Osteogenic and antimicrobial nanoparticulate calcium phosphate and poly-(d,l-lactide-co-glycolide) powders for the treatment of osteomyelitis

• Published in: Materials Science & Engineering C Vol. 33; no. 6; pp. 3362 - 3373
• Main Authors: Uskoković, Vuk, Hoover, Charles, Vukomanović, Marija, Uskoković, Dragan P., Desai, Tejal A.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.08.2013
• Subjects: Animals; Anti-Infective Agents - chemistry; Anti-Infective Agents - pharmacology; Anti-Infective Agents - therapeutic use; Antibiotics; Bacteria; Biocompatibility; Biomedical materials; Calcium phosphate; Calcium Phosphates - chemistry; Cell Line; Clindamycin - chemistry; Clindamycin - pharmacology; Clindamycin - therapeutic use; Collagen Type I - metabolism; Controlled drug delivery; Core Binding Factor Alpha 1 Subunit - metabolism; Hydrogen-Ion Concentration; Lactic Acid - chemistry; Mice; Nanocomposites; Nanomaterials; Nanoparticles - chemistry; Nanostructure; Osteoblasts - cytology; Osteoblasts - metabolism; Osteocalcin - metabolism; Osteogenesis; Osteogenesis - drug effects; Osteomyelitis; Osteomyelitis - drug therapy; Osteopontin - metabolism; Poly-lactide-co-glycolide; Polyglycolic Acid - chemistry; Polylactic Acid-Polyglycolic Acid Copolymer; Staphylococcus aureus; Staphylococcus aureus - drug effects; Osteomyelitis; Calcium phosphate; Controlled drug delivery; Poly-lactide-co-glycolide; Osteogenesis; Staphylococcus aureus
• ISSN: 0928-4931; 1873-0191
• DOI: 10.1016/j.msec.2013.04.023

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. [Display omitted] •Calcium phosphate particles w/t and w/o PLGA coating used as antibiotic carriers.•PLGA suppressed the burst release without diminishing the antibacterial efficacy.•Positive morphological response was induced in osteoblastic MC3T3-E1 cells.•Expression of 4 osteogenic markers was upregulated in the presence of particles.•Results suggest their ability to promote osteogenesis at the site of infection.