Biofabrication of esophageal grafts in the treatment of benign stenosis

The esophagus is a muscular-mucosal organ that connects the pharynx to the stomach. It is vulnerable to various pathologies, including stenosis, a narrowing of the organ's diameter. Stenosis can be malignant or benign, with the latter being the most common, often caused by peptic injury from gastroesophageal reflux disease (GERD). The gold standard to treat benign strictures is the execution of dilation procedures which are mostly effective, safe and easy to perform. Different types of dilators are available, including balloon and mechanical dilators that can be inserted with or without a guide. Although dilatation is generally safe, the most significant complication is perforation, with a risk of 0.1–0.4%. The disadvantage is that recurrent stenosis can happen in up to 35% of all patients. To overcome relapse, three different stents have been used over the last century to keep the lumen open. Self-expanding metallic stents (SEMS) placement is another treatment strategy for esophageal strictures. However, metal stents can lead to serious long-term complications such as cancer growth, migration, and the reaction of hyperplastic tissue. To address these issues, self-expanding plastic stents (SEPS) were developed, which offer two significant advantages over metallic stents: the lack of the metal grid and the availability of a coating silicone layer minimizing tissue hyperplasia and enabling better stent. SEPS also have a high expansive power that reduces migration, while still providing effective dilation of the stenotic area. The major drawback of polymeric stents is the high migration degree. An attractive alternative to avoid migration might be the utilization of biodegradable stents. Moreover, the use of specific biomaterials could induce tissue regeneration because of its uncovered design, which enables the stent to embed in the esophageal lining and greatly decreases the migration rate. However, different studies have shown the potential threads of tissue hyperplasia. Our efforts were focused on the development of a double-layer esophageal graft with an inner diameter that mimics the native tissue (i.e. 20 mm) resistant to kinking, buckling, and migration. To achieve this, we designed a structure consisting of 1 mm thick rings, made of Tecoflex EG 60 D, arranged at specific intervals. We added another concentric layer of Tecoflex SG 85 A on top of the rings, forming a robust and resilient double-layered structure. We hypothesized that the rings, being made of stiffer material, would play a critical role in providing structural support to the graft by exerting an outward radial force that allows the positioning and stability of the graft within the stricture. Using Solidworks, we designed the structure that was 30 mm long and with an overall thickness of 1500µm, then it was analyzed for FEM analysis in Abaqus. Three structures were investigated with the rings spaced 1, 3, and 5 mm apart, simulating the passage of the food bolus under physiological conditions to the stresses that the graft would be subjected to. As the distance between the rings increases, the Von Mises stress decreases. We understood that our scaffold is able to withstand the stresses induced by the passage of food bolus. Furthermore, we conducted buckling and migration tests both numerically and experimentally for all three structures, using Abaqus and the uniaxial device, respectively. Future work will be focused on implementing the graft to meet native tissue structure-function.