In addition, biopsy specimens of decellularized scaffolds were seeded with hepatoblastoma cells for cytotoxicity testing or implanted s.c. After several days of rinsing, decellularized liver samples were histologically analyzed. Porcine livers were cannulated via the hepatic artery, then perfused with PBS, followed by successive Triton X-100 and SDS solutions in saline buffer. The goal of this study was to scale up our rodent liver decellularization method to livers of a clinically relevant size. One approach combines cells with acellular scaffolds derived from animal tissue. The field of regenerative medicine promises alternative therapeutic approaches, including the potential to bioengineer replacement hepatic tissue. These goals can be reached by an interdisciplinary approach bringing together researcher from several Universities, Research Institute and small companies who master innovative technologies of bioconstruction.Liver disease affects millions of patients each year. All steps in the project will take into consideration GMP procedures. By the end of the 5-year project, we aim to provide a prototype of an external bioartificial liver to be used for phase I and II clinical studies as well as a prototype liver-on-chip device ready for use by pharmaceutical companies producing new drugs. Studies in microfluidic devices should also allow us to improve maturation of the liver bioconstruction thanks to fluid pressure and flow. Progress in the construction of functional liver organoids will be transposed to the construction of an external bioartificial liver for the temporary treatment of acute liver failure and in liver- on-chip microfluidic devices for the study of drug metabolism and predictive toxicology. Final assessment of the liver will be performed in an immunodeficient rat model of acute liver insufficiency. Taking into account the poor yield of mature human liver cells, most cells will be obtained from differentiation of pluripotent stem cells, either embryonic or induced, which are now well mastered by our teams. Function of the different constructs will be assessed in vitro by functional assays and in vivo after implantation in animal models, which will also favor a complete maturation of the construct. The different steps of bioconstruction will be modeled in silico. The integration step should lead to a functional complete vascularized transplantable liver with a bile duct. Liver organoids will be produced by bioprinting as sheets or spheroids, involvinghepatocytes, endothelial cells and cholangiocytes, or as liver buds obtained from stem cells.We will focus particularly on producing a functional biliary network which has been a missing element in all previous studies. ![]() Vascular and biliary networks will be produced by a mix of technologies comprising organotypic culture, micropatterning and stereolithography. In the present project, bioconstruction of the liver will be performed by the assembly of building blocks –liver organoids, vascular networks and biliary networks- built separately and then integrated into a scaffold. The goals of this project are to build an external bioartificial liver, a liver-on-chip as well as a bioengineered liver.
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