Development of a new tissue-engineered sheet for reconstruction of the stomach.

ABSTRACT

We have developed tissue-engineered digestive tracts composed of collagen scaffold and an inner silicon sheet and successfully used it to repair defects in parts of the esophagus, stomach, and small intestine. However, some improvements were demanded for clinical usage because the silicon sheet presented technical difficulties for suturing and endoscopic removal. New tissue-engineered sheet (New-sheet) was composed of a single-piece and reinforced collagen scaffold with biodegradable copolymer. One beagle dog was used to evaluate whether New-sheet could withstand suturing in comparison with native digestive tracts using a tensile tester. Seven beagle dogs had a 5-cm circular defect created in the stomach. New-sheet soaked with autologous peripheral blood or bone marrow aspirate was sutured to the gastric wall. Endoscopic, histological, and immunohistochemical assessment was performed to evaluate regeneration of the stomach up to 16 weeks. Tensile strength testing showed that the mucosal side of New-sheet had strength almost equivalent to the mucosa of the esophagus (P = 0.61). Endoscopically, regeneration of the mucosa started from the circumference after 4 weeks, but a small linear ulcer was still evident at 16 weeks. The regenerated stomach shrank by 60-80% of its original size and histologically showed villous mucosa and underlying dense connective tissue. Immunohistochemically, the regenerated area expressed alpha-smooth-muscle actin but was negative for basic calponin, irrespective of the source of soaked blood. New-sheet shows sufficient strength for suturing, no dehiscence, and better biocompatibility for clinical use, although further examination will be necessary to create a functional digestive tract.