Abstract：
Endotracheal Tubes (ETTs) maintain and secure a patent airway; however, prolonged intubation often results in unintended injury to the mucosal epithelium and inflammatory sequelae which complicate recovery. ETT design and materials used have yet to adapt to address intubation associated complications. In this study, a composite coating of electrospun polycaprolactone (PCL) fibers embedded in a four-arm polyethylene glycol acrylate matrix (4APEGA) is developed to transform the ETT from a mechanical device to a dual-purpose device capable of delivering multiple therapeutics while preserving coating integrity. Further, the composite coating system (PCL-4APEGA) is capable of sustained delivery of dexamethasone from the PCL phase and small interfering RNA (siRNA) containing polyplexes from the 4APEGA phase. The siRNA is released rapidly and targets smad3 for immediate reduction in pro-fibrotic transforming growth factor-beta 1 (TGFϐ1) signaling in the upper airway mucosa as well as suppressing long-term sequelae in inflammation from prolonged intubation. A bioreactor was used to study mucosal adhesion to the composite PCL-4APEGA coated ETTs and investigate continued mucus secretory function in ex vivo epithelial samples. The addition of the 4APEGA coating and siRNA delivery to the dexamethasone delivery was then evaluated in a swine model of intubation injury and observed to restore mechanical function of the vocal folds and maintain epithelial thickness when observed over 14 days of intubation. This study demonstrated that increase in surface lubrication paired with surface stiffness reduction significantly decreased fibrotic behavior while reducing epithelial adhesion and abrasion.
摘要：
气管内管（ETT）维持和保护气道通畅；但是，长时间的插管通常会导致粘膜上皮的意外损伤和炎症后遗症，从而使康复复杂化。ETT设计和使用的材料尚未适应于解决插管相关的并发症。在这项研究中,开发了嵌入四臂聚乙二醇丙烯酸酯基质(4APEGA)中的电纺聚己内酯(PCL)纤维的复合涂层,以将ETT从机械装置转变为能够递送多种治疗剂同时保持涂层完整性的双重用途装置。Further,复合涂层系统（PCL-4APEGA）能够从PCL相持续递送地塞米松，并从4APEGA相持续递送含有多聚复合物的小干扰RNA（siRNA）。siRNA迅速释放并靶向smad3，以立即减少上气道粘膜中的促纤维化转化生长因子β1（TGF-1）信号传导，并抑制长期插管引起的炎症后遗症。使用生物反应器研究了对复合PCL-4APEGA包被的ETT的粘膜粘附，并研究了离体上皮样品中持续的粘液分泌功能。然后在插管损伤的猪模型中评估将4APEGA涂层和siRNA递送添加到地塞米松递送中,并且当在插管的14天观察时观察到恢复声带的机械功能并保持上皮厚度。这项研究表明，表面润滑的增加与表面刚度的降低相结合，显着降低了纤维化行为，同时减少了上皮的粘附和磨损。
