Approximately 740 million symptomatic patients are affected by otitis media every year.Being an inflammatory disease affecting the middle ear,it is one of the primary causes of tympanic membrane(TM)perforations,often ...Approximately 740 million symptomatic patients are affected by otitis media every year.Being an inflammatory disease affecting the middle ear,it is one of the primary causes of tympanic membrane(TM)perforations,often resulting in impaired hearing abilities.Antibiotic therapy using broad-spectrum fluoroquinolones,such as ciprofloxacin(CIP),is frequently employed and considered the optimal route to treat otitis media.However,patients often get exposed to high dosages to compensate for the low drug concentration reaching the affected site.Therefore,this study aims to integrate tissue engineering with drug delivery strategies to create biomimetic scaffolds promoting TM regeneration while facilitating a localized release of CIP.Distinct electrospinning(ES)modalities were designed in this regard either by blending CIP into the polymer ES solution or by incorporating nanoparticles-based co-ES/electrospraying.The combination of these modalities was investigated as well.A broad range of release kinetic profiles was achieved from the fabricated scaffolds,thereby offering a wide spectrum of antibiotic concentrations that could serve patients with diverse therapeutic needs.Furthermore,the incorporation of CIP into the TM patches demonstrated a favorable influence on their resultant mechanical properties.Biological studies performed with human mesenchymal stromal cells confirmed the absence of any cytotoxic or anti-proliferative effects from the released antibiotic.Finally,antibacterial assays validated the efficacy of CIP-loaded scaffolds in suppressing bacterial infections,highlighting their promising relevance for TM applications.展开更多
基金funded by the 4NanoEARDRM project,under the frame of EuroNanoMed III,an ERA-NET Cofund scheme of the Horizon 2020 Research and Innovation Framework Programme of the European Commission,the Netherlands Organization for Scientific Research(NWO,grant number OND1365231)German Federal Ministry of Education and Research(BMBF,grant number 13XP5061A)the Italian Ministry of Education,University and Research(MIUR,grant number B56H18000140001).
文摘Approximately 740 million symptomatic patients are affected by otitis media every year.Being an inflammatory disease affecting the middle ear,it is one of the primary causes of tympanic membrane(TM)perforations,often resulting in impaired hearing abilities.Antibiotic therapy using broad-spectrum fluoroquinolones,such as ciprofloxacin(CIP),is frequently employed and considered the optimal route to treat otitis media.However,patients often get exposed to high dosages to compensate for the low drug concentration reaching the affected site.Therefore,this study aims to integrate tissue engineering with drug delivery strategies to create biomimetic scaffolds promoting TM regeneration while facilitating a localized release of CIP.Distinct electrospinning(ES)modalities were designed in this regard either by blending CIP into the polymer ES solution or by incorporating nanoparticles-based co-ES/electrospraying.The combination of these modalities was investigated as well.A broad range of release kinetic profiles was achieved from the fabricated scaffolds,thereby offering a wide spectrum of antibiotic concentrations that could serve patients with diverse therapeutic needs.Furthermore,the incorporation of CIP into the TM patches demonstrated a favorable influence on their resultant mechanical properties.Biological studies performed with human mesenchymal stromal cells confirmed the absence of any cytotoxic or anti-proliferative effects from the released antibiotic.Finally,antibacterial assays validated the efficacy of CIP-loaded scaffolds in suppressing bacterial infections,highlighting their promising relevance for TM applications.