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Uskoković, Vuk

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  • Uskoković, Vuk (34)

Author's Bibliography

From molecules to nanoparticles to functional materials

Ignjatović, Nenad; Marković, Smilja; Jugović, Dragana; Uskoković, Vuk; Uskoković, Dragan

(Belgrade : Serbian Chemical Society, 2020)

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
ER  - 
@article{
author = "Ignjatović, Nenad and Marković, Smilja and Jugović, Dragana and Uskoković, Vuk and Uskoković, Dragan",
year = "2020",
url = "https://dais.sanu.ac.rs/123456789/10037",
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"
}

Calcium phosphate nanoparticles as intrinsic inorganic antimicrobials: In search of the key particle property

Uskoković, Vuk; Tang, Sean; Nikolić, Marko G.; Marković, Smilja; Wu, Victoria M.

(AIP Publishing LLC, 2019)

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  - http://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
ER  - 
@article{
author = "Uskoković, Vuk and Tang, Sean and Nikolić, Marko G. and Marković, Smilja and Wu, Victoria M.",
year = "2019",
url = "https://avs.scitation.org/doi/abs/10.1116/1.5090396, http://dais.sanu.ac.rs/123456789/6468",
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"
}
3
10
11
14

Calcium phosphate nanoparticles as intrinsic inorganic antimicrobials: In search of the key particle property

Uskoković, Vuk; Tang, Sean; Nikolić, Marko G.; Marković, Smilja; Wu, Victoria M.

(AIP Publishing LLC, 2019)

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  - http://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
ER  - 
@article{
author = "Uskoković, Vuk and Tang, Sean and Nikolić, Marko G. and Marković, Smilja and Wu, Victoria M.",
year = "2019",
url = "https://avs.scitation.org/doi/abs/10.1116/1.5090396, http://dais.sanu.ac.rs/123456789/6469",
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"
}
3
10
11
14

Rare-earth (Gd 3+ ,Yb 3+ /Tm 3+ , Eu 3+ ) co-doped hydroxyapatite as magnetic, up-conversion and down-conversion materials for multimodal imaging

Ignjatović, Nenad; Mančić, Lidija; Vuković, Marina; Stojanović, Zoran; Nikolić, Marko G.; Škapin, Srečo Davor; Jovanović, Sonja; Veselinović, Ljiljana; Uskoković, Vuk; Lazić, Snežana; Marković, Smilja; Lazarević, Miloš M.; Uskoković, Dragan

(Springer Nature, 2019)

TY  - JOUR
AU  - Ignjatović, Nenad
AU  - Mančić, Lidija
AU  - Vuković, Marina
AU  - Stojanović, Zoran
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  - http://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
ER  - 
@article{
author = "Ignjatović, Nenad and Mančić, Lidija and Vuković, Marina and Stojanović, Zoran 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",
url = "https://www.nature.com/articles/s41598-019-52885-0, http://dais.sanu.ac.rs/123456789/6950",
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"
}
1
14
9
14

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

Ignjatović, Nenad; Janković, Radmila; Uskoković, Vuk; Uskoković, Dragan

(2019)

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  - http://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
ER  - 
@article{
author = "Ignjatović, Nenad and Janković, Radmila and Uskoković, Vuk and Uskoković, Dragan",
year = "2019",
url = "https://pubs.rsc.org/en/content/articlelanding/2019/tx/c9tx00007k, http://dais.sanu.ac.rs/123456789/4961",
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"
}
2
3
2
3

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

Ignjatović, Nenad; Janković, Radmila; Uskoković, Vuk; Uskoković, Dragan

(2019)

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  - http://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
ER  - 
@article{
author = "Ignjatović, Nenad and Janković, Radmila and Uskoković, Vuk and Uskoković, Dragan",
year = "2019",
url = "https://pubs.rsc.org/en/content/articlelanding/2019/tx/c9tx00007k, http://dais.sanu.ac.rs/123456789/4847",
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"
}
2
3
2
3

Insights into the kinetics of thermally induced crystallization of amorphous calcium phosphate

Uskoković, Vuk; Marković, Smilja; Veselinović, Ljiljana; Škapin, Srečo Davor; Ignjatović, Nenad; Uskoković, Dragan

(Royal Society of Chemistry (RSC), 2018)

TY  - JOUR
AU  - Uskoković, Vuk
AU  - Marković, Smilja
AU  - Veselinović, Ljiljana
AU  - Škapin, Srečo Davor
AU  - Ignjatović, Nenad
AU  - Uskoković, Dragan
PY  - 2018
UR  - http://dais.sanu.ac.rs/123456789/4514
UR  - http://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
ER  - 
@article{
author = "Uskoković, Vuk and Marković, Smilja and Veselinović, Ljiljana and Škapin, Srečo Davor and Ignjatović, Nenad and Uskoković, Dragan",
year = "2018",
url = "http://dais.sanu.ac.rs/123456789/4514, http://dais.sanu.ac.rs/123456789/4554",
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"
}
17
16
20

Cell-selective toxicity of hydroxyapatite-chitosan oligosaccharide lactate particles loaded with a steroid cancer inhibitor

Ignjatović, Nenad; Sakač, Marija; Kuzminac, Ivana; Kojić, Vesna V.; Marković, Smilja; Wu, Victoria; Uskoković, Vuk; Uskoković, Dragan

