3D printed bioresorbable sleeve device for esophageal atresia repair

用于食管闭锁修复的3D打印生物可吸收套筒装置

• 批准号: 10710202
• 负责人: Scott J Hollister
• 金额: $ 24.22万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-26 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10710202
• 关键词: 3D Print; Affect; Anastomosis - action; Animal Model; Aspiration Pneumonia; Autologous; Biocompatible Materials; Biomechanics; Cell-Matrix Junction; Cells; Child; Childhood; Choking; Chronic; Clinical; Complex; Complication; Computer Models; Congenital Abnormality; Data; Deglutition; Deglutition Disorders; Development; Devices; Distal; Eating; Elasticity; Elastomers; Endothelial Cells; Esophageal Atresia; Esophageal Tissue; Esophagus; Etiology; Excision; Extracellular Matrix; Finite Element Analysis; Fistula; Gastroesophageal reflux disease; Generations; Goals; Growth; Hospitalization; Implant; Intestines; Left; Length; Life; Measures; Mechanics; Mesenchymal; Natural regeneration; Neonatal; Neonatal Intensive Care Units; Newborn Infant; Operating Rooms; Operative Surgical Procedures; Outcome; Patients; Postoperative Complications; Postoperative Period; Procedures; Property; Public Health; Publishing; Quality of life; Radial; Recurrence; Regenerative Medicine; Research Personnel; Respiratory Failure; Saliva; Secondary to; Site; Study models; Surgeon; Surgical sutures; Technology; Testing; Thick; Time; Tissues; Trachea; Tracheoesophageal Fistula; Vascularization; biomaterial compatibility; clinical translation; comparison control; design; elastomeric; experience; experimental study; healing; implantation; improved; in vivo; malformation; mechanical properties; neonate; novel; novel strategies; operation; polyglycerol; protein aminoacid sequence; prototype; reconstruction; recruit; repaired; scaffold; treatment strategy; wound; wound healing

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.

项目摘要/摘要 先天食道闭锁（EA）是一种潜在的致命且相对常见的畸形，导致 食道完全不连续。未经治疗，这种情况的新生儿无法进食，cho 用自己的唾液，最终死于终点呼吸道衰竭，继发于慢性志向 肺炎。尽管新生儿原发性手术修复，它恢复了两端的连续性 食道是一种挽救生命的手术，在许多患者中，该过程在技术上很困难，并且仍然很生气 术后并发症率很高，包括泄漏，经常性狭窄，瘘管，胃食管 反流和慢性吞咽困难。此外，在新生儿的一部分（10％）中，其中两者之间的差距 食管末端的测量> 3厘米（长距离EA），无法手术连接末端，导致 由于需要执行高病态的食管置换程序，因此住院数月 和/或其他复杂操作。对于可以促进的新型治疗策略仍然存在至关重要的需求 这些新生儿的结果更好。我们的长期目标是开发基于再生医学的治疗 使用3D打印（3DP）弹性材料的新生儿的策略，可以改善吻合 伤口愈合并减少并发症。该项目的核心假设是植入 外部支架套筒，由弹性剂，多甘油甘油糖酸盐（PGD）制成，并与 生物活性肽序列可以通过还原来改善EA修复部位的食管吻合疗法 吻合处的张力并增强细胞附着。该提案用两个特定的 目标。在AIM 1中，调查人员将确定脚手架设计如何影响降解和生物力学 可生物吸收的食管套的特性。在AIM 2中，调查人员将评估可生物吸收性 在新生儿大型EA修复模型中，可针对吻合式愈合进行优化的食管套。完成 这些目标将提高非线性弹性可吸收弹性体的概念，以此作为一种新颖的方法 通过纵向调节和调节，调节局部食管组织微环境 和径向力。此外，我们预计这些实验将有助于3DP设备的临床翻译 小儿外科医生在手术室使用的技术，利用我们的患者临床经验 气管设备。最后，我们的方法还将为弹性设备的开发奠定基础 作为长间隙EA的全厚度分段组织的产生的底物。