Recent frontiers in biofabrication for respiratory tissue engineering

Respiratory tissue engineering offers a robust framework for studying cell-cell and host-pathogen interactions in a tissue-like environment and offers a platform for studying lung tissue regeneration and disease mechanisms. However, the challenge of replicating dynamic three-dimensional (3D) microenvironments is a huge obstacle with existing technology. Current animal models and two-dimensional cell culture models do not replicate in vivo conditions seen in human lungs, thus research utilizing these techniques often fails to help alleviate the global burden of respiratory diseases. Respiratory tissue engineering has been drawing significant attention over the past decade. Particularly with the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), many inspiring developments and advances have been reported. This review presents the recent advances of respiratory tissue engineering focusing on 3D bioprinting, organ-on-a-chip, and organoid technologies. It also provides an overview of recent attempts to integrate biomechanical stimulus with the aim of improving the integrity of 3D constructs and enhancing cellular propagation. This review addresses the challenges inherent in existing 3D respiratory models and discusses the future prospects of research in this field, urging continuing innovation and investment toward the success of respiratory tissue engineering and increasing clinical relevance.