Human-sized lung decellularization using a novel bioreactor system

IntroductionDecellularized whole lungs provide a suitable platform for culturing patient-specific cells for developing substitutable functional lungs to cure end-stage patients with pulmonary diseases such as COPD. In order to fill the gaps between the laboratory and clinical implementation of regenerated lungs, efficient bioreactor systems for producing human-sized lung scaffolds are required.ObjectivesThe goal of this study was to develop a bioreactor system to achieve consistent decellularized human-sized lungs.MethodsA 20-liter chamber with a custom-designed cap was modified to contain a human-sized lung, providing necessary connections to trachea and pulmonary artery via embedded ports. This chamber was used to decellularize a sheep lung with an SDS-based protocol. The decellularization was performed up to 24 hours at the perfusion rate of 1.1-1.4 L/min for different stages.ResultsThe architecture of native and decellularized lungs was analyzed with hematoxylin and eosin (H&E) staining and scanning electron microscopy (SEM). Removal of nuclear material was proved by H&E staining; also, SEM imaging demonstrated total removal of cells and preserved structural architecture.ConclusionThis bioreactor system allows for convenient and consistent decellularization of human-sized lungs by decreasing hand involvement and facilitating the application of different protocols. Therefore, this bioreactor can accelerate steps toward clinical implementation of lung regeneration.

Keywords:

Bioreactor , Human-sized lungs , Decellularization , Tissue engineering , Regenerative medicine