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Whole-liver decellularization comprises the removal of the antigenic cellular content, while maintaining intact 3D extracellular matrix architecture and the complex native vascular cues. As a result, it challenges the classical hurdles of xenotransplantation and hypothetically allows the production of bioengineered human-size liver constructs. The associated technique and understanding of the determinants of successful application evolved rapidly during the last decade. In this chapter, the authors offer a comprehensive walk-through, starting from the simplicity of the concept to the complexity of clinical application. Avoiding repetition, the chapter covers the fundamentals and advances of decellularization, recellularization, ex vivo perfusion culture, and sterilization techniques. The interplay between the main pivots of whole-liver decellularization, namely intrinsic matrix potentials, immune response, and vasculature is described. An effort was made to dissect the hurdles facing the whole-liver decellularization approach and to highlight the gaps in current literature. The authors also offer insights about some critical concepts including intra-scaffold flow dynamics, gradient zonation, critical cell mass/density, mechano-sensitivity, substrate modifications, nondestructive analysis, and the surgeon’s perspective, together with the discussion of published in vivo trials and large-scale production parameters.

Whole-Liver Decellularization: Advances and Insights into Current Understanding