Whole Organ Engineering: Approaches, Challenges, and Future Directions

End-stage organ failure remains a leading cause of morbidity and mortality across the globe. The only curative treatment option currently available for patients diagnosed with end-stage organ failure is organ transplantation. However, due to a critical shortage of organs, only a fraction of these patients are able to receive a viable organ transplantation. Those patients fortunate enough to receive a transplant must then be subjected to a lifelong regimen of immunosuppressant drugs. The concept of whole organ engineering offers a promising alternative to organ transplantation that overcomes these limitations. Organ engineering is a discipline that merges developmental biology, anatomy, physiology, and cellular interactions with enabling technologies such as advanced biomaterials and biofabrication to create bioartificial organs that recapitulate native organs in vivo. There have been numerous developments in bioengineering of whole organs over the past two decades. Key technological advancements include (1) methods of whole organ decellularization and recellularization, (2) three-dimensional bioprinting, (3) advanced stem cell technologies, and (4) the ability to genetically modify tissues and cells. These advancements give hope that organ engineering will become a commercial reality in the next decade. In this review article, we describe the foundational principles of whole organ engineering, discuss key technological advances, and provide an overview of current limitations and future directions.