The oesophagus is a cylindrical organ with a collapsed lumen and mucosal folds. The mucosal folding may serve to advance the function of the oesophagus, i.e. the folds have a major influence on the flow of air and bolus through the oesophagus. Experimental studies have demonstrated oesophageal mucosal folds in the noload state. This indicates that mucosal buckling must be considered in the analysis of the mechanical reference state since the material stiffness drops dramatically after tissue collapse. Most previous work on the oesophageal zero-stress state and mucosal folding has been experimental. However, numerical analysis offers a promising alternative approach, with the additional ability to predict the mucosal buckling behaviour and to calculate the regional stress and strain in complex structures. A numerical model used for describing the mechanical behaviour of the mucosal-folded, threelayered, two-dimensional oesophageal model is reviewed. GIOME models can be used in the future to predict the tissue function physiologically and pathologically.
EXPERIMENTAL AND MODELING
APPROACHES TO THE ZERO-STRESS STATE AND MUCOSAL BUCKLINGNew computational models for describing the gastrointestinal (GI) tract mechanical behaviour precisely are a GIOME approach for bioengineering tissue modelling. The zero-stress state provides a standardized reference state for describing the mechanical response to external loading [1][2][3][4] . A large number of studies have been published on the zero-stress state of the cardiovascular and GI systems. The zero-stress state in soft biological tissues can be obtained by an experiment where tissue rings are cut radically, opening up into sectors. The angle subtended by the open ring, referred to as the opening angle, is used as a measure of the residual stress present in the intact ring of the tissue [2] . However, recent studies on multi-layered organs such as blood vessels and the GI tract indicate that the zero-stress state differs between layers and that a stress jump exists between the layers [5][6][7][8][9][10][11] . Thus, the true stressfree configuration for a multi-layered model is at least a twice cut tissue ring; one circumferential cut for layer separation and one radial cut in each layer to generate a true stress-free state.Longitudinal mucosal folds exist throughout the length of the oesophagus. It was originally believed that the folding was caused by the contraction of the muscle layer in an in vivo state [12] . However, the folds appear even at the no-load state [5] . Hence, additional tension caused by the compressed mucosa-submucosal layer exists in the muscle layer at the no-load state. Furthermore, the mucosal layer is not perfectly elastic, its circumferential length cannot decrease to zero, thus the tension in the muscle layer will collapse the mucosal layer [12] . Therefore, the buckling feature of the oesophagus must be accounted for in a reference state analysis since the material stiffness drops dramatically after tissue collapse.In the airways it ha...