The reconstruction of massive segmental mandibular bone defects (SMDs) remains challenging even to- day; the current gold standard in human clinics being vascularized bone transplantation (VBT). As alter- native to this onerous approach, bone tissue engineering strategies have been widely investigated. How- ever, they displayed limited clinical success, particularly in failing to address the essential problem of quick vascularization of the implant. Although routinely used in clinics, the insertion of intrinsic vascular- ization in bioengineered constructs for the rapid formation of a feeding angiosome remains uncommon. In a clinically relevant model (sheep), a custom calcium phosphate-based bioceramic soaked with au- tologous bone marrow and perfused by an arteriovenous loop was tested to regenerate a massive SMD and was compared to VBT (clinical standard). Animals did not support well the VBT treatment, and the study was aborted 2 weeks after surgery due to ethical and animal welfare considerations. SMD regen- eration was successful with the custom vascularized bone construct. Implants were well osseointegrated and vascularized after only 3 months of implantation and totally entrapped in lamellar bone after 12 months; a healthy yellow bone marrow filled the remaining space.