3D printed bioresorbable sleeve device for esophageal atresia repair

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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.