# Whole Organ Engineering: Approaches, Challenges, and Future Directions
## 5 Recent Developments and Accomplishments
### Gastrointestinal
Despite the significant amount of research needed to bring these whole organ therapies to clinical viability, one GI tract organ therapy that is extremely close to achieving this is tissue-engineered and sphincters for treating fecal incontinence (FI). A recent study published in Nature Scientific Reports by [PERSON] et al. created bioengineered and sphincters using smooth muscle cells and neural progenitor cells from gut biopsies that were seeded onto a ring-shaped collagen hydrogel [152]. The construct formed an innervated ring of smooth muscle cells that when surgically implanted into a non-human primate FI model, cured the condition within 3 to 4 weeks of the surgery [152]. \begin{table}
\begin{tabular}{c c c c} \hline \hline
**Year** & **Title** & **Number of Citations** & **Summary and Significance** \\ \hline \multirow{8}{*}{2010} & & & In this study, a whole porcine decellularized heart was obtained in less than ten hours using pulsatile retrograde aortic perfusion of various enzymes, detergents, and acid solutions. This decellularized heart not only maintained the ECM components and mechanical properties of a native heart but also supported the differentiation of chicken cardiomyocytes into sarcomeres. This study marked the first full-scale decellularization of a heart close to human proportions and paved the way to using decellularized hearts in preclinical and clinical studies for cardiac therapies. Additionally, the perfusion method used for decellularization of whole organs is superior to previous methods in maintaining the native ECM compositions and architecture and efficiently removing cells. As a result, this method has been adapted for decellularizing other organ types, advancing the entire field of whole organ engineering as a result. In this study, whole livers were engineered with functional vasculature by first using perfusion decellularization of detergents through the vascular network of the liver followed by perfusion of human fetal liver and endothelial cells through this vascular network. This resulted in the creation of whole livers in vitro seeded with human cells containing vasculature with fully formed endothelium and differentiated hepatic and epithelial tissues surrounding them. This study represents a significant advancement in whole organ engineering since many approaches lack the creation of functional vasculature, which is essential to support cell viability and tissue function, and struggle to both adequately decellularize large organs and recellularize them with the appropriate number of cells to create a functional engineered organ. This method overcomes those challenges by using the existing vascular network of the organ to both remove the cells, reellularize the organ, and form a new vascular network to support the organ. The influence of this study on the field of whole organ engineering is immense as it opens the door to clinical translation of engineered whole organs for organ repair and transplantation. \\ \hline \hline \end{tabular}
\end{table} 
Table 1: Summary of the most significant publications in the past decade. \begin{table}
\begin{tabular}{c c c} \hline \hline
**Year** & **Title** & **Number of Citations** & **Summary and Significance** \\ \hline \hline \multirow{9}{*}{2012} & \multirow{9}{*}{Decellularization Methods of Porcine Kidney for Whole Organ Engineering using a High-Throughput System [(Sullivan) [153]]} & In this study, whole porcine kidneys were decentralized with a high-throughput system that pumped detergents through the renal vasculature. The porcine cells were successfully cleared while maintaining the complex microvasculature of the kidneys as well as the native ECM structure and composition. The decellularized kidneys were then evaluated for cytotoxicity and the kidneys perfused with 0.5% SDS showed no significant difference in cell viability from tissue plastic controls.