Degradation and Fatigue Behavior of 3D Printed Bioresorbable Tracheal Splints

摘要 气管支气管软化症（Tracheobonchomalacia，TBM）是一种先天性或获得性的气管和/或支气管畸形 软骨，表现为动态气道塌陷，呼吸困难，在严重的 病例，急性危及生命的事件。TBM患病率估计为1/2，200儿童1， 严重的病例可能导致死亡或需要气管切开术和通气2-3年， 给孩子和家庭带来沉重负担2，3。我们最近开发了一种生物可吸收的，病人 特定的3D打印聚己内酯（PCL）夹板治疗TBM，报告了第一例 新英格兰医学杂志4.随后三名患有危及生命的TBM的儿童获救 第一个孩子在手术后30个月仍然没有症状。 然而，夹板的长期临床应用需要进一步工程化以减少 除了了解夹板的吸收如何影响机械功能外， 气道的变形和重塑，以提高夹板的安全性和有效性。在 此外，FDA还要求根据我们的2014年8月22日 与FDA会面，启动人道主义器械豁免（HDE）的I期临床试验 批准我们将在体外和体内两个特定的目标来解决这些问题 临床前模型，约克郡猪。第一个目标将表征夹板降解， 体外和体内长达2年。第二个目标将使用这些数据来描述 夹板影响气道力学。

Abstract Tracheobonchomalacia (TBM) is a congenital or acquired deficiency of tracheal and/or bronchial cartilages that presents with dynamic airway collapse, respiratory difficulties, and, in severe cases, acute life-threatening events. TBM prevalence is estimated at 1 in 2,200 children1, and severe cases can result in death or require tracheostomy with ventilation for 2-3 years, a significant burden on the child and family2,3. We recently developed a bioresorbable, patient specific 3D printed polycaprolactone (PCL) splint to treat TBM, reporting the first case in the New England J. of Medicine4. Three subsequent children with life threatening TBM were saved with the splint and the first child continues to be asymptomatic 30 months post-surgery. However, long term clinical application of the splint requires further engineering to reduce the risk of fatigue failure in addition to understanding how resorption of the splint affects mechanical deformation and remodeling of the airway to improve safety and efficacy of the splint. In addition, the FDA also requires such data for regulatory approval based on our August 22, 2014 meeting with the FDA to initiate a phase I clinical trial for Humanitarian Device Exempt (HDE) approval. We will address these questions in two specific aims using both in vitro and in vivo preclinical model, the Yorkshire pig. The first aim will characterize splint degradation both in vitro and in vivo for up to 2 years. The second aim will use this data to characterize how the splint affects airway mechanics.