# Whole Organ Engineering: Approaches, Challenges, and Future Directions
## 5 Recent Developments and Accomplishments
### Gastrointestinal
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\begin{tabular}{p{142.3 pt} p{142.3 pt} p{142.3 pt}} \hline Year & Title & Number of Citations & Summary and Significance \\ \hline \hline \multicolumn{3}{c}{In this study, rat and sheep livers were decellularized through perfusion of either Triton X-100 + SDS or SDS-only detergents and then recellularized either by in vivo implantation into rats or in vitro through perfusion of cell suspension media through the hepatic vein of the decellularized constructs. The results of the study showed that decellularization using the Triton X-100 + SDS detergent showed superior removal of cells, maintenance of native ECM architecture, and retention of mechanical properties relative to native tissue. These decellularized whole organs were successfully resected with hepatocytes in vivo and in vitro. The in vitro reseeding resulted in a native liver-like cellular architecture infiltrating both the regions surrounding the vessels and the parenchyma. This study represents a significant advancement over previous de-cell-re-cell studies of whole livers, which were only able to recellularize the vasculature or areas immediately surrounding the vasculature, whereas this study developed a technique for decellularization that enabled cellular infiltration throughout the entire thickness of the construct. This is a major step towards clinical viability of engineered whole organs since many rely on perfusion recellularization approaches but have had limited success with seeding the entire organ due to the distorted morphology of the ECM resulting from using an SDS only method of decellularization. \\ \hline \hline \multicolumn{3}{c}{In this study, human hearts were decellularized using perfusion-decellularization to obtain human acellular cardiac scaffolds and whole heart scaffolds. Scaffolds derived from 2D and 3D slices of acellular human myocardium were seeded with iPSC derived cardiomyocytes in static culture conditions and formed contractile cardiac tissue after 4–7 and 7–10 days, respectively. Human whole heart scaffolds were partially seeded with iPSC-derived cardiomyocytes by injection into different regions of the left ventricle followed by coronary artery perfusion of media and left ventricle wall mechanical stimulation in a custom bioreactor. The resulting ventricle tissue showed 50% cellular repopulation and maintained 90% cell viability over the culture period. The tissue also demonstrated visible contractile function when electrically stimulated and produced measurable spontaneous contractions and ventricular pressures of 2.4 mmHg. While this study did not produce a fully functional engineered heart, it is the closest anyone has come to producing an engineered whole heart at the clinically relevant scale. Additionally, this study used iPSCs to recellularize the whole heart matrix, which can allow for the creation of a patient-specific organ by obtaining iPSCs from the transplant patients own tissues. The ability to create a patient-specific organ for an organ with such complexity and high metabolic demands as the heart makes this study is a major milestone in the field of whole organ engineering. More work is needed to develop this technique to produce engineered whole human hearts that are clinically relevant for transplantation. \\ \hline \hline \end{tabular}
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Table 1: _Cont._
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**Year** & **Title** & **Number of Citations** & **Summary and Significance** \\ \hline \hline \multirow{9}{*}{2017} & \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.