3D printed bioresorbable sleeve device for esophageal atresia repair

项目总结/摘要 先天性食管闭锁（EA）是一种潜在的致命性和相对常见的畸形， 食管完全不连续。如果不及时治疗，患有这种疾病的新生儿无法进食，窒息 并最终死于慢性吸入引起的终末期呼吸衰竭 肺炎虽然新生儿一期手术修复，恢复了两端之间的连续性， 食管，是一个挽救生命的手术，该程序是技术上困难的许多患者，仍然充满了 术后并发症发生率高，包括泄漏、复发性狭窄、瘘、胃食管 反流和慢性吞咽困难。此外，在一个新生儿子集（10%）中，两者之间的差距 食管末端测量>3 cm（长间隙EA），手术连接末端是不可能的，导致 由于需要进行高度病态的食管置换手术， 和/或其他复杂操作。仍然迫切需要新的治疗策略， 更好的结果。我们的长期目标是开发基于再生医学的治疗方法 使用3D打印（3DP）弹性材料治疗EA新生儿的策略，可改善吻合 减少并发症。该项目的中心假设是， 由弹性体聚甘油十二烷二酸酯（PGD）制成的外部支架套管， 生物活性肽序列可以通过减少食管吻合口愈合， 吻合处的张力和增强细胞附着。该提案用两个具体的假设来检验这一假设。 目标。在目标1中，研究人员将确定支架设计如何影响降解和生物力学 生物可吸收食管袖套的性能。在目标2中，研究者将评价生物可吸收性 在EA修复的新生大动物模型中优化吻合口愈合的食管袖套。完成 这些目标将推进非线性弹性可吸收弹性体的概念，作为一种新的方法， 通过细胞募集和调节食管组织的纵向微环境， 和径向力。此外，我们预计这些实验将促进3DP设备的临床转化 儿童外科医生在手术室使用的技术，利用我们的患者临床经验， 气管装置最后，我们的方法也将为弹性体装置的开发奠定基础 作为用于长间隙EA的全层节段组织的产生的基底。

Project Summary/Abstract Congenital esophageal atresia (EA) is a potentially lethal and relatively common malformation that results in a complete discontinuity of the esophagus. Left untreated, neonates with this condition are unable to eat, choke on their own saliva, and eventually die from end-stage respiratory failure secondary to chronic aspiration pneumonia. Although neonatal primary surgical repair, which restores continuity between the two ends of the esophagus, is a life-saving operation, the procedure is technically difficult in many patients and remains fraught with a high rate of postoperative complications, including leaks, recurrent strictures, fistulae, gastroesophageal reflux, and chronic dysphagia. Moreover, in a subset of newborns (10%) where the gap between the two esophageal ends measures >3 cm (long-gap EA), connecting the ends surgically is impossible, resulting in months of hospitalization because of the need to perform highly morbid esophageal replacement procedures and/or other complex operations. There remains a critical need for novel treatment strategies that can facilitate better outcomes in these newborns. Our long-term goal is to develop regenerative medicine-based treatment strategies for newborns with EA using 3D printed (3DP) elastomeric materials that can improve anastomotic wound healing and decrease complications. The central hypothesis of this project is that the implantation of an external scaffold sleeve made from the elastomer, poly-glycerol-dodecanedioate (PGD), and functionalized with bioactive peptide sequences can improve esophageal anastomotic healing at the EA repair site by reducing tension at the anastomosis and enhancing cell attachment. This proposal tests this hypothesis with two specific aims. In Aim 1, the investigators will determine how scaffold design affects the degradation and biomechanical properties of bioresorbable esophageal sleeves. In Aim 2, the investigators will evaluate bioresorbable esophageal sleeves optimized for anastomotic healing in a neonatal large animal model of EA repair. Completion of these Aims will have advanced the concept of nonlinear elastic resorbable elastomers as a novel approach to modulate the local esophageal tissue microenvironment through cell recruitment and modulation of longitudinal and radial forces. In addition, we anticipate that these experiments will facilitate clinical translation of 3DP device technologies for use by pediatric surgeons in the operating room, leveraging our patient clinical experience with tracheal devices. Finally, our approach will also have set the stage for the development of elastomeric devices as a substrate for the generation of full-thickness segmental tissue for long-gap EA.