Reconstruction of bone defects represents a serious issue for orthopaedic and maxillofacial surgeons, especially in extensive bone loss. Adipose-derived mesenchymal stem cells (ADScs) with tri-calcium phosphates (tcp) are widely used for bone regeneration facilitating the formation of bone extracellular matrix to promote reparative osteogenesis. The present study assessed the potential of cell-scaffold constructs for the regeneration of extensive mandibular bone defects in a minipig model. Sixteen skeletally mature miniature pigs were divided into two groups: Control group and scaffolds seeded with osteogenic differentiated pADSCs (n = 8/group). TCP-PLGA scaffolds with or without cells were integrated in the mandibular critical size defects and fixed by titanium osteosynthesis plates. After 12 weeks, ADSCs seeded scaffolds (n = 7) demonstrated significantly higher bone volume (34.8% ± 4.80%) than scaffolds implanted without cells (n = 6, 22.4% ± 9.85%) in the micro-CT (p < 0.05). Moreover, an increased amount of osteocalcin deposition was found in the test group in comparison to the control group (27.98 ± 2.81% vs 17.10 ± 3.57%, p < 0.001). In conclusion, ADSCs seeding on ceramic/polymer scaffolds improves bone regeneration in large mandibular defects. However, further improvement with regard to the osteogenic capacity is necessary to transfer this concept into clinical use. Maxillofacial bone defects, which occur due to trauma, craniofacial deformities, tumour or infection can lead to facial deformities and severe maxillofacial dysfunctions provoking a dramatic decrease in the quality of life of the patients 1,2. The reconstruction of large bone defects poses many challenges in oral and maxillofacial surgery. Although autologous bone grafts are considered the gold standard in bone defect repair, there are some concerns related to the limited supply and donor site morbidity 3. Several alternatives as allografts, xenografts or synthetic bone substitutes have been brought by researchers and clinicians to restore the function and architecture of the defective bone but still cannot solve the problem due to various limitations. The search of new treatment alternatives has emerged enormously in the past few