(Belgrade : Materials Research Society of Serbia, 2018)

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  - http://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
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",
url = "http://dais.sanu.ac.rs/123456789/3662",
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"
}

Chitosan oligosaccharide lactate coated hydroxyapatite nanoparticles as a vehicle for the delivery of steroid drugs and the targeting of breast cancer cells

Ignjatović, Nenad; Sakač, Marija; Kuzminac, Ivana; Kojić, Vesna; Marković, Smilja; Vasiljević Radović, Dana; Wu, Victoria; Uskoković, Vuk; Uskoković, Dragan

(Royal Society of Chemistry, 2018)

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  - http://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
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",
url = "http://dais.sanu.ac.rs/123456789/4066",
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"
}
3
13
10
13

Chitosan oligosaccharide lactate coated hydroxyapatite nanoparticles as a vehicle for the delivery of steroid drugs and the targeting of breast cancer cells

Ignjatović, Nenad; Sakač, Marija; Kuzminac, Ivana; Kojić, Vesna; Marković, Smilja; Vasiljević Radović, Dana; Wu, Victoria M.; Uskoković, Vuk; Uskoković, Dragan

(Royal Society of Chemistry, 2018)

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  - http://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
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",
url = "https://pubs.rsc.org/en/content/articlelanding/2018/tb/c8tb01995a, http://dais.sanu.ac.rs/123456789/4509",
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"
}
3
13
10
13

Insights into the kinetics of thermally induced crystallization of amorphous calcium phosphate

Uskoković, Vuk; Marković, Smilja; Veselinović, Ljiljana; Škapin, Srečo Davor; Ignjatović, Nenad; Uskoković, Dragan

(Royal Society of Chemistry (RSC), 2018)

TY  - JOUR
AU  - Uskoković, Vuk
AU  - Marković, Smilja
AU  - Veselinović, Ljiljana
AU  - Škapin, Srečo Davor
AU  - Ignjatović, Nenad
AU  - Uskoković, Dragan
PY  - 2018
UR  - http://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
ER  - 
@article{
author = "Uskoković, Vuk and Marković, Smilja and Veselinović, Ljiljana and Škapin, Srečo Davor and Ignjatović, Nenad and Uskoković, Dragan",
year = "2018",
url = "http://dais.sanu.ac.rs/123456789/4514",
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"
}
17
16
20

Selective anticancer activity of hydroxyapatite/chitosan-poly(D,L)-lactide-co-glycolide particles loaded with an androstane-based cancer inhibitor

Ignjatović, Nenad; Penov Gaši, Katarina; Wu, Victoria; Ajduković, Jovana; Kojić, Vesna; Vasiljević Radović, Dana; Kuzmanović, Maja; Uskoković, Vuk; Uskoković, Dragan

(2016)

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  - http://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
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",
url = "http://dais.sanu.ac.rs/123456789/15984",
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"
}
15
15
19

Selective anticancer activity of hydroxyapatite/chitosan-poly(d,l)-lactide-co-glycolide particles loaded with an androstane-based cancer inhibitor

Ignjatović, Nenad; Penov Gaši, Katarina; Wu, Victoria; Ajduković, Jovana; Kojić, Vesna V.; Vasiljević Radović, Dana; Kuzmanović, Maja; Uskoković, Vuk; Uskoković, Dragan

(Elsevier, 2016)

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  - http://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
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",
url = "http://dais.sanu.ac.rs/123456789/15974",
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"
}
15
15
19

Hydrothermally processed 1D hydroxyapatite: Mechanism of formation and biocompatibility studies

Stojanović, Zoran S.; Ignjatović, Nenad; Wu, Victoria; Žunič, Vojka; Veselinović, Ljiljana; Škapin, Srečo Davor; Miljković, Miroslav; Uskoković, Vuk; Uskoković, Dragan

(2016)

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  - http://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
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",
url = "http://dais.sanu.ac.rs/123456789/15985",
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"
}
20
20
22

Hydrothermally processed 1D hydroxyapatite: Mechanism of formation and biocompatibility studies

Stojanović, Zoran S.; Ignjatović, Nenad; Wu, Victoria; Žunič, Vojka; Veselinović, Ljiljana; Škapin, Srečo Davor; Miljković, Miroslav; Uskoković, Vuk; Uskoković, Dragan

(Elsevier, 2016)

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  - http://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
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",
url = "http://dais.sanu.ac.rs/123456789/16006",
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"
}
20
20
22

Chitosan-PLGA polymer blends as coatings for hydroxyapatite nanoparticles and their effect on antimicrobial properties, osteoconductivity and regeneration of osseous tissues

Ignjatović, Nenad; Wu, Victoria; Ajduković, Zorica; Mihajilov Krstev, Tatjana; Uskoković, Vuk; Uskoković, Dragan

(2016)

TY  - JOUR
AU  - Ignjatović, Nenad
AU  - Wu, Victoria
AU  - Ajduković, Zorica
AU  - Mihajilov Krstev, Tatjana
AU  - Uskoković, Vuk
AU  - Uskoković, Dragan
PY  - 2016
UR  - http://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
ER  - 
@article{
author = "Ignjatović, Nenad and Wu, Victoria and Ajduković, Zorica and Mihajilov Krstev, Tatjana and Uskoković, Vuk and Uskoković, Dragan",
year = "2016",
url = "http://dais.sanu.ac.rs/123456789/15983",
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"
}
49
47
48

