Fabrication of multi-layer complex tubular construct using dragging technique for esophageal regeneration

Abstract

Tracheoesophageal fistula (TEF) / Esophageal atresia (EA) is one of the most common gastrointestinal birth defects. The incidence rate of TER/EA is approximately 1 to 4,000 live births. However, no definite cause has been identified. In addition, the treatment of diseases such as esophageal cancer, tumors and the like may require esophagectomy and reconstruction. Currently, esophageal reconstruction method use autografts tissue such as the stomach, intestine and colon. However, the substitution of autograft tissue does not completely restore the function of the esophagus and there is also the risk of complications. Therefore, the development of tissue engineered structures that can provide alternatives to esophageal reconstruction can be important clinical applications. Most of the conduit-type structure being studied are fabricated using electrospinning technology on tubular structures. However, conduits manufactured by e-spinning technology are not capable of forming freeform, multi-layer structure and have poor mechanical performance. In this study, we developed a dragging technique to fabricate a freeform and multi-layer tubular structure. The dragging technique can control the viscosity of the polymer, the design of dragging structure and the various printing parameters to fabricate the structure. Using this dragging technique, the multi-layer complex tubular construct was fabricated by mimic the mucosal, submucosal and smooth muscle layer of the esophagus. Each later of the tubular construct was printed with decellularized esophageal tissue-derived bioinks. Tubular construct functionality was evaluated by finite element analysis and mechanical properties were evaluated by the tensile test. Animal experiments using rabbits will be conducted in the future.