = "Uskoković, Vuk and Marković, Smilja and Veselinović, Ljiljana and Škapin, Srečo Davor and Ignjatović, Nenad and Uskoković, Dragan",
year = "2018",
abstract = "Transformations between amorphous and crystalline apatite mechanistically govern some of the most essential processes in bone metabolism, including biomineralization and bone remodeling. Fundamental understanding of this phase transition can help us gain control over the formation and dissolution of boney tissues in vivo and utilize that knowledge for various therapeutic ends. Crystallization of hydroxyapatite (HAp) and two tricalcium phosphate (TCP) polymorphs from the metastable precursor, amorphous calcium phosphate (ACP) was here studied kinetically and mechanistically using thermal analyses, X-ray diffraction and Fourier-transform infrared spectroscopy. Crystallization was detected in the differential thermal analysis as the exothermic peak at 639.5 °C at the slowest heating regimen of 5 °C min−1, while a combination of different kinetics models, including Augis–Bennett, Borchardt–Daniels, Johnson–Mehl–Avrami, Kissinger, Ozawa and Piloyan, yielded activation energies in the 435–450 kJ mol−1 range. Dehydrated ACP required a significant energy input to transform to HAp, thus indirectly proving the key role that structural water plays in this process in a biological setting. The phase transformation at high temperatures involved preformed nuclei and was solely due to their 3D growth, contrasting the edge-controlled nucleation derived earlier as the mechanism of growth in the solution. Crystallization was in both cases accompanied by the formation of needle-shape crystals of HAp through aggregation of ultrafine spherical units of ACP. Relationship between crystallinity and the heating rate was detected only for the initially amorphous structure, indicating a more intense and coherent lattice ordering process in annealed ACP than in HAp. Despite that, crystallization disobeyed the rule of inverse proportionality between the thermal energy required for the relaxation of defects and the level of strain, as the recovery rate of the initially poorly crystalline HAp was higher than that of ACP.",
publisher = "Royal Society of Chemistry (RSC)",
journal = "Physical Chemistry Chemical Physics",
title = "Insights into the kinetics of thermally induced crystallization of amorphous calcium phosphate",
pages = "29221-29235",
volume = "20",
doi = "10.1039/C8CP06460A",
url = "https://hdl.handle.net/21.15107/rcub_dais_4514"
}

Uskoković, V., Marković, S., Veselinović, L., Škapin, S. D., Ignjatović, N.,& Uskoković, D.. (2018). Insights into the kinetics of thermally induced crystallization of amorphous calcium phosphate. in Physical Chemistry Chemical Physics
Royal Society of Chemistry (RSC)., 20, 29221-29235.
https://doi.org/10.1039/C8CP06460A
https://hdl.handle.net/21.15107/rcub_dais_4514

Uskoković V, Marković S, Veselinović L, Škapin SD, Ignjatović N, Uskoković D. Insights into the kinetics of thermally induced crystallization of amorphous calcium phosphate. in Physical Chemistry Chemical Physics. 2018;20:29221-29235.
doi:10.1039/C8CP06460A
https://hdl.handle.net/21.15107/rcub_dais_4514 .

Uskoković, Vuk, Marković, Smilja, Veselinović, Ljiljana, Škapin, Srečo Davor, Ignjatović, Nenad, Uskoković, Dragan, "Insights into the kinetics of thermally induced crystallization of amorphous calcium phosphate" in Physical Chemistry Chemical Physics, 20 (2018):29221-29235,
https://doi.org/10.1039/C8CP06460A .,
https://hdl.handle.net/21.15107/rcub_dais_4514 .

TY  - JOUR
AU  - Uskoković, Vuk
AU  - Marković, Smilja
AU  - Veselinović, Ljiljana
AU  - Škapin, Srečo Davor
AU  - Ignjatović, Nenad
AU  - Uskoković, Dragan
PY  - 2018
UR  - https://dais.sanu.ac.rs/123456789/4514
UR  - https://dais.sanu.ac.rs/123456789/4554
AB  - Transformations between amorphous and crystalline apatite mechanistically govern some of the most essential processes in bone metabolism, including biomineralization and bone remodeling. Fundamental understanding of this phase transition can help us gain control over the formation and dissolution of boney tissues in vivo and utilize that knowledge for various therapeutic ends. Crystallization of hydroxyapatite (HAp) and two tricalcium phosphate (TCP) polymorphs from the metastable precursor, amorphous calcium phosphate (ACP) was here studied kinetically and mechanistically using thermal analyses, X-ray diffraction and Fourier-transform infrared spectroscopy. Crystallization was detected in the differential thermal analysis as the exothermic peak at 639.5 °C at the slowest heating regimen of 5 °C min−1, while a combination of different kinetics models, including Augis–Bennett, Borchardt–Daniels, Johnson–Mehl–Avrami, Kissinger, Ozawa and Piloyan, yielded activation energies in the 435–450 kJ mol−1 range. Dehydrated ACP required a significant energy input to transform to HAp, thus indirectly proving the key role that structural water plays in this process in a biological setting. The phase transformation at high temperatures involved preformed nuclei and was solely due to their 3D growth, contrasting the edge-controlled nucleation derived earlier as the mechanism of growth in the solution. Crystallization was in both cases accompanied by the formation of needle-shape crystals of HAp through aggregation of ultrafine spherical units of ACP. Relationship between crystallinity and the heating rate was detected only for the initially amorphous structure, indicating a more intense and coherent lattice ordering process in annealed ACP than in HAp. Despite that, crystallization disobeyed the rule of inverse proportionality between the thermal energy required for the relaxation of defects and the level of strain, as the recovery rate of the initially poorly crystalline HAp was higher than that of ACP.
PB  - Royal Society of Chemistry (RSC)
T2  - Physical Chemistry Chemical Physics
T1  - Insights into the kinetics of thermally induced crystallization of amorphous calcium phosphate
SP  - 29221
EP  - 29235
VL  - 20
DO  - 10.1039/C8CP06460A
UR  - https://hdl.handle.net/21.15107/rcub_dais_4554
ER  - 

@article{
author = "Uskoković, Vuk and Marković, Smilja and Veselinović, Ljiljana and Škapin, Srečo Davor and Ignjatović, Nenad and Uskoković, Dragan",
year = "2018",
abstract = "Transformations between amorphous and crystalline apatite mechanistically govern some of the most essential processes in bone metabolism, including biomineralization and bone remodeling. Fundamental understanding of this phase transition can help us gain control over the formation and dissolution of boney tissues in vivo and utilize that knowledge for various therapeutic ends. Crystallization of hydroxyapatite (HAp) and two tricalcium phosphate (TCP) polymorphs from the metastable precursor, amorphous calcium phosphate (ACP) was here studied kinetically and mechanistically using thermal analyses, X-ray diffraction and Fourier-transform infrared spectroscopy. Crystallization was detected in the differential thermal analysis as the exothermic peak at 639.5 °C at the slowest heating regimen of 5 °C min−1, while a combination of different kinetics models, including Augis–Bennett, Borchardt–Daniels, Johnson–Mehl–Avrami, Kissinger, Ozawa and Piloyan, yielded activation energies in the 435–450 kJ mol−1 range. Dehydrated ACP required a significant energy input to transform to HAp, thus indirectly proving the key role that structural water plays in this process in a biological setting. The phase transformation at high temperatures involved preformed nuclei and was solely due to their 3D growth, contrasting the edge-controlled nucleation derived earlier as the mechanism of growth in the solution. Crystallization was in both cases accompanied by the formation of needle-shape crystals of HAp through aggregation of ultrafine spherical units of ACP. Relationship between crystallinity and the heating rate was detected only for the initially amorphous structure, indicating a more intense and coherent lattice ordering process in annealed ACP than in HAp. Despite that, crystallization disobeyed the rule of inverse proportionality between the thermal energy required for the relaxation of defects and the level of strain, as the recovery rate of the initially poorly crystalline HAp was higher than that of ACP.",
publisher = "Royal Society of Chemistry (RSC)",
journal = "Physical Chemistry Chemical Physics",
title = "Insights into the kinetics of thermally induced crystallization of amorphous calcium phosphate",
pages = "29221-29235",
volume = "20",
doi = "10.1039/C8CP06460A",
url = "https://hdl.handle.net/21.15107/rcub_dais_4554"
}

