There has been an ongoing quest for new biomedical materials for the repair and regeneration of large segmental bone defects caused by disease or trauma. Autologous bone graft (ABG) remains the gold standard for bone repair despite their limited supply and donor-site morbidity. The current tissue engineering approach with synthetically derived bone grafts requires a bioactive ceramic or polymeric scaffold loaded with growth factors for osteoinduction and angiogenesis, and bone marrow stromal cells (BMSCs) for osteogenic properties. Unfortunately, this approach has serious drawbacks: the low mechanical strength of scaffolds, the high cost of growth factors, and a lack of optimal strategies for growth-factor delivery. Here, it is shown that, for the first time, a synthetic material alone can repair large bone defects as efficiently as the gold standard ABG. Through the use of strong and resorbable bioactive glass scaffolds, complete bone healing, and defect bridging can be achieved in a rabbit femur segmental defect model without growth factors or BMSCs. New bone and blood vessel formation, in both inner and peripheral scaffolds, demonstrates the excellent osteoinductive and osteogenic properties of these scaffolds similar as ABG.