**1. Introduction**

The incidences of esophageal diseases like atresia, tracheoesophageal fistula, esophagitis, and even carcinoma rise rapidly worldwide. For example, Barrett's esophagus, a complica‐ tion of chronic gastroesophageal reflux disease (GERD), is a metaplasia of epithelial cells and often causes adenocarcinomas at a rate of approximately 1%. Among them, only 5–10% patients had chance to survive for 5 years if they do not receive treatment at the earliest stage [1]. The atresia of esophagus is a relatively common malformation occurred with a fre‐ quency of one in 2500 births [2]. Recently, more than 500,000 individuals are diagnosed with esophageal cancer each year with possibility of 850,000 by 2030 [3]. Esophageal cancer (EC) is a destructive disease. The treatment is usually tough and protracted, so as to inevitably reduce the patients' life quality, and may indirectly contribute to the mortality rate. Badly, the rate of esophageal cancer is 10–100 times higher in Iran, India, Northern China, and Southern Africa than the people in other place of the world [4]. The traditional therapies like

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2017 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

surgery, radiotherapy, or/and chemotherapy, and surgically replacing with stomach, colon, small intestine, etc. did not improve greatly the survival rate. In addition, esophagus donor is too rare to get autologous/allogeneic replacement from human body. A tissue‐engineered substitute with integrated structure and function is thought to be a promising and effective alternative for treating esophageal disease, which will eliminate the need to harvest replace‐ ment tissues from the patients' own body or other human body.

The esophagus is a muscular canal extending from pharynx to stomach and has functions to transport food and water from mouth to stomach. There are three types of cells, i.e., strati‐ fied squamous epithelial cells, fibroblasts, and smooth/skeletal muscle cells, which constitute four layers of this tissue, namely the mucosa, submucosa, muscularis externa, and adventitia. **Figure 1** shows the sketch and histological structure of human esophagus, in which a folding lumen is observed in a resting state (**Figure 1a**). The stratified squamous epithelial cells (E) compose the lumen epithelium that serves as a barrier or protective layer against mechanical stresses produced by food bolus. The epithelial cells are supported by the underlying base‐ ment membrane (**Figure 1b**, arrows). The topography of the basement membrane is a rugged and uneven stripe that consists of interwoven fibers. The diameters of these fibers were mea‐ sured to be from 28 to 165 nm with an average of 66 ± 24 nm. The pores displayed between fibers with unequal size (**Figure 1**c). The molecular components of the basement membrane

**Figure 1.** Overview and histological structure of esophagus (a). There are four tissue layers, i.e., mucosa containing epithelium (E), lamina propria and muscularis mucosae, submucosa (SM), muscularis externa consisting of two sub‐ layers of inner circular (IC) and outer longitudinal (OL) muscle, and adventitia in esophagus organ. The stratified squamous epithelial cells (E) lined the esophagus lumen (H&E staining). Cross‐section and topography of basement membrane were observed under transmission electron microscope (TEM) (b, c).

were detected to be collagen IV, laminin, entactin, and proteoglycans, mainly; among them collagen IV is slightly less than that of laminin but ∼50 times more than that of entactin, but the quantity of proteoglycans was ∼5 times more than that of entactin [5].

The muscle component in esophagus is responsible for motor function via peristalsis longitu‐ dinally and circumferentially. It consists of striated skeletal muscle in upper third, mixture of skeletal and smooth muscle in the middle third, and pure smooth muscle in the lower third. The muscle exhibits a bilaminar arrangement. The endo‐circular and exo‐longitudinal myo‐ fibrils (**Figure 1a**, IC and OL) are packed bilaminarly in order to propel the swallowing food and water into stomach through sequential contraction of the circular muscles via occlud‐ ing the esophagus lumen, and longitudinal muscle by shortening the duct and enlarging the lumen, or enhancing the fibril density of the circular muscle, which in turn improves the contracting efficiency of the circular muscle [6–8].

Tissue engineering is an interdisciplinary field that applies the principles of engineering and life sciences toward the development of biological substitutes that restore, maintain, or improve tissue function, proposed by Langer and Vacanti. Scaffolds, cells, and their combina‐ tion are the main three topics of tissue engineering research. Material is the necessary substra‐ tum in scaffold fabrication. There are various types of materials that have been developed as scaffold matrices to constitute esophagus tissue, for example, resorbable substances, decellu‐ larized matrices, acellular patches, and the composites from natural and/or synthesized poly‐ mers. Among them, a number of tissue‐derived extracellular matrix (ECM) like decellularized urinary bladder submucosa, gastric acellular matrix, aortal acellular matrix, acellular dermal grafts, and decellularized esophagus have been much investigated for the applications as esophagus replacement. Some have also been tested for healing injury of esophagus in ani‐ mal models or even human trials. Alternatively, synthesized and/or natural materials or their composites also attracted more and more attentions in researches of tissue engineering and regenerative medicine. Refs. [9, 10] reported that poly(glycolic acid) (PGA) and silicone with collagen coating were applied to constitute tubular scaffold. Small intestinal submucosa (SIS) was used as the replacement of tubular organs, for example, esophagus and large‐diameter vascular grafts, as literature reports. Nonetheless, the complications or postoperative prob‐ lems like inflammation, leakage, stenosis, and extrusion in long‐term implantation are still presented when the materials or scaffolds are implanted into bodies.
