Negative Pressure Cell Delivery Augments Recellularization of Decellularized Lungs

Abstract

For end-stage lung disease, lung transplantation remains the only treatment but is limited by the availability of organs. Production of bioengineered lungs via recellularization is an alternative but is hindered by inadequate repopulation. We present a cell delivery method via the generation of negative pressure. Decellularized lungs were seeded with human bronchial epithelial cells using gravity-based perfusion or negative pressure (via air removal). After delivery, lungs were maintained in static conditions for 18 h, and cell surface coverage was qualitatively assessed using histology and analyzed by subjective scoring and an image analysis software. Negative pressure seeded lungs had higher cell surface coverage area, and this effect was maintained following 5 days of culture. Enhanced coverage via negative pressure cell delivery was also observed when vasculature seeded with endothelial cells. Our findings show that negative pressure cell delivery is a superior approach for the recellularization of the bioengineered lung.

Impact statement

New strategies are required to overcome the shortage of organ donors for lung transplantation. Recellularization of acellular biological scaffolds is an exciting potential alternative. Adequate recellularization, however, remains a significant challenge. This proof of concept study describes a novel cell delivery approach, which further enhances the recellularization of decellularized lungs. Organs seeded and cultured with this method possess higher cell surface coverage and number compared to those seeded via traditional gravity-based perfusion approaches.