Uskoković, V., Marković, S., Veselinović, L., Škapin, S. D., Ignjatović, N.,& Uskoković, D.. (2018). Insights into the kinetics of thermally induced crystallization of amorphous calcium phosphate. in Physical Chemistry Chemical Physics
Royal Society of Chemistry (RSC)., 20, 29221-29235.
https://doi.org/10.1039/C8CP06460A
https://hdl.handle.net/21.15107/rcub_dais_4554

Uskoković V, Marković S, Veselinović L, Škapin SD, Ignjatović N, Uskoković D. Insights into the kinetics of thermally induced crystallization of amorphous calcium phosphate. in Physical Chemistry Chemical Physics. 2018;20:29221-29235.
doi:10.1039/C8CP06460A
https://hdl.handle.net/21.15107/rcub_dais_4554 .

Uskoković, Vuk, Marković, Smilja, Veselinović, Ljiljana, Škapin, Srečo Davor, Ignjatović, Nenad, Uskoković, Dragan, "Insights into the kinetics of thermally induced crystallization of amorphous calcium phosphate" in Physical Chemistry Chemical Physics, 20 (2018):29221-29235,
https://doi.org/10.1039/C8CP06460A .,
https://hdl.handle.net/21.15107/rcub_dais_4554 .

TY  - JOUR
AU  - Ignjatović, Nenad
AU  - Penov Gaši, Katarina
AU  - Wu, Victoria
AU  - Ajduković, Jovana
AU  - Kojić, Vesna V.
AU  - Vasiljević Radović, Dana
AU  - Kuzmanović, Maja
AU  - Uskoković, Vuk
AU  - Uskoković, Dragan
PY  - 2016
UR  - https://dais.sanu.ac.rs/123456789/15974
AB  - In an earlier study we demonstrated that hydroxyapatite nanoparticles coated with chitosan-poly(d,l)-lactide-co-glycolide (HAp/Ch-PLGA) target lungs following their intravenous injection into mice. In this study we utilize an emulsification process and freeze drying to load the composite HAp/Ch-PLGA particles with 17β-hydroxy-17α-picolyl-androst-5-en-3β-yl-acetate (A), a chemotherapeutic derivative of androstane and a novel compound with a selective anticancer activity against lung cancer cells. 1H NMR and 13C NMR techniques confirmed the intact structure of the derivative A following its entrapment within HAp/Ch-PLGA particles. The thermogravimetric and differential thermal analyses coupled with mass spectrometry were used to assess the thermal degradation products and properties of A-loaded HAp/Ch-PLGA. The loading efficiency, as indicated by the comparison of enthalpies of phase transitions in pure A and A-loaded HAp/Ch-PLGA, equaled 7.47wt.%. The release of A from HAp/Ch-PLGA was sustained, neither exhibiting a burst release nor plateauing after three weeks. Atomic force microscopy and particle size distribution analyses were used to confirm that the particles were spherical with a uniform size distribution of d50=168nm. In vitro cytotoxicity testing of A-loaded HAp/Ch-PLGA using MTT and trypan blue dye exclusion assays demonstrated that the particles were cytotoxic to the A549 human lung carcinoma cell line (46±2%), while simultaneously preserving high viability (83±3%) of regular MRC5 human lung fibroblasts and causing no harm to primary mouse lung fibroblasts. In conclusion, composite A-loaded HAp/Ch-PLGA particles could be seen as promising drug delivery platforms for selective cancer therapies, targeting malignant cells for destruction, while having a significantly lesser cytotoxic effect on the healthy cells.
PB  - Elsevier
T2  - Colloids and Surfaces B: Biointerfaces
T1  - Selective anticancer activity of hydroxyapatite/chitosan-poly(d,l)-lactide-co-glycolide particles loaded with an androstane-based cancer inhibitor
SP  - 629
EP  - 639
VL  - 148
DO  - 10.1016/j.colsurfb.2016.09.041
UR  - https://hdl.handle.net/21.15107/rcub_dais_15974
ER  - 

@article{
author = "Ignjatović, Nenad and Penov Gaši, Katarina and Wu, Victoria and Ajduković, Jovana and Kojić, Vesna V. and Vasiljević Radović, Dana and Kuzmanović, Maja and Uskoković, Vuk and Uskoković, Dragan",
year = "2016",
abstract = "In an earlier study we demonstrated that hydroxyapatite nanoparticles coated with chitosan-poly(d,l)-lactide-co-glycolide (HAp/Ch-PLGA) target lungs following their intravenous injection into mice. In this study we utilize an emulsification process and freeze drying to load the composite HAp/Ch-PLGA particles with 17β-hydroxy-17α-picolyl-androst-5-en-3β-yl-acetate (A), a chemotherapeutic derivative of androstane and a novel compound with a selective anticancer activity against lung cancer cells. 1H NMR and 13C NMR techniques confirmed the intact structure of the derivative A following its entrapment within HAp/Ch-PLGA particles. The thermogravimetric and differential thermal analyses coupled with mass spectrometry were used to assess the thermal degradation products and properties of A-loaded HAp/Ch-PLGA. The loading efficiency, as indicated by the comparison of enthalpies of phase transitions in pure A and A-loaded HAp/Ch-PLGA, equaled 7.47wt.%. The release of A from HAp/Ch-PLGA was sustained, neither exhibiting a burst release nor plateauing after three weeks. Atomic force microscopy and particle size distribution analyses were used to confirm that the particles were spherical with a uniform size distribution of d50=168nm. In vitro cytotoxicity testing of A-loaded HAp/Ch-PLGA using MTT and trypan blue dye exclusion assays demonstrated that the particles were cytotoxic to the A549 human lung carcinoma cell line (46±2%), while simultaneously preserving high viability (83±3%) of regular MRC5 human lung fibroblasts and causing no harm to primary mouse lung fibroblasts. In conclusion, composite A-loaded HAp/Ch-PLGA particles could be seen as promising drug delivery platforms for selective cancer therapies, targeting malignant cells for destruction, while having a significantly lesser cytotoxic effect on the healthy cells.",
publisher = "Elsevier",
journal = "Colloids and Surfaces B: Biointerfaces",
title = "Selective anticancer activity of hydroxyapatite/chitosan-poly(d,l)-lactide-co-glycolide particles loaded with an androstane-based cancer inhibitor",
pages = "629-639",
volume = "148",
doi = "10.1016/j.colsurfb.2016.09.041",
url = "https://hdl.handle.net/21.15107/rcub_dais_15974"
}

Ignjatović, N., Penov Gaši, K., Wu, V., Ajduković, J., Kojić, V. V., Vasiljević Radović, D., Kuzmanović, M., Uskoković, V.,& Uskoković, D.. (2016). Selective anticancer activity of hydroxyapatite/chitosan-poly(d,l)-lactide-co-glycolide particles loaded with an androstane-based cancer inhibitor. in Colloids and Surfaces B: Biointerfaces
Elsevier., 148, 629-639.
https://doi.org/10.1016/j.colsurfb.2016.09.041
https://hdl.handle.net/21.15107/rcub_dais_15974

Ignjatović N, Penov Gaši K, Wu V, Ajduković J, Kojić VV, Vasiljević Radović D, Kuzmanović M, Uskoković V, Uskoković D. Selective anticancer activity of hydroxyapatite/chitosan-poly(d,l)-lactide-co-glycolide particles loaded with an androstane-based cancer inhibitor. in Colloids and Surfaces B: Biointerfaces. 2016;148:629-639.
doi:10.1016/j.colsurfb.2016.09.041
https://hdl.handle.net/21.15107/rcub_dais_15974 .

