Alternative approaches to functional organ replacement. Organ transplant is plagued by lack of available tissue, the short window of tissue viability prior to transplant and graft rejection after transplant. A new bioengineering approach promises to overcome many of these challenges in the near future. Donor tissue, such as liver (A), is decellularized (B) through a multistep process that leaves the extracellular matrix scaffold intact. The matrix is then repopulated with tissue-specific cells that are compatible to the patient - for example, by differentiating patient-derived iPS cells into hepatocytes. Resultant tissues can either be studied in culture to gain insight into tissue function (C) or used for transplant in the clinic (D). Since this approach capitalizes on the remaining matrix scaffold and removes donor cells, tissues that would normally be discarded due to viability issues can be salvaged. Further, scaffolds repopulated with cells derived from the patient are less likely to be rejected.