Tumor-selective hybrid system based on hydroxyapatite nanocarrier, chitosan, poly(lactic-co-glycolic acid) and androstan derivate

Ignjatović, Nenad; Penov Gaši, Katarina; Wu, Victoria; Ajduković, Jovana; Kojić, Vesna; Vasiljević Radović, Dana; Uskoković, Vuk; Uskoković, Dragan

(Belgrade : Materials Research Society of Serbia, 2016)

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  - http://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
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",
url = "http://dais.sanu.ac.rs/123456789/896",
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"
}

Chitosan-PLGA polymer blends as coatings for hydroxyapatite nanoparticles and their effect on antimicrobial properties, osteoconductivity and regeneration of osseous tissues

Ignjatović, Nenad; Wu, Victoria; Ajduković, Zorica; Mihajilov Krstev, Tatjana; Uskoković, Vuk; Uskoković, Dragan

(Elsevier, 2016)

TY  - JOUR
AU  - Ignjatović, Nenad
AU  - Wu, Victoria
AU  - Ajduković, Zorica
AU  - Mihajilov Krstev, Tatjana
AU  - Uskoković, Vuk
AU  - Uskoković, Dragan
PY  - 2016
UR  - http://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
ER  - 
@article{
author = "Ignjatović, Nenad and Wu, Victoria and Ajduković, Zorica and Mihajilov Krstev, Tatjana and Uskoković, Vuk and Uskoković, Dragan",
year = "2016",
url = "http://dais.sanu.ac.rs/123456789/15975",
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"
}
49
47
48

Rapid bone regeneration with nano-hydroxyapatite coated with a chitosan-poly (D, L)-lactide-co-glycolide bone-filling material with osteocondactive and antimicrobial properties

Ignjatović, Nenad; Uskoković, Vuk; Ajduković, Zorica; Mihajilov Krstev, Tatjana; Uskoković, Dragan

(2015)

TY  - CONF
AU  - Ignjatović, Nenad
AU  - Uskoković, Vuk
AU  - Ajduković, Zorica
AU  - Mihajilov Krstev, Tatjana
AU  - Uskoković, Dragan
PY  - 2015
UR  - http://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
ER  - 
@conference{
author = "Ignjatović, Nenad and Uskoković, Vuk and Ajduković, Zorica and Mihajilov Krstev, Tatjana and Uskoković, Dragan",
year = "2015",
url = "http://dais.sanu.ac.rs/123456789/824",
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"
}

Composite PLGA/AgNpPGA/AscH Nanospheres with Combined Osteoinductive, Antioxidative, and Antimicrobial Activities

Stevanović, Magdalena; Uskoković, Vuk; Filipović, Miloš; Škapin, Srečo Davor; Uskoković, Dragan

(2013)

