Whole organ decellularization - a tool for bioscaffold fabrication and organ bioengineering

Abstract

The use of synthetic and naturally-derived scaffolds for bioengineering of solid organs has been limited due to a lack of an integrated vascular network. Here, we describe fabrication of a bioscaffold system with intact vascular tree. Animal-donor organs and tissues, ranging in size up-to thirty centimeters, were perfused with decellularization solution to selectively remove the cellular component of the tissue and leave an intact extracellular matrix and vascular network. The vascular tree demonstrated sequential fluid flow through a central inlet vessel that branched into an extensive capillary bed and coalesced back into a single outlet vessel. In one example, the liver, we used central inlet vessels to perfuse human and animal liver cells through the bioscaffold to create a functional liver tissue construct in vitro. These results demonstrate a novel yet simple and scalable method to obtain whole organ vascularized bioscaffolds with potential for liver, kidney, pancreas, intestine and other organs' bioengineering. These bioscaffolds can further provide a tool to study cells in their natural three-dimensional environment, which is superior for drug discovery platform compared with cells cultured in two-dimensional petri dishes.

Light-emitting diode effects on combined decellularization of tracheae. A novel approach to obtain biological scaffolds

“…Triton x100 is less harmful to glycosaminoglycans when compared to the other decellularization agents 26,27 . In our experiments, the apparent destruction of the remaining extracellular matrix seen at Figure 4 (C,E,F) are not due to the detergent exposure, but a histological processing artifact.…”

Liver bioengineering

“…it experiences great interest since the introduction of whole liver acellular scaffolds generated by perfusion decellularization [1][2][3] . Nevertheless, the different strategies developed so far have failed to generate hepatic tissue in vitro bioequivalent to native liver tissue.…”

Liver Regeneration and Bioengineering - The Emergence of Whole Organ Scaffolds

“…This approach may have a tremendous potential for the field of organ bioengineering. We have recently used a similar perfusion decellularization technique to liver, pancreas, intestine and kidney generating decellularized organ scaffolds for organ bioengineering (64,65). These bioscaffolds preserve their tissue microarchitecture and an intact vascular network that can be readily used as a route for recellularization by perfusion of culture medium with different cell populations.…”