title: Electrospun polyurethane nanofiber scaffolds with ciprofloxacin oligomer versus free ciprofloxacin: Effect on drug release and cell attachment.
abstract: An electrospun degradable polycarbonate urethane (PCNU) nanofiber scaffold loaded with antibiotic was investigated in terms of antibacterial efficacy and cell compatibility for potential use in gingival tissue engineering. Antimicrobial oligomer (AO), a compound which consists of two molecules of ciprofloxacin (CF) covalently bound via hydrolysable linkages to triethylene glycol (TEG), was incorporated via a one-step blend electrospinning process using a single solvent system at 7 and 15% w/w equivalent CF with respect to the PCNU. The oligomeric form of the drug was used to overcome the challenge of drug aggregation and burst release when antibiotics are incorporated as free drug. Electrospinning parameters were optimized to obtain scaffolds with similar alignment and fiber diameter to non-drug loaded fibers. AO that diffused from the fibers was hydrolysed to release CF slowly and in a linear manner over the duration of the study, whereas scaffolds with CF at the same concentration but in free form showed a burst release within 1h with no further release throughout the study duration. Human gingival fibroblast (HGF) adhesion and spreading was dependent on the concentration and form the CF was loaded (AO vs. free CF), which was attributed in part to differences in scaffold surface chemistry. Surface segregation of AO was quantified using surface-resolved X-ray photoelectron spectroscopy (XPS). These findings are encouraging and support further investigation for the use of AO as a means of attenuating the rapid release of drug loaded into nanofibers. The study also demonstrates through quantitative measures that drug additives have the potential to surface-locate without phase separating from the fibers, leading to fast dissolution and differential fibroblast cell attachment.
authors.affiliation: Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Meghan Ee
authors.initials: ME
authors.lastname: Wright
authors.affiliation: Interface Biologics Inc., Toronto, Ontario, Canada.
authors.forename: Ian C
authors.initials: IC
authors.lastname: Parrag
authors.affiliation: Faculty of Dentistry, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Meilin
authors.initials: M
authors.lastname: Yang
authors.affiliation: Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada; Interface Biologics Inc., Toronto, Ontario, Canada; Faculty of Dentistry, University of Toronto, Toronto, Ontario, Canada. Electronic address: paul.santerre@utoronto.ca.
authors.forename: J Paul
authors.initials: JP
authors.lastname: Santerre
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology; D002448:Cell Adhesion; D002460:Cell Line; D002939:Ciprofloxacin / Q000737:chemistry* / Q000494:pharmacology; D003692:Delayed-Action Preparations; D016503:Drug Delivery Systems; D065546:Drug Liberation; D004355:Drug Stability; D005347:Fibroblasts / Q000187:drug effects / Q000502:physiology; D005881:Gingiva / Q000166:cytology; D006801:Humans; D057139:Nanofibers / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers; D011140:Polyurethanes / Q000737:chemistry*; D016966:Porphyromonas gingivalis / Q000187:drug effects; D054457:Tissue Scaffolds
chemical_list: D000900:Anti-Bacterial Agents; D003692:Delayed-Action Preparations; D011108:Polymers; D011140:Polyurethanes; C028914:triethylene glycol; D011092:Polyethylene Glycols; D002939:Ciprofloxacin
keywords: Antimicrobial; Drug release; Fibroblast; Nanofibers; Oligomers; Periodontal; Polyurethane