# Whole Organ Engineering: Approaches, Challenges, and Future Directions
## 5 Recent Developments and Accomplishments
### Gastrointestinal
The functionalization of an implanted engineered graft is highly promising; however, this protocol is suited towards relatively simpler organs comprised of thinner tissues and may not be able to be translated for engineering more complex whole organs with thicker, more solid tissue compositions. In this study, human-scale tissue-engineered lungs were created by perfusion decellularization of porcine whole lungs with SDS followed by Triton X-100. The vasculature of the lungs was then seeded with HUVECs by perfusion of cell suspension media through the pulmonary artery and vein. Epithelial cells were seeded into the bronchi in media suspension at a pressure of 80 mmHg followed by a period of perfusion culture through the pulmonary artery for 6 days to allow for endothelialization and epithelialization of the decellularized lung scaffold. The engineered lungs were then transplanted into adult pigs and evaluated for gas exchange and perfusion in vivo. The tissue-engineered lungs not only developed endothelialized vasculature and capillaries as well as a complete epithelium in the bronchial tubes, but the endothelial and epithelial cells rebuilt functional alveo in the decellularized ECM allowing for gas exchange to occur. While the capacity for gas exchange of the engineered lungs was about 50% of that of the native lung in the porcine model, this study is the first to successfully create a whole bioinformatic lung at a clinically relevant scale that recapitulates the function of the native lung in vivo. With further research, this technique could potentially produce clinically relevant bioartificial lungs for human transplant. [PERSON] et al. (2019). [PERSON] et al. (2019), demonstrated that focusing on preservation of GAGs when decellularizing kidneys can result in improved reendothelialization after infusions the kidneys with cells. They found that GAG preservation resulted in enhanced reendothelialization when coupled with preloading of growth factors, as the growth factors utilize GAGs to exert their effects. In addition, they developed a novel perfusion recellularization system that simultaneously infused acellular kidney scaffolds via the arteries and veins, which resulted in significantly improved endothelial covering of the vasculature by the infused endothelial cells derived from iPSCs. The methods presented in this publication were successfully used on both mouse and human cadaveric kidneys. As adequate endothelialization is vital for vasculature to function properly in organs, [PERSON] and colleagues’ work is a notable contribution to whole organ engineering. Their work in retaining specific ECM components during decellularization and developing a novel recellularization method, it translatable to other organs, would be a very useful protocol. \begin{table}
\begin{tabular}{c c} \hline \hline
**Year** & **Title** & **Number of Citations** & **Summary and Significance** \\ \hline \hline \multirow{9}{*}{2019} & \multicolumn{3}{c}{In 2017, [PERSON] and colleagues published their research on the successful engineering of intestinal grafts populated with human iPSCs, which, after 28 days of culturing, demonstrated intestine-specific functionality. Sections of intestine were perfusion decentralized and then recallularized using spheroids comprising human iPSCs, with these spheroids adhering to the scaffold and forming a functional epithelial barrier capable of transferring nutrients across itself. These functional intestine grafts were then implanted into mice, after which the epithelial layer formed further matured and continued to transfer glucose and fatty acid nutrients. The functionalization of an implanted engineered graft is highly promising; however, this protocol is suited towards relatively simpler organs comprised of thinner tissues and may not be able to be translated for engineering more complex whole organs with thicker, more solid tissue compositions. In this study, human-scale tissue-engineered lungs were created by perfusion decellularization of porcine whole lungs with SDS followed by Triton X-100.