TY  - JOUR
AU  - Stevanović, Magdalena
AU  - Uskoković, Vuk
AU  - Filipović, Miloš
AU  - Škapin, Srečo Davor
AU  - Uskoković, Dragan
PY  - 2013
UR  - http://dais.sanu.ac.rs/123456789/15986
AB  - The global rise in the resistance of pathogens to conventional antibiotics has created an intensive search for alternative materials with antimicrobial properties. This study is performed with an intention to investigate the combined effects of poly(L-glutamic acid)-capped silver nanoparticles (AgNpPGA) and ascorbic acid (AscH) encapsulated within freeze-dried poly(lactide-co-glycolide) (PLGA) nanospheres to obtain a nanomaterial with simultaneous osteoinductive, antioxidative, and prolonged antimicrobial properties. The influence of PLGA/AgNpPGA/AscH particles on (i) viability and super-oxide production of human umbilical vein endothelial cells in vitro, (ii) morphology and expression of osteogenic markers in osteoblastic MC3T3-E1 cells in vitro, and (iii) antimicrobial activity against a Gram-positive bacterium, methicillin-resistant Staphylococcus aureus, and a Gram-negative bacterium, Escherichia coli, was investigated. PLGA/AgNpPGA/AscH nanoparticles showed a superior and extended antibacterial activity against both types of bacteria. The nanoparticles appeared to be capable of delivering ascorbate to the cells, which was evidenced by the significant decrease in the level of superoxides in human umbilical vein endothelial cells and which could have a therapeutic potential in preventing oxidative stress. PLGA/AgNpPGA/AscH nanoparticles had a positive effect on MC3T3-E1 osteoblastic cells in vitro, promoting: (i) an intimate contact with the cells and preservation of their healthy morphologies; (ii) unreduced cell viability; and (iii) multiple-fold upregulation of two osteogenic markers: osteocalcin and type I procollagen. It is concluded that PLGA/AgNpPGA/AscH nanospheres present a promising new material for the treatment of infections and use in wound dressings and other prophylactic applications.
T2  - ACS Applied Materials and Interfaces
T1  - Composite PLGA/AgNpPGA/AscH Nanospheres with Combined Osteoinductive, Antioxidative, and Antimicrobial Activities
SP  - 9034
EP  - 9042
VL  - 5
IS  - 18
DO  - 10.1021/am402237g
ER  - 
@article{
author = "Stevanović, Magdalena and Uskoković, Vuk and Filipović, Miloš and Škapin, Srečo Davor and Uskoković, Dragan",
year = "2013",
url = "http://dais.sanu.ac.rs/123456789/15986",
abstract = "The global rise in the resistance of pathogens to conventional antibiotics has created an intensive search for alternative materials with antimicrobial properties. This study is performed with an intention to investigate the combined effects of poly(L-glutamic acid)-capped silver nanoparticles (AgNpPGA) and ascorbic acid (AscH) encapsulated within freeze-dried poly(lactide-co-glycolide) (PLGA) nanospheres to obtain a nanomaterial with simultaneous osteoinductive, antioxidative, and prolonged antimicrobial properties. The influence of PLGA/AgNpPGA/AscH particles on (i) viability and super-oxide production of human umbilical vein endothelial cells in vitro, (ii) morphology and expression of osteogenic markers in osteoblastic MC3T3-E1 cells in vitro, and (iii) antimicrobial activity against a Gram-positive bacterium, methicillin-resistant Staphylococcus aureus, and a Gram-negative bacterium, Escherichia coli, was investigated. PLGA/AgNpPGA/AscH nanoparticles showed a superior and extended antibacterial activity against both types of bacteria. The nanoparticles appeared to be capable of delivering ascorbate to the cells, which was evidenced by the significant decrease in the level of superoxides in human umbilical vein endothelial cells and which could have a therapeutic potential in preventing oxidative stress. PLGA/AgNpPGA/AscH nanoparticles had a positive effect on MC3T3-E1 osteoblastic cells in vitro, promoting: (i) an intimate contact with the cells and preservation of their healthy morphologies; (ii) unreduced cell viability; and (iii) multiple-fold upregulation of two osteogenic markers: osteocalcin and type I procollagen. It is concluded that PLGA/AgNpPGA/AscH nanospheres present a promising new material for the treatment of infections and use in wound dressings and other prophylactic applications.",
journal = "ACS Applied Materials and Interfaces",
title = "Composite PLGA/AgNpPGA/AscH Nanospheres with Combined Osteoinductive, Antioxidative, and Antimicrobial Activities",
pages = "9034-9042",
volume = "5",
number = "18",
doi = "10.1021/am402237g"
}
31
31
30

Composite PLGA/AgNpPGA/AscH nanospheres with combined osteoinductive, antioxidative and antimicrobial activities

Stevanović, Magdalena; Uskoković, Vuk; Filipović, Miloš; Škapin, Srečo Davor; Uskoković, Dragan

(American Chemical Society, 2013)

TY  - JOUR
AU  - Stevanović, Magdalena
AU  - Uskoković, Vuk
AU  - Filipović, Miloš
AU  - Škapin, Srečo Davor
AU  - Uskoković, Dragan
PY  - 2013
UR  - http://dais.sanu.ac.rs/123456789/381
AB  - The global rise in the resistance of pathogens to conventional antibiotics has created an intensive search for alternative materials with antimicrobial properties. This study is performed with an intention to investigate the combined effects of poly(l-glutamic acid)-capped silver nanoparticles (AgNpPGA) and ascorbic acid (AscH) encapsulated within freeze-dried poly(lactide-co-glycolide) (PLGA) nanospheres to obtain a nanomaterial with simultaneous osteoinductive, antioxidative, and prolonged antimicrobial properties. The influence of PLGA/AgNpPGA/AscH particles on (i) viability and superoxide production of human umbilical vein endothelial cells in vitro, (ii) morphology and expression of osteogenic markers in osteoblastic MC3T3-E1 cells in vitro, and (iii) antimicrobial activity against a Gram-positive bacterium, methicillin-resistant Staphylococcus aureus, and a Gram-negative bacterium, Escherichia coli, was investigated. PLGA/AgNpPGA/AscH nanoparticles showed a superior and extended antibacterial activity against both types of bacteria. The nanoparticles appeared to be capable of delivering ascorbate to the cells, which was evidenced by the significant decrease in the level of superoxides in human umbilical vein endothelial cells and which could have a therapeutic potential in preventing oxidative stress. PLGA/AgNpPGA/AscH nanoparticles had a positive effect on MC3T3-E1 osteoblastic cells in vitro, promoting: (i) an intimate contact with the cells and preservation of their healthy morphologies; (ii) unreduced cell viability; and (iii) multiple-fold upregulation of two osteogenic markers: osteocalcin and type I procollagen. It is concluded that PLGA/AgNpPGA/AscH nanospheres present a promising new material for the treatment of infections and use in wound dressings and other prophylactic applications.
PB  - American Chemical Society
T2  - ACS Applied Materials and Interfaces
T1  - Composite PLGA/AgNpPGA/AscH nanospheres with combined osteoinductive, antioxidative and antimicrobial activities
SP  - 9034
EP  - 9042
VL  - 5
IS  - 18
DO  - 10.1021/am402237g
ER  - 
@article{
author = "Stevanović, Magdalena and Uskoković, Vuk and Filipović, Miloš and Škapin, Srečo Davor and Uskoković, Dragan",
year = "2013",
url = "http://dais.sanu.ac.rs/123456789/381",
abstract = "The global rise in the resistance of pathogens to conventional antibiotics has created an intensive search for alternative materials with antimicrobial properties. This study is performed with an intention to investigate the combined effects of poly(l-glutamic acid)-capped silver nanoparticles (AgNpPGA) and ascorbic acid (AscH) encapsulated within freeze-dried poly(lactide-co-glycolide) (PLGA) nanospheres to obtain a nanomaterial with simultaneous osteoinductive, antioxidative, and prolonged antimicrobial properties. The influence of PLGA/AgNpPGA/AscH particles on (i) viability and superoxide production of human umbilical vein endothelial cells in vitro, (ii) morphology and expression of osteogenic markers in osteoblastic MC3T3-E1 cells in vitro, and (iii) antimicrobial activity against a Gram-positive bacterium, methicillin-resistant Staphylococcus aureus, and a Gram-negative bacterium, Escherichia coli, was investigated. PLGA/AgNpPGA/AscH nanoparticles showed a superior and extended antibacterial activity against both types of bacteria. The nanoparticles appeared to be capable of delivering ascorbate to the cells, which was evidenced by the significant decrease in the level of superoxides in human umbilical vein endothelial cells and which could have a therapeutic potential in preventing oxidative stress. PLGA/AgNpPGA/AscH nanoparticles had a positive effect on MC3T3-E1 osteoblastic cells in vitro, promoting: (i) an intimate contact with the cells and preservation of their healthy morphologies; (ii) unreduced cell viability; and (iii) multiple-fold upregulation of two osteogenic markers: osteocalcin and type I procollagen. It is concluded that PLGA/AgNpPGA/AscH nanospheres present a promising new material for the treatment of infections and use in wound dressings and other prophylactic applications.",
publisher = "American Chemical Society",
journal = "ACS Applied Materials and Interfaces",
title = "Composite PLGA/AgNpPGA/AscH nanospheres with combined osteoinductive, antioxidative and antimicrobial activities",
pages = "9034-9042",
volume = "5",
number = "18",
doi = "10.1021/am402237g"
}
31
31
30

