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Donor site morbidity and limited volume remain primary drawbacks of using bone graft from the iliac crest and an impetus for finding other sources of autologous bone-graft material. The Synthes Reamer/Irrigator/Aspirator (RIA) has been found to have value as an autologous bone-graft harvesting device. The purpose of this study was to compare the cellular and biochemical characteristics of bone grafts obtained with use of the RIA and from the iliac crest of the same patient.A prospective study was performed on a consecutive series of ten skeletally mature patients presenting for repair of nonunited tibial or femoral fractures. Graft material was harvested from both the iliac crest (in the standard fashion) and the medullary canal of the femur or tibia (with use of the RIA) of each patient. Portions of each autologous graft sample were assessed histologically and by genomewide transcriptional profiling for biochemical markers known to be expressed during fracture-healing.Principal-component analysis comparing the messenger RNA expression profiles in the RIA and iliac crest samples showed that the expression profile at each harvest site was unique and independent of patient, age, sex, or any identified comorbidity. Transcriptional analysis showed that the RIA samples had greater levels of expression of genes associated with vascular, skeletal, and hematopoietic tissues. Additionally, stem cell markers and growth factors that act early in the osteogenic cascade were more abundant in the RIA samples compared with the iliac crest samples.This is the first study to directly compare the histological and molecular profiles of bone grafts from reaming debris and the iliac crest of the same patient. The debris generated during intramedullary reaming, harvested with use of the RIA technique, and the bone graft harvested from the iliac crest possessed a similar transcriptional profile for genes known to act in the early stages of bone repair and formation. This suggests that reaming debris may be a viable alternative to iliac crest bone graft when autologous cancellous graft is needed.