Ignjatović, Nenad, Penov Gaši, Katarina, Wu, Victoria, Ajduković, Jovana, Kojić, Vesna V., Vasiljević Radović, Dana, Kuzmanović, Maja, Uskoković, Vuk, Uskoković, Dragan, "Selective anticancer activity of hydroxyapatite/chitosan-poly(d,l)-lactide-co-glycolide particles loaded with an androstane-based cancer inhibitor" in Colloids and Surfaces B: Biointerfaces, 148 (2016):629-639,
https://doi.org/10.1016/j.colsurfb.2016.09.041 .,
https://hdl.handle.net/21.15107/rcub_dais_15974 .

TY  - JOUR
AU  - Ignjatović, Nenad
AU  - Penov Gaši, Katarina
AU  - Wu, Victoria
AU  - Ajduković, Jovana
AU  - Kojić, Vesna
AU  - Vasiljević Radović, Dana
AU  - Kuzmanović, Maja
AU  - Uskoković, Vuk
AU  - Uskoković, Dragan
PY  - 2016
UR  - https://dais.sanu.ac.rs/123456789/15984
AB  - In an earlier study we demonstrated that hydroxyapatite nanoparticles coated with chitosan-poly(d,l)-lactide-co-glycolide (HAp/Ch-PLGA) target lungs following their intravenous injection into mice. In this study we utilize an emulsification process and freeze drying to load the composite HAp/Ch-PLGA particles with 17β-hydroxy-17α-picolyl-androst-5-en-3β-yl-acetate (A), a chemotherapeutic derivative of androstane and a novel compound with a selective anticancer activity against lung cancer cells. 1H NMR and 13C NMR techniques confirmed the intact structure of the derivative A following its entrapment within HAp/Ch-PLGA particles. The thermogravimetric and differential thermal analyses coupled with mass spectrometry were used to assess the thermal degradation products and properties of A-loaded HAp/Ch-PLGA. The loading efficiency, as indicated by the comparison of enthalpies of phase transitions in pure A and A-loaded HAp/Ch-PLGA, equaled 7.47 wt.%. The release of A from HAp/Ch-PLGA was sustained, neither exhibiting a burst release nor plateauing after three weeks. Atomic force microscopy and particle size distribution analyses were used to confirm that the particles were spherical with a uniform size distribution of d50 = 168 nm. In vitro cytotoxicity testing of A-loaded HAp/Ch-PLGA using MTT and trypan blue dye exclusion assays demonstrated that the particles were cytotoxic to the A549 human lung carcinoma cell line (46 ± 2%), while simultaneously preserving high viability (83 ± 3%) of regular MRC5 human lung fibroblasts and causing no harm to primary mouse lung fibroblasts. In conclusion, composite A-loaded HAp/Ch-PLGA particles could be seen as promising drug delivery platforms for selective cancer therapies, targeting malignant cells for destruction, while having a significantly lesser cytotoxic effect on the healthy cells.
T2  - Colloids and Surfaces B: Biointerfaces
T1  - Selective anticancer activity of hydroxyapatite/chitosan-poly(D,L)-lactide-co-glycolide particles loaded with an androstane-based cancer inhibitor
SP  - 629
EP  - 639
VL  - 148
DO  - 10.1016/j.colsurfb.2016.09.041
UR  - https://hdl.handle.net/21.15107/rcub_dais_15984
ER  - 

@article{
author = "Ignjatović, Nenad and Penov Gaši, Katarina and Wu, Victoria and Ajduković, Jovana and Kojić, Vesna and Vasiljević Radović, Dana and Kuzmanović, Maja and Uskoković, Vuk and Uskoković, Dragan",
year = "2016",
abstract = "In an earlier study we demonstrated that hydroxyapatite nanoparticles coated with chitosan-poly(d,l)-lactide-co-glycolide (HAp/Ch-PLGA) target lungs following their intravenous injection into mice. In this study we utilize an emulsification process and freeze drying to load the composite HAp/Ch-PLGA particles with 17β-hydroxy-17α-picolyl-androst-5-en-3β-yl-acetate (A), a chemotherapeutic derivative of androstane and a novel compound with a selective anticancer activity against lung cancer cells. 1H NMR and 13C NMR techniques confirmed the intact structure of the derivative A following its entrapment within HAp/Ch-PLGA particles. The thermogravimetric and differential thermal analyses coupled with mass spectrometry were used to assess the thermal degradation products and properties of A-loaded HAp/Ch-PLGA. The loading efficiency, as indicated by the comparison of enthalpies of phase transitions in pure A and A-loaded HAp/Ch-PLGA, equaled 7.47 wt.%. The release of A from HAp/Ch-PLGA was sustained, neither exhibiting a burst release nor plateauing after three weeks. Atomic force microscopy and particle size distribution analyses were used to confirm that the particles were spherical with a uniform size distribution of d50 = 168 nm. In vitro cytotoxicity testing of A-loaded HAp/Ch-PLGA using MTT and trypan blue dye exclusion assays demonstrated that the particles were cytotoxic to the A549 human lung carcinoma cell line (46 ± 2%), while simultaneously preserving high viability (83 ± 3%) of regular MRC5 human lung fibroblasts and causing no harm to primary mouse lung fibroblasts. In conclusion, composite A-loaded HAp/Ch-PLGA particles could be seen as promising drug delivery platforms for selective cancer therapies, targeting malignant cells for destruction, while having a significantly lesser cytotoxic effect on the healthy cells.",
journal = "Colloids and Surfaces B: Biointerfaces",
title = "Selective anticancer activity of hydroxyapatite/chitosan-poly(D,L)-lactide-co-glycolide particles loaded with an androstane-based cancer inhibitor",
pages = "629-639",
volume = "148",
doi = "10.1016/j.colsurfb.2016.09.041",
url = "https://hdl.handle.net/21.15107/rcub_dais_15984"
}

Ignjatović, N., Penov Gaši, K., Wu, V., Ajduković, J., Kojić, V., Vasiljević Radović, D., Kuzmanović, M., Uskoković, V.,& Uskoković, D.. (2016). Selective anticancer activity of hydroxyapatite/chitosan-poly(D,L)-lactide-co-glycolide particles loaded with an androstane-based cancer inhibitor. in Colloids and Surfaces B: Biointerfaces, 148, 629-639.
https://doi.org/10.1016/j.colsurfb.2016.09.041
https://hdl.handle.net/21.15107/rcub_dais_15984

Ignjatović N, Penov Gaši K, Wu V, Ajduković J, Kojić V, Vasiljević Radović D, Kuzmanović M, Uskoković V, Uskoković D. Selective anticancer activity of hydroxyapatite/chitosan-poly(D,L)-lactide-co-glycolide particles loaded with an androstane-based cancer inhibitor. in Colloids and Surfaces B: Biointerfaces. 2016;148:629-639.
doi:10.1016/j.colsurfb.2016.09.041
https://hdl.handle.net/21.15107/rcub_dais_15984 .

Ignjatović, Nenad, Penov Gaši, Katarina, Wu, Victoria, Ajduković, Jovana, Kojić, Vesna, Vasiljević Radović, Dana, Kuzmanović, Maja, Uskoković, Vuk, Uskoković, Dragan, "Selective anticancer activity of hydroxyapatite/chitosan-poly(D,L)-lactide-co-glycolide particles loaded with an androstane-based cancer inhibitor" in Colloids and Surfaces B: Biointerfaces, 148 (2016):629-639,
https://doi.org/10.1016/j.colsurfb.2016.09.041 .,
https://hdl.handle.net/21.15107/rcub_dais_15984 .

