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Patients fortunate enough to receive a transplant are required to receive immunosuppressive therapies and can face transplant rejection. The emerging concept of organ engineering may offer a new hope for these patients. Researchers in the field of regenerative medicine and tissue engineering are using three\u2010dimensional whole organ scaffolds composed of allogeneic or xenogeneic extracellular matrix (ECM) for engineering functional tissue suitable for transplantation. Perfusion decellularization is an approach that generates native ECM scaffolds with intact 3D anatomical architecture and vasculature. Decellularized organs provide the ideal transplantable scaffold with all the necessary microstructure and extracellular cues for cell attachment, differentiation, vascularization, and function. The present manuscript will review the role of the ECM in normal development, the concept of ECM tissue specificity, and the effect of processing methods on eventual clinical outcomes. An overview of existing challenges and future directions will also be discussed. J. Cell. Physiol. 229: 984\u2013989, 2014. \u00a9 2013 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcp.24532","type":"journal-article","created":{"date-parts":[[2013,12,18]],"date-time":"2013-12-18T06:16:58Z","timestamp":1387347418000},"page":"984-989","source":"Crossref","is-referenced-by-count":109,"title":["Role of the Extracellular Matrix in Whole Organ Engineering"],"prefix":"10.1002","volume":"229","author":[{"given":"Denver M.","family":"Faulk","sequence":"first","affiliation":[{"name":"McGowan Institute for Regenerative Medicine University of Pittsburgh Pittsburgh Pennsylvania"},{"name":"Department of Bioengineering University of Pittsburgh Pittsburgh Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott A.","family":"Johnson","sequence":"additional","affiliation":[{"name":"McGowan Institute for Regenerative Medicine University of Pittsburgh Pittsburgh 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