Rationale: Much recent interest in lung bioengineering by pulmonary investigators, industry, and the organ transplant field has seen a rapid growth of bioreactor development ranging from the microfluidic scale to the human-sized whole lung systems. Comprehension of the findings from these models is needed to provide the basis for further bioreactor development. Objective: The goal was to comprehensively review the current state of bioreactor development for the lung. Methods: A search using PubMed was done for published, peer-reviewed papers using the keywords “lung” AND “bioreactor” or “bioengineering” or “tissue engineering” or “ex vivo perfusion”. Main Results: Many new bioreactors ranging from the microfluidic scale to the human-sized whole lung systems have been developed by both academic and commercial entities. Microfluidic, lung-mimic, and lung slice cultures have the advantages of cost-efficiency and high throughput analyses ideal for pharmaceutical and toxicity studies. Perfused/ventilated rodent whole lung systems can be adapted for mid-throughput studies of lung stem/progenitor cell development, cell behavior, understanding and treating lung injury, and for preliminary work that can be translated to human lung bioengineering. Human-sized ex vivo whole lung bioreactors incorporating perfusion and ventilation are amenable to automation and have been used for whole lung decellularization and recellularization. Clinical scale ex vivo lung perfusion systems have been developed for lung preservation and reconditioning and are currently being evaluated in clinical trials. Conclusions: Significant advances in bioreactors for lung engineering have been made at both the microfluidic and the macroscale. The most advanced are closed systems that incorporate pressure-controlled perfusion and ventilation and are amenable to automation. Ex vivo lung perfusion systems have advanced to clinical trials for lung preservation and reconditioning. The biggest challenges that lie ahead for lung bioengineering can only be overcome by future advances in technology that solve the problems of cell production and tissue incorporation.
Bibliographical noteFunding Information:
The author apologizes to investigators whose work was not cited in this review due to space limitations. However, many of those papers are cited in the reviews referenced here. The author thanks Ms. Kelsey Vigoren and Miss Marisa Mortari for help in preparing the manuscript. APM is partly funded by NHLBI R01HL108627 (?Overcoming Barriers to Bioengineering 3D Human Lung?). ? The computer program code for an automated lung bioreactor valve-control system is available for licensing from the University of Minnesota to commercial entities, but it is free and open-sourced for all academic investigators. Angela Panoskaltsis-Mortari is eligible to receive one ninth of any licensing fees. This article does not contain any studies with human or animal subjects performed by any of the authors.
The author apologizes to investigators whose work was not cited in this review due to space limitations. However, many of those papers are cited in the reviews referenced here. The author thanks Ms. Kelsey Vigoren and Miss Marisa Mortari for help in preparing the manuscript. APM is partly funded by NHLBI R01HL108627 (“Overcoming Barriers to Bioengineering 3D Human Lung”).
© 2015, Springer International Publishing AG.
- Tissue Engineering