Multifunctional hydroxyapatite and poly(D,L-lactide-co-glycolide) nanoparticles for the local delivery of cholecalciferol

Ignjatović, Nenad; Uskoković, Vuk; Ajduković, Zorica; Uskoković, Dragan

(Elsevier, 2013)

TY  - JOUR
AU  - Ignjatović, Nenad
AU  - Uskoković, Vuk
AU  - Ajduković, Zorica
AU  - Uskoković, Dragan
PY  - 2013
UR  - http://dais.sanu.ac.rs/123456789/354
AB  - Cholecalciferol, vitamin D3, plays an important role in bone metabolism by regulating extracellular levels of calcium. Presented here is a study on the effects of the local delivery of cholecalciferol (D3) using nanoparticulate carriers composed of hydroxyapatite (HAp) and poly(d,l-lactide-co-glycolide) (PLGA). Multifunctional nanoparticulate HAp-based powders were prepared for the purpose of: (a) either fast or sustained, local delivery of cholecalciferol, and (b) the secondary, osteoconductive and defect-filling effect of the carrier itself. Two types of HAp-based powders with particles of narrowly dispersed sizes in the nano range were prepared and tested in this study: HAp nanoparticles as direct cholecalciferol delivery agents and HAp nanoparticles coated with cholecalciferol-loaded poly(d,l)-lactide-co-glycolide (HAp/D3/PLGA).

Satisfying biocompatibility of particulate systems, when incubated in contact with MC3T3-E1 osteoblastic cells in vitro, was observed for HAp/D3/PLGA and pure HAp. In contrast, an extensively fast release of cholecalciferol from the system comprising HAp nanoparticles coated with cholecalciferol (HAp/D3) triggered necrosis of the osteoblastic cells in vitro. Artificial defects induced in the osteoporotic bone of the rat mandible were successfully reconstructed following implantation of cholecalciferol-coated HAp nanoparticles as well as those comprising HAp nanoparticles coated with cholecalciferol-loaded PLGA (HAp/D3/PLGA). The greatest levels of enhanced angiogenesis, vascularization, osteogenesis and bone structure differentiation were achieved upon the implementation of HAp/D3/PLGA systems.
PB  - Elsevier
T2  - Materials Science and Engineering: C
T1  - Multifunctional hydroxyapatite and poly(D,L-lactide-co-glycolide) nanoparticles for the local delivery of cholecalciferol
SP  - 943
EP  - 950
VL  - 33
IS  - 2
DO  - 10.1016/j.msec.2012.11.026
ER  - 
@article{
author = "Ignjatović, Nenad and Uskoković, Vuk and Ajduković, Zorica and Uskoković, Dragan",
year = "2013",
url = "http://dais.sanu.ac.rs/123456789/354",
abstract = "Cholecalciferol, vitamin D3, plays an important role in bone metabolism by regulating extracellular levels of calcium. Presented here is a study on the effects of the local delivery of cholecalciferol (D3) using nanoparticulate carriers composed of hydroxyapatite (HAp) and poly(d,l-lactide-co-glycolide) (PLGA). Multifunctional nanoparticulate HAp-based powders were prepared for the purpose of: (a) either fast or sustained, local delivery of cholecalciferol, and (b) the secondary, osteoconductive and defect-filling effect of the carrier itself. Two types of HAp-based powders with particles of narrowly dispersed sizes in the nano range were prepared and tested in this study: HAp nanoparticles as direct cholecalciferol delivery agents and HAp nanoparticles coated with cholecalciferol-loaded poly(d,l)-lactide-co-glycolide (HAp/D3/PLGA).

