Functional closure of visceral pleural defects by autologous tissue engineered cell sheets☆

Abstract
Objective: The occurrence of intraoperative air leaks is an unavoidable complication during pulmonary surgeries. However, current surgical methods are generally ineffective in closing these visceral pleural defects, resulting in a decreased quality of life for patients. Here, we examined novel tissue engineered cell sheets for the closure of pleural defects in a porcine model. Methods: Skin biopsies were harvested from juvenile swine and tissue sheets composed of dermal fibroblasts were created using ex vivo culture on temperature-responsive dishes. After creating a visceral pleural injury model, the tissue engineered autologous dermal fibroblast sheets were transplanted directly to the defects without the use of sutures or additional adhesive agents, such as fibrin glue. Results: The tissue engineered autologous dermal fibroblast sheets attached directly to the lung surface providing an immediate seal against up to 25 cm H2O of airway pressure. Four weeks after transplantation, the dermal fibroblast sheets remained present on the pleural surface, providing permanent closure. The dermal fibroblast sheets were also responsive to changes in lung volume due to mechanical ventilation. No recurrences of air leaks were observed throughout the follow-up period. Conclusions: This study presents the development of an effective sealant for visceral pleural defects using autologous cells that have the flexibility to respond to expansion and contraction during respiration.