# Whole Organ Engineering: Approaches, Challenges, and Future Directions
## 8 Conclusions  
There has been significant interest in the fields of whole organ engineering, tissue engineering, and regenerative medicine over the past few decades. This has been especially true because of the fact that end-stage organ failure continues to be a leading cause of morbidity and mortality around the world. Orthotopic organ transplantation is currently the only curative treatment option available for patients diagnosed with end-stage organ failure. However, significant advances in bioengineering of whole organ constructions continue to advance at a rapid pace, giving hope to those awaiting transplantation. Whole organ engineering has been supported by key technological advancements over the past few decades. These 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. However, several barriers to commercialization are still major obstacles that need to be systematically addressed. Engineering whole organ constructs with adequate cell populations is a significant technical barrier, as it is currently highly challenging to create an engineered organ with a homogenous cell density close to the high cell density that native organs possess. To address this barrier, stem cell research must be developed to improve cell invasion and adhesion of organ constructs. In addition to improving density of cells incorporated into engineered whole organs, the diversity of cells used must also be improved to better mimic the cell diversity found in native organ tissue. Though whole organ de-cell/re-cell approaches and cell bioprinting approaches have demonstrated the ability to incorporate multiple cell types into engineered organ constructs, this is often for the purpose of replicating but a single part of an organ's function, rather than replicating the entirety of the organ's functions. Also, though the variety of approaches to stem cell culture and differentiation, whole organ recellularization and decellularization, bioprinting, and genetic modification techniques being developed is conducive for research purposes, standardization is vital for clinical implementation of these techniques. Standardization necessitates the comparison of various methods in comprehensive studies for identifying the safest and most effective approaches to engineering whole organs, as demonstrated by multiple studies performed by different research groups. As the ultimate goal of whole organ engineering is clinical translation and transplantation, these standardized protocols would have to undergo strict regulatory examination. Regulatory pathways are an additional challenge facing the utilization of engineered whole organs as viable transplants and are principal among the non-technical barriers to commercial implementation. This is an important challenge, as regulatory pathways ensure that novel medical technologies can only be used commercially if they can properly demonstrate safety, with all potential risks and their respective likelihood of occurring being documented. An additional challenge outside of developing transplantable whole organ technology is the manufacturing of said organ. Current approaches for engineering whole organs are very involved processes with low production volumes and no indication of the ability to maintain consistent quality on a commercial scale. As a result, current methods of whole organ engineering would not be able to make a difference in reducing the number of individuals that die from end-stage organ failure. As such, it is necessary to develop novel manufacturing techniques in parallel with ongoing whole organ engineering research. Despite the field of whole organ engineering being quite new, much attention in research has been focused on it and relevant technologies, such as stem cells developed with the goal of advancing whole organ engineering.