Satisfying biocompatibility of particulate systems, when incubated in contact with MC3T3-E1 osteoblastic cells in vitro, was observed for HAp/D3/PLGA and pure HAp. In contrast, an extensively fast release of cholecalciferol from the system comprising HAp nanoparticles coated with cholecalciferol (HAp/D3) triggered necrosis of the osteoblastic cells in vitro. Artificial defects induced in the osteoporotic bone of the rat mandible were successfully reconstructed following implantation of cholecalciferol-coated HAp nanoparticles as well as those comprising HAp nanoparticles coated with cholecalciferol-loaded PLGA (HAp/D3/PLGA). The greatest levels of enhanced angiogenesis, vascularization, osteogenesis and bone structure differentiation were achieved upon the implementation of HAp/D3/PLGA systems.",
publisher = "Elsevier",
journal = "Materials Science and Engineering: C",
title = "Multifunctional hydroxyapatite and poly(D,L-lactide-co-glycolide) nanoparticles for the local delivery of cholecalciferol",
pages = "943-950",
volume = "33",
number = "2",
doi = "10.1016/j.msec.2012.11.026"
}
39
34
41

Osteogenic and Antimicrobial Nanoparticulate Calcium Phosphate and Poly-(D, L-Lactide-co-Glycolide) Powders for the Treatment of Osteomyelitis

Uskoković, Vuk; Hoover, Charles; Vukomanović, Marija; Uskoković, Dragan; Desai, Tejal A.

(2013)

TY  - JOUR
AU  - Uskoković, Vuk
AU  - Hoover, Charles
AU  - Vukomanović, Marija
AU  - Uskoković, Dragan
AU  - Desai, Tejal A.
PY  - 2013
UR  - http://dais.sanu.ac.rs/123456789/15989
AB  - Development of a material for simultaneous sustained and localized delivery of antibiotics and induction of spontaneous regeneration of hard tissues affected by osteomyelitis stands for an important clinical need. In this work, a comparative analysis of the bacterial and osteoblastic cell response to two different nanoparticulate carriers of clindamycin, an antibiotic commonly prescribed in the treatment of bone infection, one composed of calcium phosphate and the other comprising poly-(D,L-lactide-co-glycolide)-coated calcium phosphate, was carried out. Three different non-cytotoxic phases of calcium phosphate, exhibiting dissolution and drug release profiles in the range of one week to two months to one year, respectively, were included in the analysis: monetite, amorphous calcium phosphate and hydroxyapatite. Spherical morphologies and narrow size distribution of both types of nanopowders were confirmed in transmission and scanning electron microscopic analyses. The antibiotic-containing powders exhibited sustained drug release contingent upon the degradation rate of the carrier. Assessment of the antibacterial performance of the antibiotic-encapsulated powders against Staphylococcus aureus, the most common pathogen isolated from infected bone, yielded satisfactory results both in broths and on blood agar plates for all the analyzed powders. In contrast, no cytotoxic behavior was detected upon the incubation of the antibiotic powders with the osteoblastic MC3T3-E1 cell line for up to three weeks. The cells were shown to engage in a close contact with the antibiotic-containing particles, irrespective of their internal or surface phase composition, polymeric or mineral. At the same time, both types of particles upregulated the expression of osteogenic markers osteocalcin, osteopontin, Runx2 and protocollagen type I, suggesting their ability to promote osteogenesis and enhance remineralization of the infected site in addition to eliminating the bacterial source of infection.
T2  - Materials Science and Engineering: C
T1  - Osteogenic and Antimicrobial Nanoparticulate Calcium Phosphate and Poly-(D, L-Lactide-co-Glycolide) Powders for the Treatment of Osteomyelitis
SP  - 3362
EP  - 3373
VL  - 33
IS  - 6
DO  - 10.1016/j.msec.2013.04.023
ER  - 
@article{
author = "Uskoković, Vuk and Hoover, Charles and Vukomanović, Marija and Uskoković, Dragan and Desai, Tejal A.",
year = "2013",
url = "http://dais.sanu.ac.rs/123456789/15989",
abstract = "Development of a material for simultaneous sustained and localized delivery of antibiotics and induction of spontaneous regeneration of hard tissues affected by osteomyelitis stands for an important clinical need. In this work, a comparative analysis of the bacterial and osteoblastic cell response to two different nanoparticulate carriers of clindamycin, an antibiotic commonly prescribed in the treatment of bone infection, one composed of calcium phosphate and the other comprising poly-(D,L-lactide-co-glycolide)-coated calcium phosphate, was carried out. Three different non-cytotoxic phases of calcium phosphate, exhibiting dissolution and drug release profiles in the range of one week to two months to one year, respectively, were included in the analysis: monetite, amorphous calcium phosphate and hydroxyapatite. Spherical morphologies and narrow size distribution of both types of nanopowders were confirmed in transmission and scanning electron microscopic analyses. The antibiotic-containing powders exhibited sustained drug release contingent upon the degradation rate of the carrier. Assessment of the antibacterial performance of the antibiotic-encapsulated powders against Staphylococcus aureus, the most common pathogen isolated from infected bone, yielded satisfactory results both in broths and on blood agar plates for all the analyzed powders. In contrast, no cytotoxic behavior was detected upon the incubation of the antibiotic powders with the osteoblastic MC3T3-E1 cell line for up to three weeks. The cells were shown to engage in a close contact with the antibiotic-containing particles, irrespective of their internal or surface phase composition, polymeric or mineral. At the same time, both types of particles upregulated the expression of osteogenic markers osteocalcin, osteopontin, Runx2 and protocollagen type I, suggesting their ability to promote osteogenesis and enhance remineralization of the infected site in addition to eliminating the bacterial source of infection.",
journal = "Materials Science and Engineering: C",
title = "Osteogenic and Antimicrobial Nanoparticulate Calcium Phosphate and Poly-(D, L-Lactide-co-Glycolide) Powders for the Treatment of Osteomyelitis",
pages = "3362-3373",
volume = "33",
number = "6",
doi = "10.1016/j.msec.2013.04.023"
}
36
38
39