TY  - JOUR
AU  - Ignjatović, Nenad
AU  - Wu, Victoria
AU  - Ajduković, Zorica
AU  - Mihajilov Krstev, Tatjana
AU  - Uskoković, Vuk
AU  - Uskoković, Dragan
PY  - 2016
UR  - https://dais.sanu.ac.rs/123456789/15983
AB  - Composite biomaterials comprising nanostructured hydroxyapatite (HAp) have an enormous potential for natural bone tissue reparation, filling and augmentation. Chitosan (Ch) as a naturally derived polymer has many physicochemical and biological properties that make it an attractive material for use in bone tissue engineering. On the other hand, poly-D,L-lactide-co-glycolide (PLGA) is a synthetic polymer with a long history of use in sustained drug delivery and tissue engineering. However, while chitosan can disrupt the cell membrane integrity and may induce blood thrombosis, PLGA releases acidic byproducts that may cause tissue inflammation and interfere with the healing process. One of the strategies to improve the biocompatibility of Ch and PLGA is to combine them with compounds that exhibit complementary properties. In this study we present the synthesis and characterization, as well as in vitro and in vivo analyses of a nanoparticulate form of HAp coated with two different polymeric systems: (a) Ch and (b) a Ch-PLGA polymer blend. Solvent/non-solvent precipitation and freeze-drying were used for synthesis and processing, respectively, whereas thermogravimetry coupled with mass spectrometry was used for phase identification purposes in the coating process. HAp/Ch composite particles exhibited the highest antimicrobial activity against all four microbial strains tested in this work, but after the reconstruction of the bone defect they also caused inflammatory reactions in the newly formed tissue where the defect had lain. Coating HAp with a polymeric blend composed of Ch and PLGA led to a decrease in the reactivity and antimicrobial activity of the composite particles, but also to an increase in the quality of the newly formed bone tissue in the reconstructed defect area.
T2  - Materials science & engineering. C, Materials for biological applications
T1  - Chitosan-PLGA polymer blends as coatings for hydroxyapatite nanoparticles and their effect on antimicrobial properties, osteoconductivity and regeneration of osseous tissues
SP  - 357
EP  - 364
VL  - 60
DO  - 10.1016/j.msec.2015.11.061
UR  - https://hdl.handle.net/21.15107/rcub_dais_15983
ER  - 

@article{
author = "Ignjatović, Nenad and Wu, Victoria and Ajduković, Zorica and Mihajilov Krstev, Tatjana and Uskoković, Vuk and Uskoković, Dragan",
year = "2016",
abstract = "Composite biomaterials comprising nanostructured hydroxyapatite (HAp) have an enormous potential for natural bone tissue reparation, filling and augmentation. Chitosan (Ch) as a naturally derived polymer has many physicochemical and biological properties that make it an attractive material for use in bone tissue engineering. On the other hand, poly-D,L-lactide-co-glycolide (PLGA) is a synthetic polymer with a long history of use in sustained drug delivery and tissue engineering. However, while chitosan can disrupt the cell membrane integrity and may induce blood thrombosis, PLGA releases acidic byproducts that may cause tissue inflammation and interfere with the healing process. One of the strategies to improve the biocompatibility of Ch and PLGA is to combine them with compounds that exhibit complementary properties. In this study we present the synthesis and characterization, as well as in vitro and in vivo analyses of a nanoparticulate form of HAp coated with two different polymeric systems: (a) Ch and (b) a Ch-PLGA polymer blend. Solvent/non-solvent precipitation and freeze-drying were used for synthesis and processing, respectively, whereas thermogravimetry coupled with mass spectrometry was used for phase identification purposes in the coating process. HAp/Ch composite particles exhibited the highest antimicrobial activity against all four microbial strains tested in this work, but after the reconstruction of the bone defect they also caused inflammatory reactions in the newly formed tissue where the defect had lain. Coating HAp with a polymeric blend composed of Ch and PLGA led to a decrease in the reactivity and antimicrobial activity of the composite particles, but also to an increase in the quality of the newly formed bone tissue in the reconstructed defect area.",
journal = "Materials science & engineering. C, Materials for biological applications",
title = "Chitosan-PLGA polymer blends as coatings for hydroxyapatite nanoparticles and their effect on antimicrobial properties, osteoconductivity and regeneration of osseous tissues",
pages = "357-364",
volume = "60",
doi = "10.1016/j.msec.2015.11.061",
url = "https://hdl.handle.net/21.15107/rcub_dais_15983"
}

Ignjatović, N., Wu, V., Ajduković, Z., Mihajilov Krstev, T., Uskoković, V.,& Uskoković, D.. (2016). Chitosan-PLGA polymer blends as coatings for hydroxyapatite nanoparticles and their effect on antimicrobial properties, osteoconductivity and regeneration of osseous tissues. in Materials science & engineering. C, Materials for biological applications, 60, 357-364.
https://doi.org/10.1016/j.msec.2015.11.061
https://hdl.handle.net/21.15107/rcub_dais_15983

Ignjatović N, Wu V, Ajduković Z, Mihajilov Krstev T, Uskoković V, Uskoković D. Chitosan-PLGA polymer blends as coatings for hydroxyapatite nanoparticles and their effect on antimicrobial properties, osteoconductivity and regeneration of osseous tissues. in Materials science & engineering. C, Materials for biological applications. 2016;60:357-364.
doi:10.1016/j.msec.2015.11.061
https://hdl.handle.net/21.15107/rcub_dais_15983 .

Ignjatović, Nenad, Wu, Victoria, Ajduković, Zorica, Mihajilov Krstev, Tatjana, Uskoković, Vuk, Uskoković, Dragan, "Chitosan-PLGA polymer blends as coatings for hydroxyapatite nanoparticles and their effect on antimicrobial properties, osteoconductivity and regeneration of osseous tissues" in Materials science & engineering. C, Materials for biological applications, 60 (2016):357-364,
https://doi.org/10.1016/j.msec.2015.11.061 .,
https://hdl.handle.net/21.15107/rcub_dais_15983 .

TY  - JOUR
AU  - Ignjatović, Nenad
AU  - Wu, Victoria
AU  - Ajduković, Zorica
AU  - Mihajilov Krstev, Tatjana
AU  - Uskoković, Vuk
AU  - Uskoković, Dragan
PY  - 2016
UR  - https://dais.sanu.ac.rs/123456789/15975
AB  - Composite biomaterials comprising nanostructured hydroxyapatite (HAp) have an enormous potential for natural bone tissue reparation, filling and augmentation. Chitosan (Ch) as a naturally derived polymer has many physicochemical and biological properties that make it an attractive material for use in bone tissue engineering. On the other hand, poly-D,L-lactide-co-glycolide (PLGA) is a synthetic polymer with a long history of use in sustained drug delivery and tissue engineering. However, while chitosan can disrupt the cell membrane integrity and may induce blood thrombosis, PLGA releases acidic byproducts that may cause tissue inflammation and interfere with the healing process. One of the strategies to improve the biocompatibility of Ch and PLGA is to combine them with compounds that exhibit complementary properties. In this study we present the synthesis and characterization, as well as in vitro and in vivo analyses of a nanoparticulate form of HAp coated with two different polymeric systems: (a) Ch and (b) a Ch-PLGA polymer blend. Solvent/non-solvent precipitation and freeze-drying were used for synthesis and processing, respectively, whereas thermogravimetry coupled with mass spectrometry was used for phase identification purposes in the coating process. HAp/Ch composite particles exhibited the highest antimicrobial activity against all four microbial strains tested in this work, but after the reconstruction of the bone defect they also caused inflammatory reactions in the newly formed tissue where the defect had lain. Coating HAp with a polymeric blend composed of Ch and PLGA led to a decrease in the reactivity and antimicrobial activity of the composite particles, but also to an increase in the quality of the newly formed bone tissue in the reconstructed defect area.
PB  - Elsevier
T2  - Materials Science and Engineering C
T1  - Chitosan-PLGA polymer blends as coatings for hydroxyapatite nanoparticles and their effect on antimicrobial properties, osteoconductivity and regeneration of osseous tissues
SP  - 357
EP  - 364
VL  - 60
DO  - 10.1016/j.msec.2015.11.061
UR  - https://hdl.handle.net/21.15107/rcub_dais_15975
ER  - 

