Multiaxial mechanical response and constitutive modeling of esophageal tissues: Impact on esophageal tissue engineering Gerhard Sommer a , Andreas Schriefl a , Georg Zeindlinger a , Andreas Katzensteiner a , Herwig Ainödhofer b , Amulya Saxena b , Gerhard A. Holzapfel a,c,⇑ a Institute of Biomechanics, Center of Biomedical Engineering, Graz University of Technology, Austria b Department of Pediatric- and Adolescent Surgery, Medical University of Graz, Austria c Department of Solid Mechanics, Royal Institute of Technology (KTH), Stockholm, Sweden article info Article history: Received 16 April 2013 Received in revised form 11 July 2013 Accepted 31 July 2013 Available online 8 August 2013 Keywords: Ovine esophagus Biomechanical behavior Uniaxial and biaxial tensile testing Extension-inflation testing Constitutive equation Residual strains abstract Congenital defects of the esophagus are relatively frequent, with 1 out of 2500 babies suffering from such a defect. A new method of treatment by implanting tissue engineered esophagi into newborns is cur- rently being developed and tested using ovine esophagi. For the reconstruction of the biological function of native tissues with engineered esophagi, their cellular structure as well as their mechanical properties must be considered. Since very limited mechanical and structural data for the esophagus are available, the aim of this study was to investigate the multiaxial mechanical behavior of the ovine esophagus and the underlying microstructure. Therefore, uniaxial tensile, biaxial tensile and extension-inflation tests on esophagi were performed. The underlying microstructure was examined in stained histological sections through standard optical microscopy techniques. Moreover, the uniaxial ultimate tensile strength and residual deformations of the tissue were determined. Both the mucosa-submucosa and the muscle layers showed nonlinear and anisotropic mechanical behavior during uniaxial, biaxial and inflation testing. Cyclical inflation of the intact esophageal tube caused marked softening of the passive esophagi in the circumferential direction. The rupture strength of the mucosa-submucosa layer was much higher than that of the muscle layer. Overall, the ovine esophagus showed a heterogeneous and anisotropic behavior with different mechanical properties for the individual layers. The intact and layer-specific multiaxial properties were characterized using a well-known three-dimensional micro- structurally based strain-energy function. This novel and complete set of data serves the basis for a better understanding of tissue remodeling in diseased esophagi and can be used to perform computer simula- tions of surgical interventions or medical-device applications. Ó 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved. 1. Introduction Esophageal atresia occurs in 1 out of 2500 live births [1]. It can occur in several anatomical variations: the most common form, with a percentage of 87%, is a blind esophageal pouch with a fistula between the trachea and the lower half of the esophagus. Other forms, like an isolated atresia or an isolated tracheoesophageal fistula, occur less often [2]. The standard method to repair esoph- ageal atresia is to connect the esophageal segments by primary anastomosis. However, this method is difficult to perform in cases with large gap atresias. A potentially viable alternative is the implantation of tissue engineered esophagi [3]. At this stage of development, ovine esophageal epithelial cells are seeded onto collagen scaffold sheets. These sheets are then wrapped around a sterile endotracheal tube to get a tubular geometry and subsequently implanted into the omentum of the lamb. After 8–10 weeks, they are removed for histological and morphological evaluations [3]. To ensure that tissue engineered esophagi show the same biomechanical behavior as their naturally grown counterparts, the behavior of the substitutes has to be investigated. Furthermore, the identification of the mechanical properties is a prerequisite for the proper evaluation of transmural stress distri- butions, which in turn is central to the understanding of esopha- geal physiology and pathophysiology [4,5]. These properties will also serve as a basis to assess remodeling processes of esophageal tissue in diseased states and to run computer simulations of surgical interventions and medical-device applications [5,6]. In general, the esophageal tube consists of multiple layers, which is typical for the whole gastrointestinal system. The most in- ner layer is the so-called mucosa, followed by the submucosa. The mucosa is a layer of epithelial cells, forming a continuous and homogeneous sheet. The submucosa is a broad zone of connective 1742-7061/$ - see front matter Ó 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.actbio.2013.07.041 ⇑ Corresponding author at: Institute of Biomechanics, Center of Biomedical Engineering, Graz University of Technology, Austria. E-mail address: holzapfel@tugraz.at (G.A. Holzapfel). Acta Biomaterialia 9 (2013) 9379–9391 Contents lists available at ScienceDirect Acta Biomaterialia journal homepage: www.elsevier.com/locate/actabiomat