Multifunctional hydroxyapatite and poly(D,L-lactide-co-glycolide) nanoparticles for the local delivery of cholecalciferol

Ignjatović, Nenad; Uskoković, Vuk; Ajduković, Zorica; Uskoković, Dragan

(2013)

TY  - JOUR
AU  - Ignjatović, Nenad
AU  - Uskoković, Vuk
AU  - Ajduković, Zorica
AU  - Uskoković, Dragan
PY  - 2013
UR  - http://dais.sanu.ac.rs/123456789/15982
AB  - Cholecalciferol, vitamin D3, plays an important role in bone metabolism by regulating extracellular levels of calcium. Presented here is a study on the effects of the local delivery of cholecalciferol (D3) using nanoparticulate carriers composed of hydroxyapatite (HAp) and poly(D,L-lactide-co-glycolide) (PLGA). Multifunctional nanoparticulate HAp-based powders were prepared for the purpose of: (a) either fast or sustained, local delivery of cholecalciferol, and (b) the secondary, osteoconductive and defect-filling effect of the carrier itself. Two types of HAp-based powders with particles of narrowly dispersed sizes in the nano range were prepared and tested in this study: HAp nanoparticles as direct cholecalciferol delivery agents and HAp nanoparticles coated with cholecalciferol-loaded poly(D,L)-lactide-co-glycolide (HAp/D3/PLGA).

Satisfying biocompatibility of particulate systems, when incubated in contact with MC3T3-E1 osteoblastic cells in vitro, was observed for HAp/D3/PLGA and pure HAp. In contrast, an extensively fast release of cholecalciferol from the system comprising HAp nanoparticles coated with cholecalciferol (HAp/D3) triggered necrosis of the osteoblastic cells in vitro. Artificial defects induced in the osteoporotic bone of the rat mandible were successfully reconstructed following implantation of cholecalciferol-coated HAp nanoparticles as well as those comprising HAp nanoparticles coated with cholecalciferol-loaded PLGA (HAp/D3/PLGA). The greatest levels of enhanced angiogenesis, vascularization, osteogenesis and bone structure differentiation were achieved upon the implementation of HAp/D3/PLGA systems.
T2  - Materials Science and Engineering: C
T1  - Multifunctional hydroxyapatite and poly(D,L-lactide-co-glycolide) nanoparticles for the local delivery of cholecalciferol
SP  - 943
EP  - 950
VL  - 33
IS  - 2
DO  - 10.1016/j.msec.2012.11.026
ER  - 
@article{
author = "Ignjatović, Nenad and Uskoković, Vuk and Ajduković, Zorica and Uskoković, Dragan",
year = "2013",
url = "http://dais.sanu.ac.rs/123456789/15982",
abstract = "Cholecalciferol, vitamin D3, plays an important role in bone metabolism by regulating extracellular levels of calcium. Presented here is a study on the effects of the local delivery of cholecalciferol (D3) using nanoparticulate carriers composed of hydroxyapatite (HAp) and poly(D,L-lactide-co-glycolide) (PLGA). Multifunctional nanoparticulate HAp-based powders were prepared for the purpose of: (a) either fast or sustained, local delivery of cholecalciferol, and (b) the secondary, osteoconductive and defect-filling effect of the carrier itself. Two types of HAp-based powders with particles of narrowly dispersed sizes in the nano range were prepared and tested in this study: HAp nanoparticles as direct cholecalciferol delivery agents and HAp nanoparticles coated with cholecalciferol-loaded poly(D,L)-lactide-co-glycolide (HAp/D3/PLGA).