@article{
author = "Ignjatović, Nenad and Wu, Victoria and Ajduković, Zorica and Mihajilov Krstev, Tatjana and Uskoković, Vuk and Uskoković, Dragan",
year = "2016",
abstract = "Composite biomaterials comprising nanostructured hydroxyapatite (HAp) have an enormous potential for natural bone tissue reparation, filling and augmentation. Chitosan (Ch) as a naturally derived polymer has many physicochemical and biological properties that make it an attractive material for use in bone tissue engineering. On the other hand, poly-D,L-lactide-co-glycolide (PLGA) is a synthetic polymer with a long history of use in sustained drug delivery and tissue engineering. However, while chitosan can disrupt the cell membrane integrity and may induce blood thrombosis, PLGA releases acidic byproducts that may cause tissue inflammation and interfere with the healing process. One of the strategies to improve the biocompatibility of Ch and PLGA is to combine them with compounds that exhibit complementary properties. In this study we present the synthesis and characterization, as well as in vitro and in vivo analyses of a nanoparticulate form of HAp coated with two different polymeric systems: (a) Ch and (b) a Ch-PLGA polymer blend. Solvent/non-solvent precipitation and freeze-drying were used for synthesis and processing, respectively, whereas thermogravimetry coupled with mass spectrometry was used for phase identification purposes in the coating process. HAp/Ch composite particles exhibited the highest antimicrobial activity against all four microbial strains tested in this work, but after the reconstruction of the bone defect they also caused inflammatory reactions in the newly formed tissue where the defect had lain. Coating HAp with a polymeric blend composed of Ch and PLGA led to a decrease in the reactivity and antimicrobial activity of the composite particles, but also to an increase in the quality of the newly formed bone tissue in the reconstructed defect area.",
publisher = "Elsevier",
journal = "Materials Science and Engineering C",
title = "Chitosan-PLGA polymer blends as coatings for hydroxyapatite nanoparticles and their effect on antimicrobial properties, osteoconductivity and regeneration of osseous tissues",
pages = "357-364",
volume = "60",
doi = "10.1016/j.msec.2015.11.061",
url = "https://hdl.handle.net/21.15107/rcub_dais_15975"
}

Ignjatović, N., Wu, V., Ajduković, Z., Mihajilov Krstev, T., Uskoković, V.,& Uskoković, D.. (2016). Chitosan-PLGA polymer blends as coatings for hydroxyapatite nanoparticles and their effect on antimicrobial properties, osteoconductivity and regeneration of osseous tissues. in Materials Science and Engineering C
Elsevier., 60, 357-364.
https://doi.org/10.1016/j.msec.2015.11.061
https://hdl.handle.net/21.15107/rcub_dais_15975

Ignjatović N, Wu V, Ajduković Z, Mihajilov Krstev T, Uskoković V, Uskoković D. Chitosan-PLGA polymer blends as coatings for hydroxyapatite nanoparticles and their effect on antimicrobial properties, osteoconductivity and regeneration of osseous tissues. in Materials Science and Engineering C. 2016;60:357-364.
doi:10.1016/j.msec.2015.11.061
https://hdl.handle.net/21.15107/rcub_dais_15975 .

Ignjatović, Nenad, Wu, Victoria, Ajduković, Zorica, Mihajilov Krstev, Tatjana, Uskoković, Vuk, Uskoković, Dragan, "Chitosan-PLGA polymer blends as coatings for hydroxyapatite nanoparticles and their effect on antimicrobial properties, osteoconductivity and regeneration of osseous tissues" in Materials Science and Engineering C, 60 (2016):357-364,
https://doi.org/10.1016/j.msec.2015.11.061 .,
https://hdl.handle.net/21.15107/rcub_dais_15975 .

TY  - CONF
AU  - Ignjatović, Nenad
AU  - Penov Gaši, Katarina
AU  - Wu, Victoria
AU  - Ajduković, Jovana
AU  - Kojić, Vesna
AU  - Vasiljević Radović, Dana
AU  - Uskoković, Vuk
AU  - Uskoković, Dragan
PY  - 2016
UR  - https://dais.sanu.ac.rs/123456789/896
AB  - The applicative potential of synthetic calcium phosphates, especially hydroxyapatite (HAp), has become intensely broadened in the past 10 years, from bone tissue engineering to multiple other fields of biomedicine. Previously we have shown that hydroxyapatite nanoparticles coated with chitosan-poly(D,L)-lactide-co-glycolide (HAp/Ch-PLGA) target lungs following their intravenous administration into mice. For this purpose radioactive 125-Iodine (125I), a low energy gamma emitter, was used to develop a novel in situ method for radiolabeling of particles and investigation of their biodistribution. In this study we utilize an emulsification process and freeze drying to load the composite particles based on hydroxyapatite nanocarrier, chitosane and poly(lactic-co-glycolic acid) with 17β- hydroxy-17α-picolyl-androst-5-en-3β-acetate (A), a chemotherapeutic derivative of androstane. The picolyl androstane derivatives showed high potency in the cell inhibitors of hormonedependent cancers (adenocarcinoma, prostate cancer, cervix carcinoma, colon cancer, etc.). 1H NMR, 13C NMR and high-resolution time-of-flight mass spectrometry (MS) techniques confirmed the intact structure of the derivative A following its entrapment within HAp/Ch-PLGA particles. The synthesized particles of A-loaded HAp/Ch-PLGA were found to be spherical in shape with a uniform size distribution of d50=168 nm. The release of A from HAp/Ch-PLGA was sustained, with no burst release or plateauing after three weeks. The obtained results of the DET and MTT tests show that the particles of A-loaded HAp/Ch-PLGA exhibit almost three times higher cytotoxicity towards lung adenocarcinoma cells (A549) than towards healthy cells (MRC5), while at the same time allowing twice as fast recovery of healthy cells. We have also analyzed the period of recovery of healthy, as well as cancer cells, following the treatment with A-loaded HAp/Ch-PLGA. After treatment with A-loaded HAp/Ch-PLGA, healthy cells recover twice as fast as the malignant ones. Immunofluorescent staining of primary fibroblasts interacting with HAp/Ch-PLGA and A-HAp/Ch-PLGA particles demonstrates no negative morphological or proliferative effects on cells.
PB  - Belgrade : Materials Research Society of Serbia
C3  - Programme and The Book of Abstracts / Eighteenth Annual Conference YUCOMAT 2016, Herceg Novi, September 5-10, 2016
T1  - Tumor-selective hybrid system based on hydroxyapatite nanocarrier, chitosan, poly(lactic-co-glycolic acid) and androstan derivate
SP  - 27
EP  - 27
UR  - https://hdl.handle.net/21.15107/rcub_dais_896
ER  - 

