The need for organs and tissues to treat end-stage organ failure and debilitating musculoskeletal conditions is a huge health requirement for Europe. Current treatments include organ transplants, bone grafts and tissue engineering and regenerative medicine approaches. Significant hurdles and limitations exist with all approaches: shortage of organ donors leads to patient mortality, autogenous bone grafts are often associated with pain and morbidity and allogeneic bone grafts can fail to vascularize and remodel. Existing use of scaffolds, cells and growth factors can also be problematic with worrying complications of negative host response, remodelling and rejection. A highly skilled UK researcher (Dr. Lisa White) with extensive experience in supercritical fluids will join the world leader in extracellular matrix materials (Dr. Steve Badylak at the University of Pittsburgh, USA) to gain unique skills in decellularization to collaboratively address these issues. In a pioneering step, an innovative supercritical fluid decellularization (SFD) technology will be developed. This SFD process will be utilized to decellularize whole organs to provide functional biological scaffolds with vascular networks, providing promise for whole organ engineering. Application of the SFD technology to bone will produce a powerful ex vivo model that will be utilized to provide essential information on cell response and healing. Finally, this ground-breaking SFD technology will produce advanced biologically compatible scaffolds for the regeneration of complex musculoskeletal defects.