End-organ failure is one of the major healthcare challenges in the Western world. Yet, donor organ shortage and the need for immunosuppression limit the impact of transplantation. The regeneration of whole organs could theoretically overcome these hurdles. Early milestones have been met by combining stem and progenitor cells with increasingly complex scaffold materials and culture conditions. Because the native extracellular matrix (ECM) guides organ development, repair and physiologic regeneration, it provides a promising alternative to synthetic scaffolds and a foundation for regenerative efforts. Perfusion decellularization is a novel technology that generates native ECM scaffolds with intact 3D anatomical architecture and vasculature. This review summarizes achievements to date and discusses the role of native ECM scaffolds in organ regeneration.
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