Tissue engineering of the gastroesophageal junction

The gastroesophageal junction has been of clinical interest for some time due to its important role in preventing reflux of caustic stomach contents upward into the esophagus. Failure of this role has been identified as a key driver in gastroesophageal reflux disease, cancer of the lower esophagus, and aspiration-induced lung complications. Due to the large population burden and significant morbidity and mortality related to reflux barrier dysfunction, there is a pressing need to develop tissue engineering solutions which can replace diseased junctions. While good progress has been made in engineering the bodies of the esophagus and stomach, little has been done for the junction between the two. In this review, we discuss pertinent topics which should be considered as tissue engineers begin to address this anatomical region. The embryological development and adult anatomy and histology are discussed to provide context about the native structures which must be replicated. The roles of smooth muscle structures in the esophagus and stomach, as well as the contribution of the diaphragm to normal anti-reflux function are then examined. Finally, engineering considerations including mechanics and current progress in the field of tissue engineering are presented.