Satisfying biocompatibility of particulate systems, when incubated in contact with MC3T3-E1 osteoblastic cells in vitro, was observed for HAp/D3/PLGA and pure HAp. In contrast, an extensively fast release of cholecalciferol from the system comprising HAp nanoparticles coated with cholecalciferol (HAp/D3) triggered necrosis of the osteoblastic cells in vitro. Artificial defects induced in the osteoporotic bone of the rat mandible were successfully reconstructed following implantation of cholecalciferol-coated HAp nanoparticles as well as those comprising HAp nanoparticles coated with cholecalciferol-loaded PLGA (HAp/D3/PLGA). The greatest levels of enhanced angiogenesis, vascularization, osteogenesis and bone structure differentiation were achieved upon the implementation of HAp/D3/PLGA systems.",
journal = "Materials Science and Engineering: C",
title = "Multifunctional hydroxyapatite and poly(D,L-lactide-co-glycolide) nanoparticles for the local delivery of cholecalciferol",
pages = "943-950",
volume = "33",
number = "2",
doi = "10.1016/j.msec.2012.11.026"
}
39
34
41

Nanoparticles of cobalt-substituted hydroxyapatite in regeneration of mandibular osteoporotic bones

Ignjatović, Nenad; Ajduković, Zorica; Savić, Vojin; Najman, Stevo; Mihailović, Dragan; Vasiljević, Perica; Stojanović, Zoran S.; Uskoković, Vuk; Uskoković, Dragan

(2013)

TY  - JOUR
AU  - Ignjatović, Nenad
AU  - Ajduković, Zorica
AU  - Savić, Vojin
AU  - Najman, Stevo
AU  - Mihailović, Dragan
AU  - Vasiljević, Perica
AU  - Stojanović, Zoran S.
AU  - Uskoković, Vuk
AU  - Uskoković, Dragan
PY  - 2013
UR  - http://dais.sanu.ac.rs/123456789/572
AB  - Indications exist that paramagnetic calcium phosphates may be able to promote regeneration of bone faster than their regular, diamagnetic counterparts. In this study, analyzed was the influence of paramagnetic cobalt-substituted hydroxyapatite nanoparticles on osteoporotic alveolar bone regeneration in rats. Simultaneously, biocompatibility of the material was tested in vitro, on osteoblastic MC3T3-E1 and epithelial Caco-2 cells in culture. The material was shown to be biocompatible and nontoxic when added to epithelial monolayers in vitro, while it caused a substantial decrease in the cell viability as well as deformation of the cytoskeleton and cell morphology when incubated with the osteoblastic cells. In the course of 6 months after the implantation of the material containing different amounts of cobalt, ranging from 5 to 12 wt%, in the osteoporotic alveolar bone of the lower jaw, the following parameters were investigated: histopathological parameters, alkaline phosphatase and alveolar bone density. The best result in terms of osteoporotic bone tissue regeneration was observed for hydroxyapatite nanoparticles with the largest content of cobalt ions. The histological analysis showed a high level of reparatory ability of the nanoparticulate material implanted in the bone defect, paralleled by a corresponding increase in the alveolar bone density. The combined effect of growth factors from autologous plasma admixed to cobalt-substituted hydroxyapatite was furthermore shown to have a crucial effect on the augmented osteoporotic bone regeneration upon the implantation of the biomaterial investigated in this study.
T2  - Journal of Materials Science: Materials in Medicine
T1  - Nanoparticles of cobalt-substituted hydroxyapatite in regeneration of mandibular osteoporotic bones
SP  - 343
EP  - 354
VL  - 24
IS  - 2
DO  - 10.1007/s10856-012-4793-1
ER  - 
@article{
author = "Ignjatović, Nenad and Ajduković, Zorica and Savić, Vojin and Najman, Stevo and Mihailović, Dragan and Vasiljević, Perica and Stojanović, Zoran S. and Uskoković, Vuk and Uskoković, Dragan",
year = "2013",
url = "http://dais.sanu.ac.rs/123456789/572",
abstract = "Indications exist that paramagnetic calcium phosphates may be able to promote regeneration of bone faster than their regular, diamagnetic counterparts. In this study, analyzed was the influence of paramagnetic cobalt-substituted hydroxyapatite nanoparticles on osteoporotic alveolar bone regeneration in rats. Simultaneously, biocompatibility of the material was tested in vitro, on osteoblastic MC3T3-E1 and epithelial Caco-2 cells in culture. The material was shown to be biocompatible and nontoxic when added to epithelial monolayers in vitro, while it caused a substantial decrease in the cell viability as well as deformation of the cytoskeleton and cell morphology when incubated with the osteoblastic cells. In the course of 6 months after the implantation of the material containing different amounts of cobalt, ranging from 5 to 12 wt%, in the osteoporotic alveolar bone of the lower jaw, the following parameters were investigated: histopathological parameters, alkaline phosphatase and alveolar bone density. The best result in terms of osteoporotic bone tissue regeneration was observed for hydroxyapatite nanoparticles with the largest content of cobalt ions. The histological analysis showed a high level of reparatory ability of the nanoparticulate material implanted in the bone defect, paralleled by a corresponding increase in the alveolar bone density. The combined effect of growth factors from autologous plasma admixed to cobalt-substituted hydroxyapatite was furthermore shown to have a crucial effect on the augmented osteoporotic bone regeneration upon the implantation of the biomaterial investigated in this study.",
journal = "Journal of Materials Science: Materials in Medicine",
title = "Nanoparticles of cobalt-substituted hydroxyapatite in regeneration of mandibular osteoporotic bones",
pages = "343-354",
volume = "24",
number = "2",
doi = "10.1007/s10856-012-4793-1"
}
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