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.

项目概要/摘要 先天性食管闭锁 (EA) 是一种潜在致命且相对常见的畸形，可导致 食管完全不连续。如果不及时治疗，患有这种疾病的新生儿将无法进食、窒息 依靠自己的唾液，最终死于慢性误吸继发的终末期呼吸衰竭 肺炎。虽然新生儿初次手术修复可以恢复两端之间的连续性 食管手术是一项挽救生命的手术，但对许多患者来说，该手术在技术上很困难，而且仍然令人担忧 术后并发症发生率很高，包括渗漏、复发性狭窄、瘘管、胃食管 反流和慢性吞咽困难。此外，在新生儿子集（10%）中，两者之间的差距 食管末端尺寸 >3 厘米（长间隙 EA），不可能通过手术连接末端，导致 由于需要进行高度病态的食管置换手术而住院数月 和/或其他复杂的操作。仍然迫切需要新的治疗策略来促进 这些新生儿的结局更好。我们的长期目标是开发基于再生医学的治疗方法 使用可改善吻合的 3D 打印 (3DP) 弹性材料的新生儿 EA 策略 伤口愈合并减少并发症。该项目的中心假设是植入 外部支架套管由弹性体聚甘油十二烷二酸酯 (PGD) 制成，并用 生物活性肽序列可以通过减少 EA 修复部位的食管吻合口愈合 吻合处的张力并增强细胞附着。该提案用两个具体的方法来检验这一假设 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 生物可吸收食管套的特性。在目标 2 中，研究人员将评估生物可吸收性 针对 EA 修复的新生儿大型动物模型中的吻合口愈合进行了优化的食管套管。完成 这些目标将推进非线性弹性可吸收弹性体的概念，作为一种新方法 通过细胞募集和纵向调节来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促进3DP设备的临床转化 儿科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 作为生成长间隙 EA 的全层节段组织的基底。