# Whole Organ Engineering: Approaches, Challenges, and Future Directions
## 5 Recent Developments and Accomplishments
### Kidney  
Whole kidney engineering has been performed through both top-down and bottom-up approaches. As is the case when engineering other whole organs, the use of a decellularized cadaveric kidney is a widespread approach to top-down kidney engineering [106; 107; 108; 109]. Standard decellularization protocol utilizing SDS to remove cellular material is applicable to whole kidneys and is commonly used [106; 107; 108; 109]. In 2013, [PERSON] and colleagues demonstrated the potential for top-down engineered kidneys to help reduce the disparity between organ supply and waitlisted individuals by engineering viable renal scaffolds from discarded human kidneys [106]. Kidneys are generally discarded for anatomical anomalies like atrophy or hardening of the renal vasculature, inflammation, or cortical necrosis, as well as prolonged ischemic storage [106]. Using SDS perfusion decellularization protocols, discarded human kidneys were found to maintain their ECM structure, vascular patency, and biochemical properties [106]. This research demonstrates the potential for whole organ engineering to lessen the organ recipient/donor disparity using readily available resources. Repopulation of acellular cadaveric kidney scaffolds has been demonstrated as well [110; 47; 111]. [PERSON] et al., repopulated decellularized rat kidney constructs with human endothelial cells derived from iPSCs [111]. Endothelial cell infusion through the renal artery of the rat kidneys led to widespread, homogeneous distribution of endothelial cells along the inner walls of the vasculature [111]. Transmission and scanning electron microscopy revealed that fenestration only occurred in the glomerular capillaries, indicating that the rat ECM scaffold had modulated endothelial cell adhesion and phenotype [111]. These findings suggest that whole kidney engineering via a top-down approach can maintain kidney macro- and micro-structure and preserve biochemical properties of renal structures to direct cell adhesion and activity.  
Additive manufacturing methods for kidney engineering have been utilized as well, and are showing promise in being able to replicate the internal architecture of the kidney [112; 113; 114; 115]. [PERSON] et al. published results of a novel ECM-derived, photo-crosslinkable bioink they had developed [112]. The bioink was derived from porcine kidneys that were perfusion decellularized with SDS, Triton-X 100, and nuclease enzymes, with the acellular ECM scaffold then being solubilized with acid, and the solution then methacylated so that it could be photo-crosslinked using UV light [112]. Constructs were printed using the kidney-derived bioink with human kidney cells included, with the resulting printed constructs retaining structural properties of native kidney tissue, and the cells remaining viable over time and maturing [112]. More recently, [PERSON] et al. utilized the same kidney-derived bioink to print ECM constructs laden with human kidney cells and implanted them in nude rats [115]. The constructs remained viable for two months, with comparisons of the implant site at the two-month timepoint to earlier times revealing that new tubular structures formed in the tissue around the implant, with human kidney cell markers detected in these new structures [115]. Host renal progenitor cell recruitment was observed in tissue surrounding acellular constructs that were implanted as well [115].