The treatment of critical sized bone defect remains a significant challenge in orthopedics. The objective of the study is to evaluate the effect of the combination of bone morphogenetic protein 2 (BMP2) expressing genetically engineered mesenchymal stem cells (MSCs) [MSCs engineered using a multimam vector， pAceMam1， an emerging gene delivery vector] and an osteoconductive scaffold [silica coated nanohydroxyapatite-gelatin reinforced with fibers] in enhancing bone regeneration in critical sized segmental defects. The scaffold with transfected MSCs showed significantly higher viability， proliferation and osteogenic differentiation in vitro. Further， this group augmented union and new bone formation in critical sized rat femoral segmental defect at 12?weeks when compared to control groups (scaffold with MSCs and scaffold alone). These data demonstrated that the MSCs engineered for transient expression of BMP2 can improve the repair of segmental defects， which paves an avenue for using pAceMam1 as a vector for bone tissue regeneration.