@conference{
author = "Ignjatović, Nenad and Penov Gaši, Katarina and Wu, Victoria and Ajduković, Jovana and Kojić, Vesna and Vasiljević Radović, Dana and Uskoković, Vuk and Uskoković, Dragan",
year = "2016",
abstract = "The applicative potential of synthetic calcium phosphates, especially hydroxyapatite (HAp), has become intensely broadened in the past 10 years, from bone tissue engineering to multiple other fields of biomedicine. Previously we have shown that hydroxyapatite nanoparticles coated with chitosan-poly(D,L)-lactide-co-glycolide (HAp/Ch-PLGA) target lungs following their intravenous administration into mice. For this purpose radioactive 125-Iodine (125I), a low energy gamma emitter, was used to develop a novel in situ method for radiolabeling of particles and investigation of their biodistribution. In this study we utilize an emulsification process and freeze drying to load the composite particles based on hydroxyapatite nanocarrier, chitosane and poly(lactic-co-glycolic acid) with 17β- hydroxy-17α-picolyl-androst-5-en-3β-acetate (A), a chemotherapeutic derivative of androstane. The picolyl androstane derivatives showed high potency in the cell inhibitors of hormonedependent cancers (adenocarcinoma, prostate cancer, cervix carcinoma, colon cancer, etc.). 1H NMR, 13C NMR and high-resolution time-of-flight mass spectrometry (MS) techniques confirmed the intact structure of the derivative A following its entrapment within HAp/Ch-PLGA particles. The synthesized particles of A-loaded HAp/Ch-PLGA were found to be spherical in shape with a uniform size distribution of d50=168 nm. The release of A from HAp/Ch-PLGA was sustained, with no burst release or plateauing after three weeks. The obtained results of the DET and MTT tests show that the particles of A-loaded HAp/Ch-PLGA exhibit almost three times higher cytotoxicity towards lung adenocarcinoma cells (A549) than towards healthy cells (MRC5), while at the same time allowing twice as fast recovery of healthy cells. We have also analyzed the period of recovery of healthy, as well as cancer cells, following the treatment with A-loaded HAp/Ch-PLGA. After treatment with A-loaded HAp/Ch-PLGA, healthy cells recover twice as fast as the malignant ones. Immunofluorescent staining of primary fibroblasts interacting with HAp/Ch-PLGA and A-HAp/Ch-PLGA particles demonstrates no negative morphological or proliferative effects on cells.",
publisher = "Belgrade : Materials Research Society of Serbia",
journal = "Programme and The Book of Abstracts / Eighteenth Annual Conference YUCOMAT 2016, Herceg Novi, September 5-10, 2016",
title = "Tumor-selective hybrid system based on hydroxyapatite nanocarrier, chitosan, poly(lactic-co-glycolic acid) and androstan derivate",
pages = "27-27",
url = "https://hdl.handle.net/21.15107/rcub_dais_896"
}

Ignjatović, N., Penov Gaši, K., Wu, V., Ajduković, J., Kojić, V., Vasiljević Radović, D., Uskoković, V.,& Uskoković, D.. (2016). Tumor-selective hybrid system based on hydroxyapatite nanocarrier, chitosan, poly(lactic-co-glycolic acid) and androstan derivate. in Programme and The Book of Abstracts / Eighteenth Annual Conference YUCOMAT 2016, Herceg Novi, September 5-10, 2016
Belgrade : Materials Research Society of Serbia., 27-27.
https://hdl.handle.net/21.15107/rcub_dais_896

Ignjatović N, Penov Gaši K, Wu V, Ajduković J, Kojić V, Vasiljević Radović D, Uskoković V, Uskoković D. Tumor-selective hybrid system based on hydroxyapatite nanocarrier, chitosan, poly(lactic-co-glycolic acid) and androstan derivate. in Programme and The Book of Abstracts / Eighteenth Annual Conference YUCOMAT 2016, Herceg Novi, September 5-10, 2016. 2016;:27-27.
https://hdl.handle.net/21.15107/rcub_dais_896 .

Ignjatović, Nenad, Penov Gaši, Katarina, Wu, Victoria, Ajduković, Jovana, Kojić, Vesna, Vasiljević Radović, Dana, Uskoković, Vuk, Uskoković, Dragan, "Tumor-selective hybrid system based on hydroxyapatite nanocarrier, chitosan, poly(lactic-co-glycolic acid) and androstan derivate" in Programme and The Book of Abstracts / Eighteenth Annual Conference YUCOMAT 2016, Herceg Novi, September 5-10, 2016 (2016):27-27,
https://hdl.handle.net/21.15107/rcub_dais_896 .

TY  - JOUR
AU  - Stojanović, Zoran S.
AU  - Ignjatović, Nenad
AU  - Wu, Victoria
AU  - Žunič, Vojka
AU  - Veselinović, Ljiljana
AU  - Škapin, Srečo Davor
AU  - Miljković, Miroslav
AU  - Uskoković, Vuk
AU  - Uskoković, Dragan
PY  - 2016
UR  - https://dais.sanu.ac.rs/123456789/16006
AB  - Recent developments in bone tissue engineering have led to an increased interest in one-dimensional (1D) hydroxyapatite (HA) nano- and micro-structures such as wires, ribbons and tubes. They have been proposed for use as cell substrates, reinforcing phases in composites and carriers for biologically active substances. Here we demonstrate the synthesis of 1D HA structures using an optimized, urea-assisted, high-yield hydrothermal batch process. The one-pot process, yielding HA structures composed of bundles of ribbons and wires, was typified by the simultaneous occurrence of a multitude of intermediate reactions, failing to meet the uniformity criteria over particle morphology and size. To overcome these issues, the preparation procedure was divided to two stages: dicalcium phosphate platelets synthesized in the first step were used as a precursor for the synthesis of 1D HA in the second stage. Despite the elongated particle morphologies, both the precursor and the final product exhibited excellent biocompatibility and caused no reduction of viability when tested against osteoblastic MC3T3-E1 cells in 2D culture up to the concentration of 2.6 mg/cm2. X-ray powder diffraction combined with a range of electron microscopies and laser diffraction analyses was used to elucidate the formation mechanism and the microstructure of the final particles. The two-step synthesis involved a more direct transformation of DCP to 1D HA with the average diameter of 37 nm and the aspect ratio exceeding 100:1. The comparison of crystalline domain sizes along different crystallographic directions showed no signs of significant anisotropy, while indicating that individual nanowires are ordered in bundles in the b crystallographic direction of the P63/m space group of HA. Intermediate processes, e.g., dehydration of dicalcium phosphate, are critical for the formation of 1D HA alongside other key aspects of this phase transformation, it must be investigated in more detail in the continuous design of smart HA micro- and nano-structures with advanced therapeutic potentials.
PB  - Elsevier
T2  - Materials Science and Engineering: C
T1  - Hydrothermally processed 1D hydroxyapatite: Mechanism of formation and biocompatibility studies
SP  - 746
EP  - 757
VL  - 68
DO  - 10.1016/j.msec.2016.06.047
UR  - https://hdl.handle.net/21.15107/rcub_dais_16006
ER  - 

@article{
author = "Stojanović, Zoran S. and Ignjatović, Nenad and Wu, Victoria and Žunič, Vojka and Veselinović, Ljiljana and Škapin, Srečo Davor and Miljković, Miroslav and Uskoković, Vuk and Uskoković, Dragan",
year = "2016",
abstract = "Recent developments in bone tissue engineering have led to an increased interest in one-dimensional (1D) hydroxyapatite (HA) nano- and micro-structures such as wires, ribbons and tubes. They have been proposed for use as cell substrates, reinforcing phases in composites and carriers for biologically active substances. Here we demonstrate the synthesis of 1D HA structures using an optimized, urea-assisted, high-yield hydrothermal batch process. The one-pot process, yielding HA structures composed of bundles of ribbons and wires, was typified by the simultaneous occurrence of a multitude of intermediate reactions, failing to meet the uniformity criteria over particle morphology and size. To overcome these issues, the preparation procedure was divided to two stages: dicalcium phosphate platelets synthesized in the first step were used as a precursor for the synthesis of 1D HA in the second stage. Despite the elongated particle morphologies, both the precursor and the final product exhibited excellent biocompatibility and caused no reduction of viability when tested against osteoblastic MC3T3-E1 cells in 2D culture up to the concentration of 2.6 mg/cm2. X-ray powder diffraction combined with a range of electron microscopies and laser diffraction analyses was used to elucidate the formation mechanism and the microstructure of the final particles. The two-step synthesis involved a more direct transformation of DCP to 1D HA with the average diameter of 37 nm and the aspect ratio exceeding 100:1. The comparison of crystalline domain sizes along different crystallographic directions showed no signs of significant anisotropy, while indicating that individual nanowires are ordered in bundles in the b crystallographic direction of the P63/m space group of HA. Intermediate processes, e.g., dehydration of dicalcium phosphate, are critical for the formation of 1D HA alongside other key aspects of this phase transformation, it must be investigated in more detail in the continuous design of smart HA micro- and nano-structures with advanced therapeutic potentials.",
publisher = "Elsevier",
journal = "Materials Science and Engineering: C",
title = "Hydrothermally processed 1D hydroxyapatite: Mechanism of formation and biocompatibility studies",
pages = "746-757",
volume = "68",
doi = "10.1016/j.msec.2016.06.047",
url = "https://hdl.handle.net/21.15107/rcub_dais_16006"
}

