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

Authorized Users Only
2013
Authors
Uskoković, Vuk
Hoover, Charles
Vukomanović, Marija
Uskoković, Dragan
Desai, Tejal A.
Article (Published version)
Metadata
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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-conta...ining 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.

Keywords:
calcium phosphate / controlled drug delivery / osteogenesis / osteomyelitis / poly-lactide-co-glycolide
Source:
Materials Science and Engineering: C, 2013, 33, 6, 3362-3373
Publisher:
  • Elsevier
Funding / projects:
  • United States National Institutes of Health (NIH) / National Institute of Dental and Craniofacial Research (NIDCR), Grant K99-DE021416
Note:
  • Peer-reviewed manuscript: https://hdl.handle.net/21.15107/rcub_dais_15989

DOI: 10.1016/j.msec.2013.04.023

ISSN: 0928-4931

PubMed: 23706222

WoS: 000320973000034

Scopus: 2-s2.0-84878259144
[ Google Scholar ]
46
39
Handle
https://hdl.handle.net/21.15107/rcub_dais_382
URI
https://dais.sanu.ac.rs/123456789/382
Collections
  • ИТН САНУ - Општа колекција / ITS SASA - General collection
Institution/Community
Институт техничких наука САНУ / Institute of Technical Sciences of SASA
TY  - JOUR
AU  - Uskoković, Vuk
AU  - Hoover, Charles
AU  - Vukomanović, Marija
AU  - Uskoković, Dragan
AU  - Desai, Tejal A.
PY  - 2013
UR  - https://dais.sanu.ac.rs/123456789/382
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.
PB  - Elsevier
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
UR  - https://hdl.handle.net/21.15107/rcub_dais_382
ER  - 
@article{
author = "Uskoković, Vuk and Hoover, Charles and Vukomanović, Marija and Uskoković, Dragan and Desai, Tejal A.",
year = "2013",
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.",
publisher = "Elsevier",
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",
url = "https://hdl.handle.net/21.15107/rcub_dais_382"
}
Uskoković, V., Hoover, C., Vukomanović, M., Uskoković, D.,& Desai, T. A.. (2013). Osteogenic and Antimicrobial Nanoparticulate Calcium Phosphate and Poly-(D, L-Lactide-co-Glycolide) Powders for the Treatment of Osteomyelitis. in Materials Science and Engineering: C
Elsevier., 33(6), 3362-3373.
https://doi.org/10.1016/j.msec.2013.04.023
https://hdl.handle.net/21.15107/rcub_dais_382
Uskoković V, Hoover C, Vukomanović M, Uskoković D, Desai TA. Osteogenic and Antimicrobial Nanoparticulate Calcium Phosphate and Poly-(D, L-Lactide-co-Glycolide) Powders for the Treatment of Osteomyelitis. in Materials Science and Engineering: C. 2013;33(6):3362-3373.
doi:10.1016/j.msec.2013.04.023
https://hdl.handle.net/21.15107/rcub_dais_382 .
Uskoković, Vuk, Hoover, Charles, Vukomanović, Marija, Uskoković, Dragan, Desai, Tejal A., "Osteogenic and Antimicrobial Nanoparticulate Calcium Phosphate and Poly-(D, L-Lactide-co-Glycolide) Powders for the Treatment of Osteomyelitis" in Materials Science and Engineering: C, 33, no. 6 (2013):3362-3373,
https://doi.org/10.1016/j.msec.2013.04.023 .,
https://hdl.handle.net/21.15107/rcub_dais_382 .

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