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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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