Assessment of Esophageal Reconstruction via Bioreactor Cultivation of a Synthetic Scaffold in a Canine Model
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Objectives. Using tissue-engineered materials for esophageal reconstruction is a technically challenging task in animals thatrequires bioreactor training to enhance cellular reactivity. There have been many attempts at esophageal tissue engi-neering, but the success rate has been limited due to difficulty in initial epithelialization in the special environment ofperistalsis. The purpose of this study was to evaluate the potential of an artificial esophagus that can enhance the re-generation of esophageal mucosa and muscle through the optimal combination of a double-layered polymeric scaf-fold and a custom-designed mesenchymal stem cell-based bioreactor system in a canine model. Methods. We fabricated a novel double-layered scaffold as a tissue-engineered esophagus using an electrospinning tech-nique. Prior to transplantation, human-derived mesenchymal stem cells were seeded into the lumen of the scaffold,and bioreactor cultivation was performed to enhance cellular reactivity. After 3 days of cultivation using the bioreac-tor system, tissue-engineered artificial esophagus was transplanted into a partial esophageal defect (5×3 cm-long re-section) in a canine model. Results. Scanning electron microscopy (SEM) showed that the electrospun fibers in a tubular scaffold were randomly andcircumferentially located toward the inner and outer surfaces. Complete recovery of the esophageal mucosa was con-firmed by endoscopic analysis and SEM. Esophagogastroduodenoscopy and computed tomography also showed thatthere were no signs of leakage or stricture and that there was a normal lumen with complete epithelialization. Signif-icant regeneration of the mucosal layer was observed by keratin-5 immunostaining. Alpha-smooth muscle actin im-munostaining showed significantly greater esophageal muscle regeneration at 12 months than at 6 months. Conclusion. Custom-designed bioreactor cultured electrospun polyurethane scaffolds can be a promising approach foresophageal tissue engineering.
Abstract
Objectives. Using tissue-engineered materials for esophageal reconstruction is a technically challenging task in animals thatrequires bioreactor training to enhance cellular reactivity. There have been many attempts at esophageal tissue engi-neering, but the success rate has been limited due to difficulty in initial epithelialization in the special environment ofperistalsis. The purpose of this study was to evaluate the potential of an artificial esophagus that can enhance the re-generation of esophageal mucosa and muscle through the optimal combination of a double-layered polymeric scaf-fold and a custom-designed mesenchymal stem cell-based bioreactor system in a canine model. Methods. We fabricated a novel double-layered scaffold as a tissue-engineered esophagus using an electrospinning tech-nique. Prior to transplantation, human-derived mesenchymal stem cells were seeded into the lumen of the scaffold,and bioreactor cultivation was performed to enhance cellular reactivity. After 3 days of cultivation using the bioreac-tor system, tissue-engineered artificial esophagus was transplanted into a partial esophageal defect (5×3 cm-long re-section) in a canine model. Results. Scanning electron microscopy (SEM) showed that the electrospun fibers in a tubular scaffold were randomly andcircumferentially located toward the inner and outer surfaces. Complete recovery of the esophageal mucosa was con-firmed by endoscopic analysis and SEM. Esophagogastroduodenoscopy and computed tomography also showed thatthere were no signs of leakage or stricture and that there was a normal lumen with complete epithelialization. Signif-icant regeneration of the mucosal layer was observed by keratin-5 immunostaining. Alpha-smooth muscle actin im-munostaining showed significantly greater esophageal muscle regeneration at 12 months than at 6 months. Conclusion. Custom-designed bioreactor cultured electrospun polyurethane scaffolds can be a promising approach foresophageal tissue engineering.
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