Anand Shivesh, Fusco Alessandra, Günday Cemre, Günday-Türeli Nazende, Donnarumma Giovanna, Danti Serena, Moroni Lorenzo, Mota Carlos
Department of Complex Tissue Regeneration, MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, 6229 ER, Maastricht, the Netherlands.
Interuniversity National Consortiums of Materials Science and Technology (INSTM), 50121, Firenze, Italy.
Bioact Mater. 2024 Apr 24;38:109-123. doi: 10.1016/j.bioactmat.2024.04.001. eCollection 2024 Aug.
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.
每年约有7.4亿有症状的患者受中耳炎影响。作为一种影响中耳的炎症性疾病,它是鼓膜穿孔的主要原因之一,常导致听力受损。使用广谱氟喹诺酮类抗生素进行治疗,如环丙沙星(CIP),是治疗中耳炎常用且被认为是最佳的途径。然而,患者常常需要接受高剂量药物治疗,以弥补到达感染部位的药物浓度较低的问题。因此,本研究旨在将组织工程与药物递送策略相结合,制备仿生支架,促进鼓膜再生,同时实现环丙沙星的局部释放。在这方面,通过将环丙沙星混入聚合物静电纺丝溶液或采用基于纳米颗粒的共静电纺丝/电喷雾技术,设计了不同的静电纺丝模式。还研究了这些模式的组合。从制备的支架获得了广泛的释放动力学曲线,从而提供了可满足不同治疗需求患者的多种抗生素浓度。此外,将环丙沙星掺入鼓膜贴片对其最终的力学性能显示出有利影响。用人间充质基质细胞进行的生物学研究证实,释放的抗生素不存在任何细胞毒性或抗增殖作用。最后,抗菌试验验证了载有环丙沙星的支架在抑制细菌感染方面的有效性,突出了其在鼓膜应用方面的潜在价值。