Stojanović, Z. S., Ignjatović, N., Wu, V., Žunič, V., Veselinović, L., Škapin, S. D., Miljković, M., Uskoković, V.,& Uskoković, D.. (2016). Hydrothermally processed 1D hydroxyapatite: Mechanism of formation and biocompatibility studies. in Materials Science and Engineering: C
Elsevier., 68, 746-757.
https://doi.org/10.1016/j.msec.2016.06.047
https://hdl.handle.net/21.15107/rcub_dais_16006

Stojanović ZS, Ignjatović N, Wu V, Žunič V, Veselinović L, Škapin SD, Miljković M, Uskoković V, Uskoković D. Hydrothermally processed 1D hydroxyapatite: Mechanism of formation and biocompatibility studies. in Materials Science and Engineering: C. 2016;68:746-757.
doi:10.1016/j.msec.2016.06.047
https://hdl.handle.net/21.15107/rcub_dais_16006 .

Stojanović, Zoran S., Ignjatović, Nenad, Wu, Victoria, Žunič, Vojka, Veselinović, Ljiljana, Škapin, Srečo Davor, Miljković, Miroslav, Uskoković, Vuk, Uskoković, Dragan, "Hydrothermally processed 1D hydroxyapatite: Mechanism of formation and biocompatibility studies" in Materials Science and Engineering: C, 68 (2016):746-757,
https://doi.org/10.1016/j.msec.2016.06.047 .,
https://hdl.handle.net/21.15107/rcub_dais_16006 .

TY  - JOUR
AU  - Stojanović, Zoran S.
AU  - Ignjatović, Nenad
AU  - Wu, Victoria
AU  - Žunič, Vojka
AU  - Veselinović, Ljiljana
AU  - Škapin, Srečo Davor
AU  - Miljković, Miroslav
AU  - Uskoković, Vuk
AU  - Uskoković, Dragan
PY  - 2016
UR  - https://dais.sanu.ac.rs/123456789/15985
AB  - Recent developments in bone tissue engineering have led to an increased interest in one-dimensional (1D) hydroxyapatite (HA) nano- and micro-structures such as wires, ribbons and tubes. They have been proposed for use as cell substrates, reinforcing phases in composites and carriers for biologically active substances. Here we demonstrate the synthesis of 1D HA structures using an optimized, urea-assisted, high-yield hydrothermal batch process. The one-pot process, yielding HA structures composed of bundles of ribbons and wires, was typified by the simultaneous occurrence of a multitude of intermediate reactions, failing to meet the uniformity criteria over particle morphology and size. To overcome these issues, the preparation procedure was divided to two stages: dicalcium phosphate platelets synthesized in the first step were used as a precursor for the synthesis of 1D HA in the second stage. Despite the elongated particle morphologies, both the precursor and the final product exhibited excellent biocompatibility and caused no reduction of viability when tested against osteoblastic MC3T3-E1 cells in 2D culture up to the concentration of 2.6 mg/cm2. X-ray powder diffraction combined with a range of electron microscopies and laser diffraction analyses was used to elucidate the formation mechanism and the microstructure of the final particles. The two-step synthesis involved a more direct transformation of DCP to 1D HA with the average diameter of 37 nm and the aspect ratio exceeding 100:1. The comparison of crystalline domain sizes along different crystallographic directions showed no signs of significant anisotropy, while indicating that individual nanowires are ordered in bundles in the b crystallographic direction of the P63/m space group of HA. Intermediate processes, e.g., dehydration of dicalcium phosphate, are critical for the formation of 1D HA alongside other key aspects of this phase transformation, it must be investigated in more detail in the continuous design of smart HA micro- and nano-structures with advanced therapeutic potentials.
T2  - Materials Science and Engineering: C
T1  - Hydrothermally processed 1D hydroxyapatite: Mechanism of formation and biocompatibility studies
SP  - 746
EP  - 757
VL  - 68
DO  - 10.1016/j.msec.2016.06.047
UR  - https://hdl.handle.net/21.15107/rcub_dais_15985
ER  - 

@article{
author = "Stojanović, Zoran S. and Ignjatović, Nenad and Wu, Victoria and Žunič, Vojka and Veselinović, Ljiljana and Škapin, Srečo Davor and Miljković, Miroslav and Uskoković, Vuk and Uskoković, Dragan",
year = "2016",
abstract = "Recent developments in bone tissue engineering have led to an increased interest in one-dimensional (1D) hydroxyapatite (HA) nano- and micro-structures such as wires, ribbons and tubes. They have been proposed for use as cell substrates, reinforcing phases in composites and carriers for biologically active substances. Here we demonstrate the synthesis of 1D HA structures using an optimized, urea-assisted, high-yield hydrothermal batch process. The one-pot process, yielding HA structures composed of bundles of ribbons and wires, was typified by the simultaneous occurrence of a multitude of intermediate reactions, failing to meet the uniformity criteria over particle morphology and size. To overcome these issues, the preparation procedure was divided to two stages: dicalcium phosphate platelets synthesized in the first step were used as a precursor for the synthesis of 1D HA in the second stage. Despite the elongated particle morphologies, both the precursor and the final product exhibited excellent biocompatibility and caused no reduction of viability when tested against osteoblastic MC3T3-E1 cells in 2D culture up to the concentration of 2.6 mg/cm2. X-ray powder diffraction combined with a range of electron microscopies and laser diffraction analyses was used to elucidate the formation mechanism and the microstructure of the final particles. The two-step synthesis involved a more direct transformation of DCP to 1D HA with the average diameter of 37 nm and the aspect ratio exceeding 100:1. The comparison of crystalline domain sizes along different crystallographic directions showed no signs of significant anisotropy, while indicating that individual nanowires are ordered in bundles in the b crystallographic direction of the P63/m space group of HA. Intermediate processes, e.g., dehydration of dicalcium phosphate, are critical for the formation of 1D HA alongside other key aspects of this phase transformation, it must be investigated in more detail in the continuous design of smart HA micro- and nano-structures with advanced therapeutic potentials.",
journal = "Materials Science and Engineering: C",
title = "Hydrothermally processed 1D hydroxyapatite: Mechanism of formation and biocompatibility studies",
pages = "746-757",
volume = "68",
doi = "10.1016/j.msec.2016.06.047",
url = "https://hdl.handle.net/21.15107/rcub_dais_15985"
}

Stojanović, Z. S., Ignjatović, N., Wu, V., Žunič, V., Veselinović, L., Škapin, S. D., Miljković, M., Uskoković, V.,& Uskoković, D.. (2016). Hydrothermally processed 1D hydroxyapatite: Mechanism of formation and biocompatibility studies. in Materials Science and Engineering: C, 68, 746-757.
https://doi.org/10.1016/j.msec.2016.06.047
https://hdl.handle.net/21.15107/rcub_dais_15985

Stojanović ZS, Ignjatović N, Wu V, Žunič V, Veselinović L, Škapin SD, Miljković M, Uskoković V, Uskoković D. Hydrothermally processed 1D hydroxyapatite: Mechanism of formation and biocompatibility studies. in Materials Science and Engineering: C. 2016;68:746-757.
doi:10.1016/j.msec.2016.06.047
https://hdl.handle.net/21.15107/rcub_dais_15985 .

