Tissue engineering approaches have recently been devised to repair large bone losses. Tissue engineering takes advantages of the combined use of cultured living cells and 3D scaffolds to deliver vital cells to the damaged site of the patient. Cultured bone marrow stromal cells (BMSCs) can be regarded as a mesenchymal progenitor/precursor cell population derived from adult stem cells. When implanted in immunodeficient mice, BMSCs combined with mineralized 3D scaffolds to form a primary bone tissue that is highly vascularized. We have used autologous BMSC/bioceramic composites to treat full-thickness gaps of tibial diaphysis in sheep. The healing process has been investigated. The sequence of events is as follows: (1) bone formation on the outer surface of the implant; (2) bone formation in the inner cylinder canal; (3) formation of fissures and cracks in the implant body; (4) bone formation in the bioceramic pores. Similar composites whose size and shape reflected each bone defect have been implanted at the lesion sites of three patients. External fixation was used. Patients have been followed for more than three years. The results obtained are very promising and we propose the use of culture-expanded osteoprogenitor cells in conjunction with hydroxyapatite bioceramics as a significant improvement in the repair of critical size long bone defects.