title: An in vitro study of composites of poly(L-lactide-co-ε-caprolactone), β-tricalcium phosphate and ciprofloxacin intended for local treatment of osteomyelitis.
abstract: Osteomyelitis is a bacterial disease that can become chronic, and treatment often includes a surgical operation to remove infected bone. The aim of this study was to develop and investigate in vitro bone filling composite materials that release ciprofloxacin to kill any remaining bacteria and contain bioceramic to help the bone to heal. Three composites of poly(L-lactide-co-ε-caprolactone), β-tricalcium phosphate and ciprofloxacin were compounded using twin-screw extrusion and sterilized by gamma irradiation. Drug release and degradation of the composites were investigated in vitro for 52 weeks. The composite with 50 wt% of β-TCP had the most promising ciprofloxacin release profile. The ceramic component accelerated the drug release that occurred in three phases obeying first-order kinetics. Inhibition zone testing using bioluminescence showed that the released ciprofloxacin had effect in eradicating a common osteomyelitis causing bacteria Pseudomonas aeruginosa. During the in vitro degradation test series, molar weight of the polymer matrix of the composites decreased rapidly. Additionally, (1)H-NMR analysis showed that the polymer had blocky structure and the comonomer ratio changed during hydrolysis. The tested composites showed great potential to be developed into bone filler materials for the treatment of osteomyelitis or other bone related infections.
authors.affiliation: Department of Biomedical Engineering; Tampere University of Technology; Tampere, Finland; BioMediTech; Tampere, Finland.
authors.forename: Niina
authors.initials: N
authors.lastname: Ahola
authors.affiliation: Department of Biomedical Engineering; Tampere University of Technology; Tampere, Finland.
authors.forename: Noora
authors.initials: N
authors.lastname: Männistö
authors.affiliation: Department of Biomedical Engineering; Tampere University of Technology; Tampere, Finland; Bioretec Ltd.; Tampere, Finland.
authors.forename: Minna
authors.initials: M
authors.lastname: Veiranto
authors.affiliation: Department of Chemistry and Bioengineering Tampere; University of Technology; Tampere, Finland.
authors.forename: Matti
authors.initials: M
authors.lastname: Karp
authors.affiliation: Department of Biotechnology and Chemical Technology; School of Chemical Technology; Aalto University; Espoo, Finland.
authors.forename: Jaana
authors.initials: J
authors.lastname: Rich
authors.affiliation: Department of Chemistry and Bioengineering Tampere; University of Technology; Tampere, Finland.
authors.forename: Alexander
authors.initials: A
authors.lastname: Efimov
authors.affiliation: Department of Biotechnology and Chemical Technology; School of Chemical Technology; Aalto University; Espoo, Finland.
authors.forename: Jukka
authors.initials: J
authors.lastname: Seppälä
authors.affiliation: Department of Biomedical Engineering; Tampere University of Technology; Tampere, Finland; BioMediTech; Tampere, Finland.
authors.forename: Minna
authors.initials: M
authors.lastname: Kellomäki
mesh_terms: D000465:Algorithms; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000493:pharmacokinetics*; D001858:Bone Nails; D018786:Bone Substitutes / Q000737:chemistry / Q000493:pharmacokinetics*; D001842:Bone and Bones / Q000187:drug effects; D002130:Calcium Phosphates / Q000737:chemistry / Q000493:pharmacokinetics; D002516:Ceramics / Q000737:chemistry / Q000493:pharmacokinetics*; D002939:Ciprofloxacin / Q000737:chemistry / Q000493:pharmacokinetics*; D016503:Drug Delivery Systems; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D010019:Osteomyelitis / Q000188:drug therapy / Q000382:microbiology; D011091:Polyesters / Q000737:chemistry / Q000493:pharmacokinetics; D011550:Pseudomonas aeruginosa / Q000187:drug effects*; D013696:Temperature
chemical_list: D000900:Anti-Bacterial Agents; D018786:Bone Substitutes; D002130:Calcium Phosphates; D011091:Polyesters; C485817:beta-tricalcium phosphate; D002939:Ciprofloxacin; C062968:lactide-caprolactone copolymer
keywords: antibiotic; biodegradable; ciprofloxacin; composite; controlled drug delivery; poly(L-lactide-co-caprolactone)