Stojanović, Zoran S., Ignjatović, Nenad, Wu, Victoria, Žunič, Vojka, Veselinović, Ljiljana, Škapin, Srečo Davor, Miljković, Miroslav, Uskoković, Vuk, Uskoković, Dragan, "Hydrothermally processed 1D hydroxyapatite: Mechanism of formation and biocompatibility studies" in Materials Science and Engineering: C, 68 (2016):746-757,
https://doi.org/10.1016/j.msec.2016.06.047 .,
https://hdl.handle.net/21.15107/rcub_dais_15985 .

TY  - CONF
AU  - Ignjatović, Nenad
AU  - Uskoković, Vuk
AU  - Ajduković, Zorica
AU  - Mihajilov Krstev, Tatjana
AU  - Uskoković, Dragan
PY  - 2015
UR  - https://dais.sanu.ac.rs/123456789/824
AB  - Composite biomaterials based on nano-hydroxyapatite have an enormous potential for natural bone tissue reparation, filling and augmentation. Multifunctional nanoparticulate systems based on HAp coated with biocompatible and bioresorbable polymers make a separate group of filler systems in bone tissue engineering [1,2]. Chitosan has many physicochemical (reactive OH and NH2 groups) and biological (biocompatible, biodegradable) properties that make it an attractive material for use in bone tissue engineering. However, chitosan may induce thrombosis and it is therefore unsuitable as blood – contacting biomaterial. One of the strategies to improve the biocompatibility of chitosan is combination of this biopolymer with compounds that exhibit complementary properties. 
In our studies, we present the synthesis, characterization, in vitro and in vivo research of a particulate form of nano HAp-coated polymer systems. We synthesized nanoparticulate HAp coated with chitosan (Ch) and a chitosan-poly-D,L-lactide-co-glycolide (Ch-PLGA) polymer blend obtained via the solvent/non-solvent method and freeze-drying processing. We also examined the possibility of using Thermo-Gravimetric Analysis/Differential-Thermal Analysis (DTA/TGA) coupled on-line with mass spectrometry (MS) as a finger print for identification purposes in coating processes. The quantitative antimicrobial test has shown that HAp/Ch-PLGA have some antibacterial properties (MIC (mg/mL): Pseudomonas aeruginosa – 6.40, Staphylococcus aureus – 6.40, Staphylococcus epidermidis – 3.20). MTT assay was used to test cytotoxicity and cell viability. By using HAp/Ch-PLGA in the form of a filler a high level of reparatory ability, with the presence Haversian canals and cement lines in reconstructed of bone defect, was achieved in vivo. 

[1] N. Ignjatovic, C. Liu, J. Czernuszka, D. Uskokovic, Micro and nano/injectable composite biomaterials containing calcium phosphate coated with poly(dl-lactide-co-glycolide), Acta Biomaterialia, 3 (2007) 927-935 
[2] N. Ignjatović, V. Uskoković, Z. Ajduković, D. Uskoković, Multifunctional hydroxyapatite and poly(D,L-lactide-co-glycolide) nanoparticles for the local delivery of cholecalciferol, Materials Science and Engineering: C 33 (2013) 943–950
C3  - ITNANO2015: 3RD International Translational Nanomedicine Conference  21-26. June. 2015, Milocer, Hotel Maestral, Montenegro: Book of abstracts
T1  - Rapid bone regeneration with nano-hydroxyapatite coated with a chitosan-poly (D, L)-lactide-co-glycolide bone-filling material with osteocondactive and antimicrobial properties
SP  - 15
EP  - 16
UR  - https://hdl.handle.net/21.15107/rcub_dais_824
ER  - 

@conference{
author = "Ignjatović, Nenad and Uskoković, Vuk and Ajduković, Zorica and Mihajilov Krstev, Tatjana and Uskoković, Dragan",
year = "2015",
abstract = "Composite biomaterials based on nano-hydroxyapatite have an enormous potential for natural bone tissue reparation, filling and augmentation. Multifunctional nanoparticulate systems based on HAp coated with biocompatible and bioresorbable polymers make a separate group of filler systems in bone tissue engineering [1,2]. Chitosan has many physicochemical (reactive OH and NH2 groups) and biological (biocompatible, biodegradable) properties that make it an attractive material for use in bone tissue engineering. However, chitosan may induce thrombosis and it is therefore unsuitable as blood – contacting biomaterial. One of the strategies to improve the biocompatibility of chitosan is combination of this biopolymer with compounds that exhibit complementary properties. 
In our studies, we present the synthesis, characterization, in vitro and in vivo research of a particulate form of nano HAp-coated polymer systems. We synthesized nanoparticulate HAp coated with chitosan (Ch) and a chitosan-poly-D,L-lactide-co-glycolide (Ch-PLGA) polymer blend obtained via the solvent/non-solvent method and freeze-drying processing. We also examined the possibility of using Thermo-Gravimetric Analysis/Differential-Thermal Analysis (DTA/TGA) coupled on-line with mass spectrometry (MS) as a finger print for identification purposes in coating processes. The quantitative antimicrobial test has shown that HAp/Ch-PLGA have some antibacterial properties (MIC (mg/mL): Pseudomonas aeruginosa – 6.40, Staphylococcus aureus – 6.40, Staphylococcus epidermidis – 3.20). MTT assay was used to test cytotoxicity and cell viability. By using HAp/Ch-PLGA in the form of a filler a high level of reparatory ability, with the presence Haversian canals and cement lines in reconstructed of bone defect, was achieved in vivo. 

[1] N. Ignjatovic, C. Liu, J. Czernuszka, D. Uskokovic, Micro and nano/injectable composite biomaterials containing calcium phosphate coated with poly(dl-lactide-co-glycolide), Acta Biomaterialia, 3 (2007) 927-935 
[2] N. Ignjatović, V. Uskoković, Z. Ajduković, D. Uskoković, Multifunctional hydroxyapatite and poly(D,L-lactide-co-glycolide) nanoparticles for the local delivery of cholecalciferol, Materials Science and Engineering: C 33 (2013) 943–950",
journal = "ITNANO2015: 3RD International Translational Nanomedicine Conference  21-26. June. 2015, Milocer, Hotel Maestral, Montenegro: Book of abstracts",
title = "Rapid bone regeneration with nano-hydroxyapatite coated with a chitosan-poly (D, L)-lactide-co-glycolide bone-filling material with osteocondactive and antimicrobial properties",
pages = "15-16",
url = "https://hdl.handle.net/21.15107/rcub_dais_824"
}

Ignjatović, N., Uskoković, V., Ajduković, Z., Mihajilov Krstev, T.,& Uskoković, D.. (2015). Rapid bone regeneration with nano-hydroxyapatite coated with a chitosan-poly (D, L)-lactide-co-glycolide bone-filling material with osteocondactive and antimicrobial properties. in ITNANO2015: 3RD International Translational Nanomedicine Conference  21-26. June. 2015, Milocer, Hotel Maestral, Montenegro: Book of abstracts, 15-16.
https://hdl.handle.net/21.15107/rcub_dais_824

Ignjatović N, Uskoković V, Ajduković Z, Mihajilov Krstev T, Uskoković D. Rapid bone regeneration with nano-hydroxyapatite coated with a chitosan-poly (D, L)-lactide-co-glycolide bone-filling material with osteocondactive and antimicrobial properties. in ITNANO2015: 3RD International Translational Nanomedicine Conference  21-26. June. 2015, Milocer, Hotel Maestral, Montenegro: Book of abstracts. 2015;:15-16.
https://hdl.handle.net/21.15107/rcub_dais_824 .

Ignjatović, Nenad, Uskoković, Vuk, Ajduković, Zorica, Mihajilov Krstev, Tatjana, Uskoković, Dragan, "Rapid bone regeneration with nano-hydroxyapatite coated with a chitosan-poly (D, L)-lactide-co-glycolide bone-filling material with osteocondactive and antimicrobial properties" in ITNANO2015: 3RD International Translational Nanomedicine Conference  21-26. June. 2015, Milocer, Hotel Maestral, Montenegro: Book of abstracts (2015):15-16,
https://hdl.handle.net/21.15107/rcub_dais_824 .